Aging - Envejecimiento

TÍTULO / TITLE:   - Toward the Identification of Neurophysiological Biomarkers for Alzheimers Disease in Down Syndrome: A Potential Role for Cross-Frequency Phase-Amplitude Coupling Analysis

REVISTA / JOURNAL:    - Aging Dis. 2023 Apr 1;14(2):428-449. doi: 10.14336/AD.2022.0906.

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AUTORES / AUTHORS: - Daniella B Victorino et al.

INSTITUCIÓN / INSTITUTION: - Discipline of Neuroscience, Department of Neurology and Neurosurgery, Federal University of São Paulo / Paulista Medical School, São Paulo, SP, Brazil. 

RESUMEN / SUMMARY: - Cross-frequency coupling (CFC) mechanisms play a central role in brain activity. Pathophysiological mechanisms leading to many brain disorders, such as Alzheimers disease (AD), may produce unique patterns of brain activity detectable by electroencephalography (EEG). Identifying biomarkers for AD diagnosis is also an ambition among research teams working in Down syndrome (DS), given the increased susceptibility of people with DS to develop early-onset AD (DS-AD). Here, we review accumulating evidence that altered theta-gamma phase-amplitude coupling (PAC) may be one of the earliest EEG signatures of AD, and therefore may serve as an adjuvant tool for detecting cognitive decline in DS-AD. We suggest that this field of research could potentially provide clues to the biophysical mechanisms underlying cognitive dysfunction in DS-AD and generate opportunities for identifying EEG-based biomarkers with diagnostic and prognostic utility in DS-AD.

TÍTULO / TITLE:   - Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimers disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose

REVISTA / JOURNAL:    - Alzheimers Dement. 2023 May;19(5):2095-2116. doi: 10.1002/alz.12835. Epub 2022 Nov 12.

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AUTORES / AUTHORS: - Xu-Qiao Chen et al

INSTITUCIÓN / INSTITUTION: - Department of Neurosciences, University of California San Diego, La Jolla, California, USA. 

RESUMEN / SUMMARY: - Introduction: Synaptic failure, a hallmark of Alzheimers disease (AD), is correlated with reduced levels of synaptic proteins. Though people with Down syndrome (DS) are at markedly increased risk for AD (AD-DS), few studies have addressed synapse dysfunction. Methods: Synaptic proteins were measured in the frontal cortex of DS, AD-DS, sporadic AD cases, and controls. The same proteins were examined in the Dp16 model of DS. Results: A common subset of synaptic proteins were reduced in AD and AD-DS, but not in DS or a case of partial trisomy 21 lacking triplication of APP gene. Pointing to compromised synaptic function, the reductions in AD and AD-DS were correlated with reduced SNARE complexes. In Dp16 mice reductions in syntaxin 1A, SNAP25 and the SNARE complex recapitulated findings in AD-DS; reductions were impacted by both age and increased App gene dose. Discussion: Synaptic phenotypes shared between AD-DS and AD point to shared pathogenetic mechanisms.

TÍTULO / TITLE:   - Individualized estimated years from onset of Alzheimers disease- related decline for adults with Down syndrome

REVISTA / JOURNAL:    - Alzheimers Dement (Amst). 2023 Jun 27;15(2):e12444. doi: 10.1002/dad2.12444. eCollection 2023 Apr-J

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AUTORES / AUTHORS: - Wayne Silverman et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics University of California, Irvine Irvine California USA. 

RESUMEN / SUMMARY: - Introduction: Adults with Down syndrome (DS) are at increased risk for Alzheimers disease (AD) and vary in their age of transition from AD preclinical to prodromal or more advanced clinical stages. An empirically based method is needed to determine individual "estimated years from symptom onset (EYO)," the same construct used in studies of autosomal dominant AD . Methods: Archived data from a previous study of > 600 adults with DS were examined using survival analysis methods. Age-specific prevalence of prodromal AD or dementia, cumulative risk, and EYOs were determined. Results: Individualized EYOs for adults with DS ranging in age from 30 to 70+ were determined, dependent upon chronological age and clinical status. Discussion: EYOs can be a useful tool for studies focused on biomarker changes during AD progression in this and other populations at risk, studies that should contribute to improved methods for diagnosis, prediction of risk, and identification of promising treatment targets. Highlights: Years from Alzheimers disease (AD) onset (EYO) was estimated for adults with Down syndrome (DS).EYOs were informed by AD clinical status and age, ranging from 30 to > 70 years.Influences of biological sex and apolipoprotein E genotype on EYOs were examined. EYOs have advantages for predicting risk of AD-related dementia compared to age.EYOs can be extremely informative in studies of preclinical AD progression.

TÍTULO / TITLE:   - Astroglial and microglial pathology in Down syndrome: Focus on Alzheimers disease

REVISTA / JOURNAL:    - Front. Cell.Neurosci.20 Sept.2022 Sec.Non-Neurnl Cells Vol.16.2022 doi.org/10.3389/fncel.2022.987212

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AUTORES / AUTHORS: - Octavio García, Lisi Flores-Aguilar

INSTITUCIÓN / INSTITUTION: - Facultad de Psicologcía, Unidad de Investigación en Psicobiologcía y Neurociencias, Universidad Nacional Autónoma de México, Ciudad de México, Mexico 

RESUMEN / SUMMARY: - Down syndrome (DS) arises from the triplication of human chromosome 21 and is considered the most common genetic cause of intellectual disability. Glial cells, specifically astroglia and microglia, display pathological alterations that might contribute to DS neuropathological alterations. Further, in middle adulthood, people with DS develop clinical symptoms associated with premature aging and Alzheimers disease (AD). Overexpression of the amyloid precursor protein (APP) gene, encoded on chromosome 21, leads to increased amyloid-β (Aβ) levels and subsequent formation of Aβ plaques in the brains of individuals with DS. Amyloid-β deposition might contribute to astroglial and microglial reactivity, leading to neurotoxic effects and elevated secretion of inflammatory mediators. This review discusses evidence of astroglial and microglial alterations that might be associated with the AD continuum in DS.

TÍTULO / TITLE:   - Timing of Alzheimers Disease by Intellectual Disability Level in Down Syndrome

REVISTA / JOURNAL:    - J Alzheimers Dis. 2023 Jul 17. doi: 10.3233/JAD-230200. Online ahead of print.

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AUTORES / AUTHORS: - Sigan L Hartley et al

INSTITUCIÓN / INSTITUTION: - Waisman Center, University of Wisconsin-Madison, Madison, WI, USA 

RESUMEN / SUMMARY: - Background: Trisomy 21 causes Down syndrome (DS) and is a recognized cause of early-onset Alzheimers disease (AD). Objective: The current study sought to determine if premorbid intellectual disability level (ID) was associated with variability in age-trajectories of AD biomarkers and cognitive impairments. General linear mixed models compared the age-trajectory of the AD biomarkers PET Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type, APOE status, biological sex, and site. Methods: Analyses involved adults with DS from the Alzheimers Biomarkers Consortium-Down Syndrome. Participants completed measures of memory, mental status, and visuospatial ability. Premorbid ID level was based on IQ or mental age scores prior to dementia concerns. PET was acquired using [11C] PiB for Aβ, and [18F] AV-1451 for tau. Results: Cognitive data was available for 361 participants with a mean age of 45.22 (SD = 9.92) and PET biomarker data was available for 154 participants. There was not a significant effect of premorbid ID level by age on cognitive outcomes. There was not a significant effect of premorbid ID by age on PET Aβ or on tau PET. There was not a significant difference in age at time of study visit of those with mild cognitive impairment-DS or dementia by premorbid ID level. Conclusion: Findings provide robust evidence of a similar time course in AD trajectory across premorbid ID levels, laying the groundwork for the inclusion of individuals with DS with a variety of IQ levels in clinical AD trials.

TÍTULO / TITLE:   - Lysosomal dysfunction in Down syndrome and Alzheimer mouse models is caused by v-ATPase inhibition by Tyr682-phosphorylated APP βCTF

REVISTA / JOURNAL:    - Sci Adv. 2023 Jul 28;9(30):eadg1925. doi: 10.1126/sciadv.adg1925. Epub 2023 Jul 26. Free PMC articl

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AUTORES / AUTHORS: - Eunju Im et al

INSTITUCIÓN / INSTITUTION: - Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA 

RESUMEN / SUMMARY: - Lysosome dysfunction arises early and propels Alzheimers disease (AD). Herein, we show that amyloid precursor protein (APP), linked to early-onset AD in Down syndrome (DS), acts directly via its β-C-terminal fragment (βCTF) to disrupt lysosomal vacuolar (H+)-adenosine triphosphatase (v-ATPase) and acidification. In human DS fibroblasts, the phosphorylated 682YENPTY internalization motif of APP-βCTF binds selectively within a pocket of the v-ATPase V0a1 subunit cytoplasmic domain and competitively inhibits association of the V1 subcomplex of v-ATPase, thereby reducing its activity. Lowering APP-βCTF Tyr682 phosphorylation restores v-ATPase and lysosome function in DS fibroblasts and in vivo in brains of DS model mice. Notably, lowering APP-βCTF Tyr682 phosphorylation below normal constitutive levels boosts v-ATPase assembly and activity, suggesting that v-ATPase may also be modulated tonically by phospho-APP-βCTF. Elevated APP-βCTF Tyr682 phosphorylation in two mouse AD models similarly disrupts v-ATPase function. These findings offer previously unknown insight into the pathogenic mechanism underlying faulty lysosomes in all forms of AD.

TÍTULO / TITLE:   - Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: a longitudinal cohort study

REVISTA / JOURNAL:    - EBioMedicine. 2023 Apr;90:104547. doi: 10.1016/j.ebiom.2023.104547. Epub 2023 Mar 30.

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AUTORES / AUTHORS: - Laia Montoliu-Gaya et al.

INSTITUCIÓN / INSTITUTION: - Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. 

RESUMEN / SUMMARY: - Background: The diagnosis of symptomatic Alzheimers disease is a clinical challenge in adults with Down syndrome. Blood biomarkers would be of particular clinical importance in this population. The astrocytic Glial Fibrillary Acidic Protein (GFAP) is a marker of astrogliosis associated with amyloid pathology, but its longitudinal changes, association with other biomarkers and cognitive performance have not been studied in individuals with Down syndrome. Methods: We performed a three-centre study of adults with Down syndrome, autosomal dominant Alzheimers disease and euploid individuals enrolled in Hospital Sant Pau, Barcelona (Spain), Hospital Clinic, Barcelona (Spain) and Ludwig-Maximilians-Universität, Munich (Germany). Cerebrospinal fluid (CSF) and plasma GFAP concentrations were quantified using Simoa. A subset of participants had PET 18F-fluorodeoxyglucose, amyloid tracers and MRI measurements. Findings: This study included 997 individuals, 585 participants with Down syndrome, 61 Familial Alzheimers disease mutation carriers and 351 euploid individuals along the Alzheimers disease continuum, recruited between November 2008 and May 2022. Participants with Down syndrome were clinically classified at baseline as asymptomatic, prodromal Alzheimers disease and Alzheimers disease dementia. Plasma GFAP levels were significantly increased in prodromal and Alzheimers disease dementia compared to asymptomatic individuals and increased in parallel to CSF Aβ changes, ten years prior to amyloid PET positivity. Plasma GFAP presented the highest diagnostic performance to discriminate symptomatic from asymptomatic groups (AUC = 0.93, 95% CI 0.9-0.95) and its concentrations were significantly higher in progressors vs non-progressors (p < 0.001), showing an increase of 19.8% (11.8-33.0) per year in participants with dementia. Finally, plasma GFAP levels were highly correlated with cortical thinning and brain amyloid pathology. Interpretation: Our findings support the utili

TÍTULO / TITLE:   - Distinct Molecular Signatures of Amyloid-Beta and Tau in Alzheimers Disease Associated with Down Syndrome

REVISTA / JOURNAL:    - Int J Mol Sci. 2023 Jul 18;24(14):11596. doi: 10.3390/ijms241411596. Free PMC article

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AUTORES / AUTHORS: - Shojiro Ichimata et al

INSTITUCIÓN / INSTITUTION: - Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 2S8, Canada. 

RESUMEN / SUMMARY: - Limited comparative data exist on the molecular spectrum of amyloid-beta (Aβ) and tau deposition in individuals with Down syndrome (DS) and sporadic Alzheimers disease (sAD). We assessed Aβ and tau deposition severity in the temporal lobe and cerebellum of ten DS and ten sAD cases. Immunohistochemistry was performed using antibodies against eight different Aβ epitopes (6F/3D, Aβ38, Aβ39, Aβ40, Aβ42, Aβ43, pyroglutamate Aβ at third glutamic acid (AβNp3E), phosphorylated- (p-)Aβ at 8th serine (AβpSer8)), and six different pathological tau epitopes (p-Ser202/Thr205, p-Thr231, p-Ser396, Alz50, MC1, GT38). Findings were evaluated semi-quantitatively and quantitatively using digital pathology. DS cases had significantly higher neocortical parenchymal deposition (Aβ38, Aβ42, and AβpSer8), and cerebellar parenchymal deposition (Aβ40, Aβ42, AβNp3E, and AβpSer8) than sAD cases. Furthermore, DS cases had a significantly larger mean plaque size (6F/3D, Aβ42, AβNp3E) in the temporal lobe, and significantly greater deposition of cerebral and cerebellar Aβ42 than sAD cases in the quantitative analysis. Western blotting corroborated these findings. Regarding tau pathology, DS cases had significantly more severe cerebral tau deposition than sAD cases, especially in the white matter (p-Ser202/Thr205, p-Thr231, Alz50, and MC1). Greater total tau deposition in the white matter (p-Ser202/Thr205, p-Thr231, and Alz50) of DS cases was confirmed by quantitative analysis. Our data suggest that the Aβ and tau molecular signatures in DS are distinct from those in sAD.

TÍTULO / TITLE:   - Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels

REVISTA / JOURNAL:    - EBioMedicine. 2023 Jul 5;104692. doi: 10.1016/j.ebiom.2023.104692. Online ahead of print. Free arti

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AUTORES / AUTHORS: - Aoife Murray et al.

INSTITUCIÓN / INSTITUTION: - Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK; The London Down Syndrome Consortium (LonDownS), London, UK.  

RESUMEN / SUMMARY: - Background: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. Methods: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. Findings: Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. Interpretation: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies.

TÍTULO / TITLE:   - PCP4 Promotes Alzheimers Disease Pathogenesis by Affecting Amyloid-β Protein Precursor Processing

REVISTA / JOURNAL:    - J Alzheimers Dis. 2023;94(2):737-750. doi: 10.3233/JAD-230192.

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AUTORES / AUTHORS: - Dongjie Hu et al

INSTITUCIÓN / INSTITUTION: - Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Hea 

RESUMEN / SUMMARY: - Background: Down syndrome (DS) is caused by an extra copy of all or part of chromosome 21. The patients with DS develop typical Alzheimers disease (AD) neuropathology, indicating the role of genes on human chromosome 21 (HSA21) in the pathogenesis of AD. Purkinje cell protein 4 (PCP4), also known as brain-specific protein 19, is a critical gene located on HSA21. However, the role of PCP4 in DS and AD pathogenesis is not clear. Objective: To explore the role of PCP4 in amyloid-β protein precursor (AβPP) processing in AD. Methods: In this study, we investigated the role of PCP4 in AD progression in vitro and in vivo. In vitro experiments, we overexpressed PCP4 in human Swedish mutant AβPP stable expression or neural cell lines. In vitro experiments, APP23/PS45 double transgenic mice were selected and treated with AAV-PCP4. Multiple topics were detected by western blot, RT-PCR, immunohistochemical and behavioral test. Results: We found that PCP4 expression was altered in AD. PCP4 was overexpressed in APP23/PS45 transgenic mice and PCP4 affected the processing of AβPP. The production of amyloid-β protein (Aβ) was also promoted by PCP4. The upregulation of endogenous AβPP expression and the downregulation of ADAM10 were due to the transcriptional regulation of PCP4. In addition, PCP4 increased Aβ deposition and neural plaque formation in the brain, and exuberated learning and memory impairment in transgenic AD model mice. Conclusion: Our finding reveals that PCP4 contributes to the pathogenesis of AD by affecting AβPP processing and suggests PCP4 as a novel therapeutic target for AD by targeting Aβ pathology.

TÍTULO / TITLE:   - Diagnostic Sensitivity and Specificity of Cognitive Tests for Mild Cognitive Impairment and Alzheimers Disease in Patients with Down Syndrome: A Systematic Review and Meta-Analysis

REVISTA / JOURNAL:    - J Alzheimers Dis. 2023 Jul 25. doi: 10.3233/JAD-220991. Online ahead of print.

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AUTORES / AUTHORS: - Patricia A Nadeau et al

INSTITUCIÓN / INSTITUTION: - Univerisité de Montréal, Quebec, Canada 

RESUMEN / SUMMARY: - Background: Improved health care for people with Down syndrome (DS) has resulted in an increase in their life expectancy therefore increasing comorbidities associated with age-related problems in this population, the most frequent being Alzheimers disease (AD). To date, several cognitive tests have been developed to evaluate cognitive changes related to the development of mild cognitive impairment (MCI) and AD in people with DS. Objective: Identify and evaluate available cognitive tests for the diagnosis of MCI and AD in people with DS. Methods: A systematic search of the Pubmed and PsycInfo databases was performed to identify articles published from January 1, 2000 and July 1, 2022. Keysearch terms were DS, AD or MCI, cognition, and assessment. Relevant studies assessing the diagnostic accuracy of cognitive tests for AD or MCI with standard clinical evaluation were extracted. Risk of bias was assessed using the QUADAS 2. Results: We identified 15 batteries, 2 intelligence scales, 14 memory tests, 11 executive, functioning tests, 11 motor and visuospatial functioning tests, 5 language tests, 3 attention tests, and 2 orientation tests. Analysis showed that the CAMCOG-DS present a fair to excellent diagnostic accuracy for detecting AD in patients with DS. However, for the diagnosis of MCI, this battery showed poor to good diagnostic accuracy. Conclusion: The findings highlight important limitations of the current assessment available for the screening of mild cognitive impairment and AD in patients with DS and support the need for more clinical trials to ensure better screening for this highly at-risk population.

TÍTULO / TITLE:   - Modeling Alzheimers disease related phenotypes in the Ts65Dn mouse: impact of age on Aβ, Tau, pTau, NfL, and behavior

REVISTA / JOURNAL:    - Front Neurosci. 2023 Jun 28;17:1202208. doi: 10.3389/fnins.2023.1202208. eCollection 2023. Free PMC

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AUTORES / AUTHORS: - Cassia Overk et al

INSTITUCIÓN / INSTITUTION: - Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States 

RESUMEN / SUMMARY: - Introduction: People with DS are highly predisposed to Alzheimers disease (AD) and demonstrate very similar clinical and pathological features. Ts65Dn mice are widely used and serve as the best-characterized animal model of DS. Methods: We undertook studies to characterize age-related changes for AD-relevant markers linked to Aβ, Tau, and phospho-Tau, axonal structure, inflammation, and behavior. Results: We found age related changes in both Ts65Dn and 2N mice. Relative to 2N mice, Ts65Dn mice showed consistent increases in Aβ40, insoluble phospho-Tau, and neurofilament light protein. These changes were correlated with deficits in learning and memory. Discussion: These data have implications for planning future experiments aimed at preventing disease-related phenotypes and biomarkers. Interventions should be planned to address specific manifestations using treatments and treatment durations adequate to engage targets to prevent the emergence of phenotypes.

Cardiology - Cardiología

TÍTULO / TITLE:   - Interferon hyperactivity impairs cardiogenesis in Down syndrome via downregulation of canonical Wnt signaling

REVISTA / JOURNAL:    - iScience. 2023 Jun 5;26(7):107012. doi: 10.1016/j.isci.2023.107012. eCollection 2023 Jul 21.

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AUTORES / AUTHORS: - Congwu Chi et al

INSTITUCIÓN / INSTITUTION: - Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus; Aurora, CO 80045, USA. 

RESUMEN / SUMMARY: - Congenital heart defects (CHDs) are frequent in children with Down syndrome (DS), caused by trisomy of chromosome 21. However, the underlying mechanisms are poorly understood. Here, using a human-induced pluripotent stem cell (iPSC)-based model and the Dp(16)1Yey/+ (Dp16) mouse model of DS, we identified downregulation of canonical Wnt signaling downstream of increased dosage of interferon (IFN) receptors (IFNRs) genes on chromosome 21 as a causative factor of cardiogenic dysregulation in DS. We differentiated human iPSCs derived from individuals with DS and CHDs, and healthy euploid controls into cardiac cells. We observed that T21 upregulates IFN signaling, downregulates the canonical WNT pathway, and impairs cardiac differentiation. Furthermore, genetic and pharmacological normalization of IFN signaling restored canonical WNT signaling and rescued defects in cardiogenesis in DS in vitro and in vivo. Our findings provide insights into mechanisms underlying abnormal cardiogenesis in DS, ultimately aiding the development of therapeutic strategies.

TÍTULO / TITLE:   - Cytogenetic study of subtypes of Down syndrome and its relation with pattern of congenital cardiac defects

REVISTA / JOURNAL:    - J Pak Med Assoc. 2023 Feb;73(2):270-274. doi: 10.47391/JPMA.5422.

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AUTORES / AUTHORS: - Areiba Haider et al

INSTITUCIÓN / INSTITUTION: - Department of Anatomy, King Edward Medical University, Lahore, Pakistan. 

RESUMEN / SUMMARY: - Objective: To determine the frequency of subtypes of Down syndrome by karyotyping, and to establish the frequency of congenital cardiac defects in this population. Methods: The cross-sectional study was conducted at the Department of Genetics, Children Hospital, Lahore, Pakistan, from June 2016 to June 2017, and comprised of Down Syndrome patients aged <15 years. They were subjected to karyotypic analysis for determining the subtype of the syndrome, and echocardiography of all cases was done for the assessment of congenital cardiac defects. The two findings was subsequently used to establish a relation between the subtypes and congenital cardiac defects. Data collected, entered and analyzed by the SPSS version 20.0. Results: Among the 160 cases, trisomy 21 was found in 154(96.2%), translocation 5(3.1%) and mosaicism 1(0.6%). Overall, 63(39.4%) children had cardiac defects. Among such patients, patent ductus arteriosus was most common 25(39.7%), followed by ventricular septal defects24(38.1%), atrial septal defects16(25.4%), complete atrioventricular septal defects 8(12.7%), and Tetralogy of Fallot3(4.8%), while 6(9.5%) children had other defects. Atrial septal defects was the most common double defect 9(56.2%) and had the highest coexistence with patent ductus arteriosus in Down syndrome cases with congenital cardiac defects. Conclusions: In Trisomy 21, the most common cardiac defect was patent ductus arteriosus, followed by ventricular septal defects in isolated defects, whereas in mixed defects, atrial septal defects and patent ductus arteriosus were the highest.

TÍTULO / TITLE:   - Creation of iPSC line NCHi004-A from a patient with down syndrome and congenital heart defects

REVISTA / JOURNAL:    - Stem Cell Res. 2023 Jun 24;71:103156. doi: 10.1016/j.scr.2023.103156. Online ahead of print.

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AUTORES / AUTHORS: - Matthew Alonzo et al

INSTITUCIÓN / INSTITUTION: - Center for Cardiovascular Research, Abigail Wexner Research Institute, Nationwide Childrens Hospital, Columbus, OH, USA; The Heart Center, Nationwide Childrens Hospital, Columbus, OH, USA. 

RESUMEN / SUMMARY: - Down syndrome is a congenital disorder resulting from an extra full or partial chromosome 21, which is characterized by a spectrum of systemic developmental abnormalities, including those affecting the cardiovascular system. Here, we generated an iPSC line from peripheral blood mononuclear cells of a male adolescent with Down syndrome-associated congenital heart defects through Sendai virus-mediated transfection of 4 Yamanaka factors. This line exhibited normal morphology, expressed pluripotency markers, trisomy 21 karyotype, and could be differentiated into three germ layers. This iPSC line can be used for studying cellular and developmental etiologies of congenital heart defects induced by aneuploidy of chromosome 21.

TÍTULO / TITLE:   - Transcatheter Edge-to-Edge Repair for Left Atrioventricular Valve Cleft After Previously Repaired Complete Atrioventricular Canal Defect in Down Syndrome

REVISTA / JOURNAL:    - CASE (Phila). 2022 Nov 9;7(1):35-38. doi: 10.1016/j.case.2022.09.008. eCollection 2023 Jan. Free PM

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AUTORES / AUTHORS: - Rohit Mital et al

INSTITUCIÓN / INSTITUTION: - Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, Arizona. 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Congenital Heart Defects and Outcome in a Large Cohort of Down Syndrome: A Single-Center Experience from Turkey

REVISTA / JOURNAL:    - Turk Arch Pediatr. 2023 Aug 3. doi: 10.5152/TurkArchPediatr.2023.23041. Online ahead of print.

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AUTORES / AUTHORS: - Dilek Uludağ Alkaya et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Genetics, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul, Turkey. 

RESUMEN / SUMMARY: - Objective: Congenital heart defects occur in approximately 50% of children with Down syndrome and they contribute considerably to morbidity and mortality. The aim of this study is to investigate the prevalence, classification, and survival of congenital heart defects in Down syndrome. Materials and methods: About 1731 Down syndrome patients who underwent echocardiography between 1986 and 2022 were evaluated. The median follow-up duration was 8.7 years (range 1-35.8 years). Congenital heart defect was grouped as cyanotic and acyanotic. Results: Among the 1731 patients, 52.1% had congenital heart defects. Congenital heart defect was significantly more common in females than males. The most common cardiac defect was ventricular septal defect (35%), followed by atrial septal defect (31.8%), atrioventricular septal defect (23.4%), tetralogy of Fallot (5%), and patent ductus arteriosus (3.6%). In the follow-up, 43.2% of atrial septal defect, 17.8% of ventricular septal defect, and a total of 20% of congenital heart defects were closed spontaneously. About 34.4% of congenital heart defect was corrected by cardiac surgery/intervention. Five-year survival rate was 97.4% in patients without congenital heart defects, whereas it was 95.6% in mild congenital heart defects and 86.1% in moderate to severe congenital heart defects. There was no relationship between consanguinity, parental age, maternal disease, folic acid supplementation before/during pregnancy, gestational age, birth weight, and congenital heart defects. Neuromotor development was similar in patients with and without congenital heart defects. Conclusion: We demonstrated that almost half of the patients had congenital heart defects; ventricular septal defect was the most common congenital heart defect type. This study is valuable in terms of the largest single-center study describing the classification, prognostic factors, and survival of Down syndrome patients with congenital heart defect from Turkey.

TÍTULO / TITLE:   - Pulmonary arterial hypertension in children with congenital heart disease: a deeper look into the role of endothelial progenitor cells and circulating endothelial cells to assess disease severity

REVISTA / JOURNAL:    - Front Pediatr. 2023 Jul 6;11:1200395. doi: 10.3389/fped.2023.1200395. eCollection 2023.

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AUTORES / AUTHORS: - Juan Calder�n-Colmenero et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Cardiology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico 

RESUMEN / SUMMARY: - Endothelial progenitor cells and circulating endothelial cells have been proposed as useful markers of severity and disease progression in certain vascular diseases, including pulmonary arterial hypertension. Our study focused on evaluating the levels of circulating endothelial progenitor cells and circulating endothelial cells in patients with congenital left-to-right shunts and pulmonary hypertension undergoing definitive repair. Endothelial progenitor cells (identified by simultaneous co-expression of CD45dim, CD34 + and KDR2 + surface antibodies) and circulating endothelial cells (identified by simultaneous co-expression of inherent antibodies CD45-, CD31+, CD146 + and CD105+) were prospectively measured in seventy-four children (including children with Down syndrome), median age six years (2.75-10), with clinically significant left-to-right shunts undergoing transcatheter or surgical repair and compared to thirty healthy controls. Endothelial progenitor cells and, particularly, circulating endothelial cells were significantly higher in children with heart disease and pulmonary arterial hypertension when compared to controls. Endothelial progenitor cells showed significant correlation with pulmonary vascular resistance index when measured both systemically (r = 0.259; p = 0.026) and in the superior vena cava (r = 0.302; p = 0.009). Children with Down syndrome showed a stronger correlation between systemic cellularity and pulmonary vascular resistance index (r = 0.829; p = 0.002). Endothelial progenitor cells were reduced along their transit through the lung, whereas circulating endothelial cells did not suffer any modification across the pulmonary circulation. In children with yet to be repaired left-to-right shunts, endothelial progenitor cells and circulating endothelial cell counts are increased compared to healthy subjects.

Dental - Dental

TÍTULO / TITLE:   - Sella Turcica Morphometrics in Subjects with Down Syndrome

REVISTA / JOURNAL:    - J Stomatol Oral Maxillofac Surg. 2023 Jul 11;101559. doi: 10.1016/j.jormas.2023.101559. Online a

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AUTORES / AUTHORS: - Petros Papaefthymiou, Elvan Onem Ozbilen

INSTITUCIÓN / INSTITUTION: - School of Dentistry, Department of Orthodontics, Marmara University, Istanbul, Turkey. 

RESUMEN / SUMMARY: - Objective: Since the number of patients diagnosed with Down syndrome seeking orthodontic treatment is increasing, clinicians could contribute by applying diagnostic modalities used frequently in the orthodontic field for research purposes. Thus, The aim of the present study is to implement morphometric methods to investigate the size and shape of sella turcica in subjects with Down syndrome. Materials and methods: In this retrospective study, archive records of 24 individuals with Down syndrome were compared to 48 healthy controls matched for age and gender. Parameters such as sella anterior, midpoint, and posterior height were measured, as well as sella width, area, and length were calculated. Independent sample t-tests were applied for the comparison of differences in sella turcica dimensions. Geometric morphometric analysis of the sella was performed with, implementing methods such as Procrustes superimposition and principal component analysis. Statistical significance was set at p<0.05. Results: Statistically significant differences were found for sella anterior height, sella midpoint height, sella posterior height, sella maximum height, sella length, and sella area. All the aforementioned values were significantly increased in the Down syndrome subjects (p<0.05). Principal component analysis (PCA) depicted a statistically significant difference in sella shape between patients with Down syndrome and healthy controls (p<0.05). Conclusions: Subjects with Down syndrome presented significantly increased sella turcica dimensions as well statistically significant differences in shape compared to healthy controls.

TÍTULO / TITLE:   - Prevalence of Bruxism in Down Syndrome Patients: A Systematic Review and Metanalysis

REVISTA / JOURNAL:    - J Oral Rehabil. 2023 Jul 28. doi: 10.1111/joor.13563. Online ahead of print.

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AUTORES / AUTHORS: - Mohammad Khursheed Alam et al.

INSTITUCIÓN / INSTITUTION: - Preventive Dentistry Department, College of Dentistry, Jouf University, Sakaka, Saudi Arabia 

RESUMEN / SUMMARY: - Bruxism is a parafunctional activity characterized by grinding or clenching of teeth and is a common oral health concern in individuals with Down syndrome (DS). Understanding the prevalence of bruxism in this population is crucial for developing effective management strategies. This systematic review and meta-analysis is aimed to investigate the prevalence of bruxism among individuals with DS and explore its association with other oral health issues; METHODS: A comprehensive search was conducted across multiple electronic databases to identify relevant studies. Cross-sectional and observational studies were included. Data on bruxism prevalence and associated factors were extracted, and a meta-analysis was performed using both fixed and random-effects models of MedCalc software. Heterogeneity among studies was assessed using I2 statistics. New Castle - Ottawa scale was used to evaluate methodological quality of the included studies RESULTS: Eight studies met the predefined inclusion criteria and were included in the analysis. Seven studies used a questionnaire to assess bruxism. The pooled proportion estimate for occurrence of Downs syndrome across the included studies was found to be 0.33 (95% CI: 0.22-0.45) as per the RE model and 0.35(95% CI: 0.31-0.450) as per FE model in the quantitative analysis. All studies exhibited good methodological quality CONCLUSION: This systematic review and meta-analysis provide evidence of a significant prevalence of bruxism among individuals with Down syndrome. The findings highlight the association of bruxism with other oral health issues and specific chromosomal abnormalities. Comprehensive oral health assessments, including diagnostic procedures like PSG, are essential for addressing the unique oral health needs of individuals with DS. Further studies are recommended with a valid tool for the diagnosis. Early interventions and management strategies need to be tailored to this population, considering the multifaceted nature of ora

TÍTULO / TITLE:   - A Comparative Evaluation of Physical Parameters of Saliva and Correlation with Periodontal Condition in Down Syndrome Children and Healthy Controls

REVISTA / JOURNAL:    - J Contemp Dent Pract. 2023 Jun 1;24(6):372-380. doi: 10.5005/jp-journals-10024-3481

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AUTORES / AUTHORS: - Hurlihal Sharath Chandra et al

INSTITUCIÓN / INSTITUTION: - Department of Paediatric and Preventive Dentistry, SJM Dental College and Hospital, PB Road, Chitradurga, Karnataka, India, Phone: +91 9743048418 

RESUMEN / SUMMARY: - Aim: The aim of this study was to assess the significance and role of physical parameters of saliva on periodontal health in children with Down syndrome (DS). Materials and methods: A comparative evaluation of physical parameters of saliva such as flow rate, viscosity, pH, quantity and buffering capacity, and buffer capacity was carried out using GC Saliva-Check Buffer kit and correlated with periodontal condition examined using community periodontal index of treatment needs (CPITN) in 40 DS subjects (group I) and 40 healthy controls (group II) aged 8-15 years. Results: Down syndrome subjects had a low resting salivary flow rate, moderately acidic saliva, very low quantity of stimulated saliva, and low buffering capacity. On correlating salivary parameters with the periodontal condition, DS subjects with CPITN code 1 had low resting salivary flow rate, normal viscosity, moderately acidic pH, very low quantity of stimulated saliva, and low buffering capacity. Down syndrome subjects with CPITN code 2 had low resting flow rate, increased viscosity, very low quantity of stimulated saliva, low buffering capacity, and moderately acidic pH. Healthy controls with CPITN code 0 had normal resting flow rate, viscosity of saliva, quantity of stimulated saliva, buffering capacity, and moderately acidic pH. Conclusion: Compared to healthy controls, DS subjects showed decreased values for resting flow rate, pH, quantity of stimulated saliva, and buffering capacity. A statistically significant correlation was observed between the physical parameters of saliva and periodontal condition in DS subjects (p < 0.05). Clinical significance: Periodontal diseases start at a very early age and periodontal health deteriorates at a faster rate in DS children for which saliva also plays its part. Prime importance should be given to frequent oral hygiene and preventive measures in DS children thus preventing accumulation of debris and plaque.

Dermatology - Dermatología

TÍTULO / TITLE:   - Treatment of Alopecia Universalis in a Child with Down Syndrome

REVISTA / JOURNAL:    - Indian J Pediatr. 2023 Aug 3. doi: 10.1007/s12098-023-04762-y. Online ahead of print.

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AUTORES / AUTHORS: - Evangeline Abenoja et al

INSTITUCIÓN / INSTITUTION: - Division of Dermatology, Sidra Medicine, Doha, Qatar 

RESUMEN / SUMMARY: -

Ear/Nasal - Otorrinolaringología

TÍTULO / TITLE:   - Down Syndrome for the Otolaryngologist: A Review

REVISTA / JOURNAL:    - JAMA Otolaryngol Head Neck Surg. 2023 Apr 1;149(4):360-367. doi: 10.1001/jamaoto.2023.0001

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AUTORES / AUTHORS: - Habib G Zalzal, Claire M Lawlor

INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology, Childrens National Medical Center, Washington, DC. 

RESUMEN / SUMMARY: - Importance: There are many features of Down syndrome that prompt referral to an otolaryngologist. As the lifetime prevalence and life expectancy of individuals with Down syndrome increase, it is increasingly likely that otolaryngologists will have the opportunity to care for patients with Down syndrome. Observations: A confluence of characteristics common to Down syndrome may be associated with issues in the head and neck, from infancy through adulthood. Hearing concerns range from narrow ear canals and cerumen impactions to eustachian tube dysfunction, middle ear effusion, cochlear malformations, and conductive, sensorineural, and/or mixed hearing loss. Immune deficiency, hypertrophy of Waldeyer ring, and hypoplastic sinuses may complicate and develop into chronic rhinosinusitis. Speech delay, obstructive sleep apnea, dysphagia, and airway anomalies are also common among this patient population. Because these concerns may necessitate otolaryngologic surgery, it is vital for otolaryngologists to familiarize themselves with anesthetic concerns, including cervical spine instability, in patients with Down syndrome. Comorbid cardiac disease, hypothyroidism, and obesity may also affect these patients and otolaryngologic care. Conclusions and relevance: Individuals with Down syndrome may visit otolaryngology practices at all ages. Otolaryngologists that familiarize themselves with the head and neck manifestations that are common among patients with Down syndrome and know when to order screening tests will be able to provide comprehensive care.

TÍTULO / TITLE:   - Association of Down syndrome with periodontal diseases: Systematic review and meta-analysis

REVISTA / JOURNAL:    - Spec Care Dentist. 2023 Jun 21. doi: 10.1111/scd.12892. Online ahead of print.

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AUTORES / AUTHORS: - Sara Rond�n-Avalo et al

INSTITUCIÓN / INSTITUTION: - Facultad de Odontología, Universidad de Antioquia, Medellín, Colombia. 

RESUMEN / SUMMARY: - Background: Down syndrome (DS) is distinguished by cognitive disability, a concave profile, and systemic complications. Oral diseases have been reported to be common in DS patients. Objective: To investigate the association between DS and periodontal diseases. Methods: Two independent reviewers searched six bibliographic databases up to January 2023 and used additional search methods to identify published studies on gingivitis or periodontitis in people with and without DS. Meta-analysis, risk of bias, sensibility analysis, publication bias, and evidence grading were all carried out. Results: Twenty-six studies were included for analysis. There was a tendency for increased plaque accumulation, periodontal probing, periodontal attachment level, bleeding on probing and indices in DS individuals. Meta-analysis of 11 studies showed a significant association between DS and periodontitis (OR 3.93; 95% CI 1.81-8.53). Probing depth was significantly high in individuals with DS as compared to controls (mean difference 0.40 mm; 95% CI 0.09-0.70). Gingivitis was significantly associated (OR 1.93; 95% CI 1.09-3.41) with DS in four studies. The evidence was classified as moderate certainty. Conclusion: Medium/low-quality studies demonstrate that Down syndrome is strongly associated with periodontitis and moderately associated with gingivitis.

TÍTULO / TITLE:   - What are the Soft Tissue Risk Factors for Obstructive Sleep Apnea in Patients with Downs Syndrome?

REVISTA / JOURNAL:    - Cleft Palate Craniofac J. 2023 Aug;60(8):986-992. doi: 10.1177/10556656221088171. Epub 2022 Mar 21

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AUTORES / AUTHORS: - Dani Stanbouly et al

INSTITUCIÓN / INSTITUTION: - Columbia University College of Dental Medicine, New York, NY, USA 

RESUMEN / SUMMARY: - Objective: To determine the risk factors and their respective magnitudes for developing Obstructive Sleep Apnea (OSA) in Down syndrome (DS) patients. Design: Retrospective cohort study. Patients: The 2016 Kids Inpatient Database (KID) was queried to identify all patients diagnosed with DS. Main outcome measures: The primary predictor variables were tonsillar hypertrophy (TH), adenoidal hypertrophy (AH), Hypertrophy of Tonsils & Adenoids (HTA), Laryngeal Stenosis (LS), Hypotonia, Glossoptosis, Congenital Laryngomalacia (CL), and Overweight & Obesity (OO). The primary outcome variable was OSA. Results: The final sample consisted of 18,181 patients with a diagnosis of DS. Relative to patients aged 0-5, patients aged 6-10 (OR 3.5, P < 0.01), 11-5 (OR 3.4, P < 0.01), and 16 & above (OR 3.6, P < 0.01) were each independently associated with increased odds of OSA. Further, TH (OR 23.2, P < 0.01), AH (OR 20.3, P < 0.01), HTA (OR 64.2, P < 0.01), glossoptosis (OR 5.0, P < 0.01), CL (OR 4.3, P < 0.01), and OO (OR 3.7, P < 0.01) were all independent risk factors for OSA. Conclusions: The presence of hypertrophied tonsils and adenoids together was the strongest risk factor for OSA. DS patients aged six and above were at risk for OSA development relative to younger patients. Patients with DS should be tested for OSA, which otherwise will deteriorate their existing comorbidities.

TÍTULO / TITLE:   - Otitis Media in Children with Down Syndrome Is Associated with Shifts in the Nasopharyngeal and Middle Ear Microbiotas

REVISTA / JOURNAL:    - Genet Test Mol Biomarkers. 2023 Jul;27(7):221-228. doi: 10.1089/gtmb.2023.0132.

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AUTORES / AUTHORS: - Christina L Elling et al

INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA 

RESUMEN / SUMMARY: - Background: Otitis media (OM) is defined as middle ear (ME) inflammation that is usually due to infection. Globally, OM is a leading cause of hearing loss and is the most frequently diagnosed disease in young children. For OM, pediatric patients with Down syndrome (DS) demonstrate higher incidence rates, greater severity, and poorer outcomes. However, to date, no studies have investigated the bacterial profiles of children with DS and OM. Method: We aimed to determine if there are differences in composition of bacterial profiles or the relative abundance of individual taxa within the ME and nasopharyngeal (NP) microbiotas of pediatric OM patients with DS (n = 11) compared with those without DS (n = 84). We sequenced the 16S rRNA genes and analyzed the sequence data for diversity indices and relative abundance of individual taxa. Results: Individuals with DS demonstrated increased biodiversity in their ME and NP microbiotas. In children with OM, DS was associated with increased biodiversity and higher relative abundance of specific taxa in the ME. Conclusion: Our findings suggest that dysbioses in the NP of DS children contributes to their increased susceptibility to OM compared with controls. These findings suggest that DS influences regulation of the mucosal microbiota and contributes to OM pathology.

Endocrinology/Nutrition - Endocrinología/Nutrición

TÍTULO / TITLE:   - Observations of feeding practices of US parents of young children with Down syndrome

REVISTA / JOURNAL:    - Matern Child Nutr. 2023 Jul 17;e13548. doi: 10.1111/mcn.13548. Online ahead of print.

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AUTORES / AUTHORS: - Victoria A Surette et al

INSTITUCIÓN / INSTITUTION: - School of Food Science, Washington State University, Pullman, Washington, USA. 

RESUMEN / SUMMARY: - Parental behaviours influence food acceptance in young children, but few studies have measured these behaviours using observational methods, especially among children with Down syndrome (CWDS). The overall goal of this study was to understand parent feeding practices used during snack time with young CWDS (N = 111, aged 11-58 months). A coding scheme was developed to focus on feeding practices used by parents of CWDS from a structured home-use test involving tasting variously textured snack products. Behavioural coding was used to categorise parental feeding practices and quantify their frequencies (N = 212 video feeding sessions). A feeding prompt was coded as successful if the child ate the target food product or completed the prompt within 20 s of the prompt being given without a refusal behaviour. CWDS more frequently consumed the test foods and completed tasks in response to Autonomy-Supportive Prompts to Eat (49.3%), than to Coercive-Controlling Prompts to Eat (24.2%). By exploring the parent-CWDS relationship during feeding, we can identify potentially desirable parent practices to encourage successful feeding for CWDS. Future research should build upon the knowledge gained from this study to confirm longitudinal associations of parent practices with child behaviours during feeding.

TÍTULO / TITLE:   - Selenium level correlates negatively with antibodies but positively with thyroid function in children with Down syndrome: an Indonesian study

REVISTA / JOURNAL:    - Front Endocrinol (Lausanne). 2023 May 10;14:1177373. doi: 10.3389/fendo.2023.1177373. eCollection 2

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AUTORES / AUTHORS: - Yuni Hisbiyah et al

INSTITUCIÓN / INSTITUTION: - Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia. 

RESUMEN / SUMMARY: - Background: Children with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Ses role in AITD in Indonesian children with DS. Methods: This cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann-Whitney, and Spearmans rank correlation (r s). All results with p<0.05 were considered statistically significant. Results: Among 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 and p=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (r s=-0.439 with p=1×10-5 and r s=-0.396 with p=0.001, respectively) and Tg-Ab (r s=-0.474 with p=1×10-5 and r s=-0.410 with p=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (r s=-0.252, p=0.048) in the AITD group. Conclusion: Selenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.

TÍTULO / TITLE:   - A call for obesity prevention interventions for young children with intellectual and developmental disabilities

REVISTA / JOURNAL:    - Transl Behav Med. 2023 Jul 13;ibad043. doi: 10.1093/tbm/ibad043. Online ahead of print.

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AUTORES / AUTHORS: - Michaela A Schenkelberg et al

INSTITUCIÓN / INSTITUTION: - School of Health & Kinesiology, University of Nebraska at Omaha, 6001 Dodge Street, H&K 207U, Omaha, NE 68182-0216, USA 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Prescriptions for insulin and insulin analogues in children with and without major congenital anomalies: a data linkage cohort study across six European regions

REVISTA / JOURNAL:    - Eur J Pediatr. 2023 May;182(5):2235-2244. doi: 10.1007/s00431-023-04885-6. Epub 2023 Mar 4.

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AUTORES / AUTHORS: - Joanne Given et al

INSTITUCIÓN / INSTITUTION: - Faculty of Life & Health Sciences, Ulster University, Belfast, Northern Ireland, UK. 

RESUMEN / SUMMARY: - Are children with major congenital anomalies more likely to develop diabetes requiring insulin therapy, as indicated by prescriptions for insulin, than children without congenital anomalies? The aim of this study is to evaluate prescription rates of insulin/insulin analogues in children aged 0-9 years with and without major congenital anomalies. A EUROlinkCAT data linkage cohort study, involving six population-based congenital anomaly registries in five countries. Data on children with major congenital anomalies (60,662) and children without congenital anomalies (1,722,912), the reference group, were linked to prescription records. Birth cohort and gestational age were examined. The mean follow-up for all children was 6.2 years. In children with congenital anomalies aged 0-3 years, 0.04 per 100 child-years (95% CIs 0.01-0.07) had > 1 prescription for insulin/insulin analogues compared with 0.03 (95% CIs 0.01-0.06) in reference children, increasing ten-fold by age 8-9 years. The risk of > 1 prescription for insulin/insulin analogues aged 0-9 years in children with non-chromosomal anomalies (RR 0.92, 95% CI 0.84-1.00) was similar to that of reference children. However, children with chromosomal anomalies (RR 2.37, 95% CI 1.91-2.96), and specifically children with Down syndrome (RR 3.44, 95% CIs 2.70-4.37), Down syndrome with congenital heart defects (RR 3.86, 95% CIs 2.88-5.16) and Down syndrome without congenital heart defects (RR 2.78, 95% CIs 1.82-4.27), had a significantly increased risk of > 1 prescription for insulin/insulin analogues aged 0-9 years compared to reference children. Female children had a reduced risk of > 1 prescription aged 0-9 years compared with male children (RR 0.76, 95% CI 0.64-0.90 for children with congenital anomalies and RR 0.90, 95% CI 0.87-0.93 for reference children). Children without congenital anomalies born preterm (< 37 weeks) were more likely to have > 1 insulin/insulin analogue prescription compared to term births (RR 1.28, 95%

TÍTULO / TITLE:   - Thyroid Function Tests in Children and Adolescents with Trisomy 21: Definition of Syndrome-Specific Reference Ranges

REVISTA / JOURNAL:    - J Clin Endocrinol Metab. 2023 Jun 3;dgad333. doi: 10.1210/clinem/dgad333. Online ahead of print.

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AUTORES / AUTHORS: - Alessandro Cattoni et al

INSTITUCIÓN / INSTITUTION: - Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy 

RESUMEN / SUMMARY: - Context: The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population. Objectives: a) to outline the age-dependent distribution of TFT among pediatric patients with DS; b) to describe the intraindividual variability of TFT over time; c) to assess the role of elevated TSH in predicting the future onset of overt hypothyroidism. Design: Retrospective, monocentric, observational analysis. Patients: We included 548 Down patients (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria: abnormal thyroid anatomy, treatments affecting TFT and positive thyroid auto-antibodies. Results: We determined the age-dependent distribution of TSH, FT3 and FT4 and outlined the relative nomograms for children with DS. Compared to non-syndromic patients, median TSH levels were statistically greater at any age (p < 0.001). Median FT3 and FT4 levels were statistically lower than controls (p < 0.001) only in specific age classes (0-11 for FT3, 11-18 years for FT4).TSH levels showed a remarkable fluctuation over time, with a poor (23-53%) agreement between the TSH centile classes at two sequential assessments.Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (NPP, 0.91), but poor positive (P) PV (0.15). Conclusions: By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3 and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.

TÍTULO / TITLE:   - Cardiometabolic risk in young adults with Down syndrome

REVISTA / JOURNAL:    - Am J Med Genet A. 2023 Jul;191(7):1758-1768. doi: 10.1002/ajmg.a.63197. Epub 2023 Mar 31.

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AUTORES / AUTHORS: - Jacquelyn Manfredo et al.

INSTITUCIÓN / INSTITUTION: - Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 

RESUMEN / SUMMARY: - Studies regarding cardiometabolic risk (CMR) for individuals with Down syndrome (DS) conflict. Our previous research in youth with DS, aged 10-20 years, found increased prevalence of dyslipidemia and prediabetes compared to matched peers without DS. Herein, we compare CMR in young adults with DS, aged 18-35 years, to a similar population-based sample from the 2001-2018 National Health and Nutrition Examination Survey (NHANES). The group with DS had higher NonHDL-C (mean DS 131.9 mg/dL; NHANES 126.1 p < 0.001), lower HDL-C (DS 47.5 mg/dL; NHANES 52.2 p < 0.001), higher LDL-C (DS 109.3 mg/dL; NHANES 105.4 p < 0.001), higher triglycerides (DS 102.9 mg/dL; NHANES 86.9 p < 0.001), but lower fasting glucose (DS 85.8 mg/dL; NHANES 95.2 p < 0.0001), lower HOMA-IR (DS 2.17; NHANES 2.24 p = 0.0006), lower systolic (DS 109.7 mmHg; NHANES 114.6 p < 0.0001) and lower diastolic (DS 60.9 mmHg; NHANES 67.8 p < 0.0001) blood pressures. There was relationship of higher HDL-C, triglycerides, glucose, systolic, and diastolic blood pressure with increasing BMI in the NHANES cohort which was dampened in the group with DS. These results indicate that more information is needed to guide clinicians in screening for CMR in individuals with DS.

TÍTULO / TITLE:   - Cytotoxic T-lymphocyte-associated protein 4 +49A/G polymorphism in Down syndrome children with Hashimotos thyroiditis

REVISTA / JOURNAL:    - Biomol Biomed. 2023 Jul 3;23(4):634-639. doi: 10.17305/bb.2022.7869. Free PMC article

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AUTORES / AUTHORS: - Muhammad Faizi et al

INSTITUCIÓN / INSTITUTION: - Faculty of Medicine, Department of Child Health, Dr. Soetomo General Hospital, Universitas Airlangga, Surabaya, East Java, Indonesia. 

RESUMEN / SUMMARY: - Thyroid dysfunction is the most common endocrine disorder in Down syndrome (DS) children. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is one of the immune regulatory genes that correlates with Hashimotos thyroiditis (HT). However, studies on CTLA-4 +49A/G in DS children with HT are still limited. We aimed to evaluate CTLA-4 +49A/G gene polymorphism in DS children with HT. This case-control study, conducted from February 2020 to February 2022 at Dr. Soetomo General Hospital, Surabaya, enrolled 40 DS children with HT and 50 healthy children. The DNA sequencing was performed to identify the polymorphism (Sanger sequencing). Thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). The mean age of DS children with HT was 1.78 years. Males predominated in the study population. Subjects with GG genotype were diagnosed earliest with hypothyroidism (8 months) compared with other studies. The most common thyroid dysfunction was central hypothyroidism, with TgAb positivity present in all patients. The AA genotype (odds ratio [OR] 0.265, 95% confidence interval [CI] 0.094-0.746; P = 0.012) and A allele (OR 0.472, 95% CI 0.309-0.721; P = 0.0002) were significantly more frequent in the control group. The AG genotype (OR 2.65, 95% CI 0.094-0.746; P = 0.003) and G allele (OR 2.116, 95% CI 1.386-3.23; P = 0.003) were more frequent in the DS with HT group. The age of the subjects in this study was younger than in previous studies. The AG genotype and the G allele were more prevalent in the DS with HT group and may be a risk factor in HT development in DS children. Furthermore, the AA genotype may act as a protective factor against HT in DS children.

TÍTULO / TITLE:   - Increased levels of anti-BSA antibodies in children with Down syndrome

REVISTA / JOURNAL:    - Front Endocrinol (Lausanne). 2023 Feb 3;14:1056925. doi: 10.3389/fendo.2023.1056925. eCollection

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AUTORES / AUTHORS: - Sian L Grace et al

INSTITUCIÓN / INSTITUTION: - Bristol Medical School, University of Bristol, Bristol, United Kingdom 

RESUMEN / SUMMARY: - Introduction: Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cows milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls. Methods: Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Barts Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP). Results: Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated. Conclusion: Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.

Gastroenterology - Gastroenterología

TÍTULO / TITLE:   - Dysphagia severity is associated with worse sleep-disordered breathing in infants with Down syndrome

REVISTA / JOURNAL:    - J Clin Sleep Med. 2023 May 1;19(5):883-887. doi: 10.5664/jcsm.10446.

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AUTORES / AUTHORS: - Yeilim Cho et al

INSTITUCIÓN / INSTITUTION: - Sleep Center, University of Washington, Seattle, Washington 

RESUMEN / SUMMARY: - Study objectives: Hypotonia, commonly seen in infants with Down syndrome (I-DS), can contribute to masticatory and oropharyngeal muscle weakness, increasing the risk for dysphagia and sleep-disordered breathing. Data describing the occurrence of dysphagia and sleep-disordered breathing in I-DS are limited. This study aims to determine the frequency and severity of dysphagia and its relationship to polysomnogram parameters in I-DS. Methods: We included I-DS who underwent polysomnography at a single academic center over a 6-year period. Data collected included sex, age, presence of dysphagia (low suspicion of dysphagia vs dysphagia vs feeding tube), and polysomnographic data. Dysphagia was determined by a video fluoroscopic swallow study in the presence of clinical suspicion. Results: A total of 40 I-DS were identified (mean age 6.6 months ± 3; male 65%). There were 11, 13, and 16 I-DS with low suspicion of dysphagia, dysphagia, and feeding tube, respectively. Obstructive sleep apnea was more severe in I-DS in the feeding tube group when compared with the group with a low suspicion of dysphagia and (apnea-hypopnea index mean [standard error] = 49.3 [7.6] vs 19.2 [9.2] events/h; P = .016). Dysphagia severity was positively correlated with a higher obstructive apnea-hypopnea index (r = .43, P = .006). Conclusions: There is a high incidence of dysphagia and sleep-disordered breathing in I-DS. Dysphagia severity correlated with obstructive apnea-hypopnea index severity. Our results suggest that I-DS need early evaluation of both sleep-disordered breathing and dysphagia.

TÍTULO / TITLE:   - Social Determinants of Health and Hirschsprung-associated Enterocolitis

REVISTA / JOURNAL:    - J Pediatr Surg. 2023 Aug;58(8):1458-1462. doi: 10.1016/j.jpedsurg.2022.09.039. Epub 2022 Sep 30.

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AUTORES / AUTHORS: - Maria E Knaus et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Colorectal and Pelvic Reconstruction, Nationwide Childrens Hospital, 700 Childrens Drive, Columbus, OH 43205, USA 

RESUMEN / SUMMARY: - Background: Hirschsprung-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in patients with Hirschsprung disease (HD). The objective of this study was to examine the association of social determinants of health (SDOH) with HAEC. Methods: A review of patients who underwent primary pull through for HD at our institution from 2014 to 2021 was performed. Clinical, surgical, and SDOH data were collected. HAEC was defined by an international scoring system. Categorical variables were analyzed via Fishers exact tests and continuous variables with Moods median tests. Results: One hundred patients were identified with 29 patients (29%) having at least one episode of HAEC during a median follow-up of 31 months (IQR: 11.7-55.7). Children who utilized public transportation for clinic visits, had one or more missed appointments, had any reported safety concerns, were involved with Child Protective Services, had parents/guardians who were not married, lived with people other than their immediate family, or had mothers who reported drug use or lack of prenatal care were found to have a higher likelihood of developing HAEC (p<0.04 for all). Age at HD diagnosis, age at pull through, operative approach, length of aganglionic colon, and Trisomy 21 were not significant predictors of HAEC. Conclusions: In our series of 100 patients undergoing primary pull through, there was a significant correlation of HAEC with several social determinants of health elements while anatomical and clinical factors were not associated with HAEC. Attention to social determinants of health and identifying high-risk patients may serve to prevent morbidity and mortality from HAEC.

TÍTULO / TITLE:   - Effect of trisomy 21 on long-term gastrointestinal outcomes in duodenal atresia

REVISTA / JOURNAL:    - Pediatr Surg Int. 2023 Jan 18;39(1):84. doi: 10.1007/s00383-022-05359-w.

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AUTORES / AUTHORS: - Anna Zrinyi et al

INSTITUCIÓN / INSTITUTION: - Department of Surgery, Division of Pediatric Surgery, University of Manitoba, and Childrens Hospital Research Institute of Manitoba, AE402-820 Sherbrook Street, Winnipeg, MB, R3A 1S1, Canada 

RESUMEN / SUMMARY: - Purpose: We aimed to determine if Trisomy 21 (T21) affected gastrointestinal outcomes for children with duodenal atresia (DA). Methods: We identified children born with DA between 1991 and 2017. Cases were divided into DA with T21 and DA without T21. Ten healthy controls per case were included. Esophageal, ulcerative, obstructive and stomach complaints were assessed. Risk ratios (RR), rate ratios (RaR) and Cox models were constructed. Analyses were performed for cases versus controls, and for T21 cases versus non-T21 cases. Results: DA cases totaled 52: 22 had T21 and 30 did not. There were 520 controls. DA cases had more gastrointestinal complaints than controls. T21 cases were at greater risk and frequency of esophageal disease than non-T21 cases (RR = 4.08, p = 0.002, RaR = 69.8, p < 0.001). T21 and non-T21 cases were equally likely to present with obstruction (RR = 0.91, p = 1), but T21 cases complained of obstructive symptoms less (RaR = 0.57, p = 0.003). T21 and non-T21 cases had the same risk of stomach diseases, but T21 cases complained more frequently (RaR = 6.20, p < 0.001). Cox models supported these observations. T21 did not affect ulcerative diseases. Conclusion: DA cases had more gastrointestinal problems than controls. T21 increased esophageal and gastric complaints in DA cases but did not affect ulcerative and obstructive complaints.

TÍTULO / TITLE:   - The Spectrum of Duodenal Histologic Findings in Patients With Trisomy 21: A Multicenter Study

REVISTA / JOURNAL:    - J Pediatr Gastroenterol Nutr. 2023 Aug 1;77(2):184-190. doi: 10.1097/MPG.0000000000003825. Epub 202

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AUTORES / AUTHORS: - Erin Alexander et al

INSTITUCIÓN / INSTITUTION: - Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic Childrens Center, Rochester, MN. USA 

RESUMEN / SUMMARY: - Objectives: Patients with Trisomy 21 (T21) commonly have gastrointestinal symptoms and diseases that prompt evaluation with esophagogastroduodenoscopy (EGD). Our objective is to characterize duodenal histological abnormalities in these patients when undergoing EGD. A secondary aim is to explore associations of histologic findings with different therapies. Methods: Patients 30 years old or younger with T21 who underwent EGD from 2000 to 2020 at 6 hospitals were included in this retrospective cohort study. Duodenal biopsies were categorized based on reported histopathology findings as normal or abnormal. Abnormal pathology reports were reviewed and categorized into villous atrophy (VA) and duodenitis without VA. The VA group was further categorized based on the presence or absence of celiac disease (CD). Results: We identified 836 patients with T21 who underwent EGD, 419 (50.1%) of whom had duodenal histologic abnormalities. At the time of the first (index) abnormal duodenal biopsy, 290 of 419 had VA and of those, 172 of 290 met CD diagnostic criteria, while 118 of 290 did not meet CD criteria (nonspecific VA). Among the patients with an abnormal biopsy, acid suppression at the time of the index biopsy was less common in patients with VA-CD compared to patients without VA or patients with nonspecific VA (12.2% vs 45.7% vs 44.9%). Conclusions: Half of the T21 patients in this cohort had abnormal duodenal biopsies including a subgroup with nonspecific VA. In this cohort, acid suppression use was more prevalent in patients with abnormalities other than CD.

TÍTULO / TITLE:   - Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model

REVISTA / JOURNAL:    - Nat Genet. 2023 Jun;55(6):1034-1047. doi: 10.1038/s41588-023-01399-7. Epub 2023 Jun 5. Free PMC art

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AUTORES / AUTHORS: - Katherine A Waugh et al

INSTITUCIÓN / INSTITUTION: - Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 

RESUMEN / SUMMARY: - Down syndrome (DS), the genetic condition caused by trisomy 21, is characterized by variable cognitive impairment, immune dysregulation, dysmorphogenesis and increased prevalence of diverse co-occurring conditions. The mechanisms by which trisomy 21 causes these effects remain largely unknown. We demonstrate that triplication of the interferon receptor (IFNR) gene cluster on chromosome 21 is necessary for multiple phenotypes in a mouse model of DS. Whole-blood transcriptome analysis demonstrated that IFNR overexpression associates with chronic interferon hyperactivity and inflammation in people with DS. To define the contribution of this locus to DS phenotypes, we used genome editing to correct its copy number in a mouse model of DS, which normalized antiviral responses, prevented heart malformations, ameliorated developmental delays, improved cognition and attenuated craniofacial anomalies. Triplication of the Ifnr locus modulates hallmarks of DS in mice, suggesting that trisomy 21 elicits an interferonopathy potentially amenable to therapeutic intervention.

Genetics - Genética

TÍTULO / TITLE:   - Interferon hyperactivity impairs cardiogenesis in Down syndrome via downregulation of canonical Wnt signaling

REVISTA / JOURNAL:    - iScience. 2023 Jun 5;26(7):107012. doi: 10.1016/j.isci.2023.107012. eCollection 2023 Jul 21.

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AUTORES / AUTHORS: - Congwu Chi et al

INSTITUCIÓN / INSTITUTION: - Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus; Aurora, CO 80045, USA. 

RESUMEN / SUMMARY: - Congenital heart defects (CHDs) are frequent in children with Down syndrome (DS), caused by trisomy of chromosome 21. However, the underlying mechanisms are poorly understood. Here, using a human-induced pluripotent stem cell (iPSC)-based model and the Dp(16)1Yey/+ (Dp16) mouse model of DS, we identified downregulation of canonical Wnt signaling downstream of increased dosage of interferon (IFN) receptors (IFNRs) genes on chromosome 21 as a causative factor of cardiogenic dysregulation in DS. We differentiated human iPSCs derived from individuals with DS and CHDs, and healthy euploid controls into cardiac cells. We observed that T21 upregulates IFN signaling, downregulates the canonical WNT pathway, and impairs cardiac differentiation. Furthermore, genetic and pharmacological normalization of IFN signaling restored canonical WNT signaling and rescued defects in cardiogenesis in DS in vitro and in vivo. Our findings provide insights into mechanisms underlying abnormal cardiogenesis in DS, ultimately aiding the development of therapeutic strategies.

TÍTULO / TITLE:   - Multidimensional definition of the interferonopathy of Down syndrome and its response to JAK inhibition

REVISTA / JOURNAL:    - Sci Adv. 2023 Jun 28;9(26):eadg6218. doi: 10.1126/sciadv.adg6218. Epub 2023 Jun 28. Free PMC art

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AUTORES / AUTHORS: - Matthew D Galbraith et al

INSTITUCIÓN / INSTITUTION: - Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) display chronic hyperactivation of interferon signaling. However, the clinical impacts of interferon hyperactivity in DS are ill-defined. Here, we describe a multiomics investigation of interferon signaling in hundreds of individuals with DS. Using interferon scores derived from the whole blood transcriptome, we defined the proteomic, immune, metabolic, and clinical features associated with interferon hyperactivity in DS. Interferon hyperactivity associates with a distinct proinflammatory phenotype and dysregulation of major growth signaling and morphogenic pathways. Individuals with the highest interferon activity display the strongest remodeling of the peripheral immune system, including increased cytotoxic T cells, B cell depletion, and monocyte activation. Interferon hyperactivity accompanies key metabolic changes, most prominently dysregulated tryptophan catabolism. High interferon signaling stratifies a subpopulation with elevated rates of congenital heart disease and autoimmunity. Last, a longitudinal case study demonstrated that JAK inhibition normalizes interferon signatures with therapeutic benefit in DS. Together, these results justify the testing of immune-modulatory therapies in DS.

TÍTULO / TITLE:   - Cytogenetic study of subtypes of Down syndrome and its relation with pattern of congenital cardiac defects

REVISTA / JOURNAL:    - J Pak Med Assoc. 2023 Feb;73(2):270-274. doi: 10.47391/JPMA.5422.

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AUTORES / AUTHORS: - Areiba Haider et al

INSTITUCIÓN / INSTITUTION: - Department of Anatomy, King Edward Medical University, Lahore, Pakistan. 

RESUMEN / SUMMARY: - Objective: To determine the frequency of subtypes of Down syndrome by karyotyping, and to establish the frequency of congenital cardiac defects in this population. Methods: The cross-sectional study was conducted at the Department of Genetics, Children Hospital, Lahore, Pakistan, from June 2016 to June 2017, and comprised of Down Syndrome patients aged <15 years. They were subjected to karyotypic analysis for determining the subtype of the syndrome, and echocardiography of all cases was done for the assessment of congenital cardiac defects. The two findings was subsequently used to establish a relation between the subtypes and congenital cardiac defects. Data collected, entered and analyzed by the SPSS version 20.0. Results: Among the 160 cases, trisomy 21 was found in 154(96.2%), translocation 5(3.1%) and mosaicism 1(0.6%). Overall, 63(39.4%) children had cardiac defects. Among such patients, patent ductus arteriosus was most common 25(39.7%), followed by ventricular septal defects24(38.1%), atrial septal defects16(25.4%), complete atrioventricular septal defects 8(12.7%), and Tetralogy of Fallot3(4.8%), while 6(9.5%) children had other defects. Atrial septal defects was the most common double defect 9(56.2%) and had the highest coexistence with patent ductus arteriosus in Down syndrome cases with congenital cardiac defects. Conclusions: In Trisomy 21, the most common cardiac defect was patent ductus arteriosus, followed by ventricular septal defects in isolated defects, whereas in mixed defects, atrial septal defects and patent ductus arteriosus were the highest.

TÍTULO / TITLE:   - Dissection of a Down syndrome-associated trisomy to separate the gene dosage-dependent and -independent effects of an extra chromosome

REVISTA / JOURNAL:    - Hum Mol Genet. 2023 Jun 19;32(13):2205-2218. doi: 10.1093/hmg/ddad056.

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AUTORES / AUTHORS: - Zhuo Xing et al.

INSTITUCIÓN / INSTITUTION: - The Childrens Guild Foundation Down Syndrome Research Program, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. 

RESUMEN / SUMMARY: - As an aneuploidy, trisomy is associated with mammalian embryonic and postnatal abnormalities. Understanding the underlying mechanisms involved in mutant phenotypes is broadly important and may lead to new strategies to treat clinical manifestations in individuals with trisomies, such as trisomy 21 [Down syndrome (DS)]. Although increased gene dosage effects because of a trisomy may account for the mutant phenotypes, there is also the possibility that phenotypic consequences of a trisomy can arise because of the presence of a freely segregating extra chromosome with its own centromere, i.e. a free trisomy independent of gene dosage effects. Presently, there are no reports of attempts to functionally separate these two types of effects in mammals. To fill this gap, here we describe a strategy that employed two new mouse models of DS, Ts65Dn;Df(17)2Yey/+ and Dp(16)1Yey/Df(16)8Yey. Both models carry triplications of the same 103 human chromosome 21 gene orthologs; however, only Ts65Dn;Df(17)2Yey/+ mice carry a free trisomy. Comparison of these models revealed the gene dosage-independent impacts of an extra chromosome at the phenotypic and molecular levels for the first time. They are reflected by impairments of Ts65Dn;Df(17)2Yey/+ males in T-maze tests when compared with Dp(16)1Yey/Df(16)8Yey males. Results from the transcriptomic analysis suggest the extra chromosome plays a major role in trisomy-associated expression alterations of disomic genes beyond gene dosage effects. This model system can now be used to deepen our mechanistic understanding of this common human aneuploidy and obtain new insights into the effects of free trisomies in other human diseases such as cancers.

TÍTULO / TITLE:   - Overexpression screen of chromosome 21 genes reveals modulators of Sonic hedgehog signaling relevant to Down syndrome

REVISTA / JOURNAL:    - Dis Model Mech. 2023 Apr 1;16(4):dmm049712. doi: 10.1242/dmm.049712. Epub 2023 Apr 13. Free PMC art

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AUTORES / AUTHORS: - Anna J Moyer et al.

INSTITUCIÓN / INSTITUTION: - Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 

RESUMEN / SUMMARY: - Trisomy 21 and mutations in the Sonic hedgehog (SHH) signaling pathway cause overlapping and pleiotropic phenotypes including cerebellar hypoplasia, craniofacial abnormalities, congenital heart defects and Hirschsprung disease. Trisomic cells derived from individuals with Down syndrome possess deficits in SHH signaling, suggesting that overexpression of human chromosome 21 genes may contribute to SHH-associated phenotypes by disrupting normal SHH signaling during development. However, chromosome 21 does not encode any known components of the canonical SHH pathway. Here, we sought to identify chromosome 21 genes that modulate SHH signaling by overexpressing 163 chromosome 21 cDNAs in a series of SHH-responsive mouse cell lines. We confirmed overexpression of trisomic candidate genes using RNA sequencing in the cerebella of Ts65Dn and TcMAC21 mice, model systems for Down syndrome. Our findings indicate that some human chromosome 21 genes, including DYRK1A, upregulate SHH signaling, whereas others, such as HMGN1, inhibit SHH signaling. Individual overexpression of four genes (B3GALT5, ETS2, HMGN1 and MIS18A) inhibits the SHH-dependent proliferation of primary granule cell precursors. Our study prioritizes dosage-sensitive chromosome 21 genes for future mechanistic studies. Identification of the genes that modulate SHH signaling may suggest new therapeutic avenues for ameliorating Down syndrome phenotypes.

TÍTULO / TITLE:   - Genetic dissection of triplicated chromosome 21 orthologs yields varying skeletal traits in Down syndrome model mice

REVISTA / JOURNAL:    - Dis Model Mech. 2023 Apr 1;16(4):dmm049927. doi: 10.1242/dmm.049927. Epub 2023 Apr 26

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AUTORES / AUTHORS: - Kourtney Sloan et al

INSTITUCIÓN / INSTITUTION: - 1Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA. 

RESUMEN / SUMMARY: - Down syndrome (DS) phenotypes result from triplicated genes, but the effects of three copy genes are not well known. A mouse mapping panel genetically dissecting human chromosome 21 (Hsa21) syntenic regions was used to investigate the contributions and interactions of triplicated Hsa21 orthologous genes on mouse chromosome 16 (Mmu16) on skeletal phenotypes. Skeletal structure and mechanical properties were assessed in femurs of male and female Dp9Tyb, Dp2Tyb, Dp3Tyb, Dp4Tyb, Dp5Tyb, Dp6Tyb, Ts1Rhr and Dp1Tyb;Dyrk1a+/+/- mice. Dp1Tyb mice, with the entire Hsa21 homologous region of Mmu16 triplicated, display bone deficits similar to those of humans with DS and served as a baseline for other strains in the panel. Bone phenotypes varied based on triplicated gene content, sex and bone compartment. Three copies of Dyrk1a played a sex-specific, essential role in trabecular deficits and may interact with other genes to influence cortical deficits related to DS. Triplicated genes in Dp9Tyb and Dp2Tyb mice improved some skeletal parameters. As triplicated genes can both improve and worsen bone deficits, it is important to understand the interaction between and molecular mechanisms of skeletal alterations affected by these genes.

TÍTULO / TITLE:   - Single-nucleus profiling identifies accelerated oligodendrocyte precursor cell senescence in a mouse model of Down Syndrome

REVISTA / JOURNAL:    - eNeuro. 2023 Jul 24;ENEURO.0147-23.2023. doi: 10.1523/ENEURO.0147-23.2023. Online ahead of print.

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AUTORES / AUTHORS: - Bianca Rusu et al

INSTITUCIÓN / INSTITUTION: - Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1A8, Canada 

RESUMEN / SUMMARY: - Down Syndrome (DS), the most common genetic cause of intellectual disability, is associated with lifelong cognitive deficits. However, the mechanisms by which triplication of chromosome 21 genes drive neuroinflammation and cognitive dysfunction are poorly understood. Here, using the Ts65Dn mouse model of DS, we performed an integrated single-nucleus ATAC and RNA-sequencing (snATAC-seq and snRNA-seq) analysis of the adult cortex. We identified cell type-specific transcriptional and chromatin-associated changes in the Ts65Dn cortex, including regulators of neuroinflammation, transcription and translation, myelination, and mitochondrial function. We discovered enrichment of a senescence-associated transcriptional signature in Ts65Dn oligodendrocyte precursor cells (OPCs) and epigenetic changes consistent with a loss of heterochromatin. We found that senescence is restricted to a subset of OPCs concentrated in deep cortical layers. Treatment of Ts65Dn mice with a senescence-reducing flavonoid rescued cortical OPC proliferation, restored microglial homeostasis, and improved contextual fear memory. Together, these findings suggest that cortical OPC senescence may be an important driver of neuropathology in DS. SIGNIFICANCE STATEMENT Down Syndrome (DS) is the most common genetic cause of intellectual disability worldwide, is characterized by chronic neuroinflammation, and results in a ubiquitous incidence of early-onset neurodegeneration. Here, we conduct single-nucleus multi-omic profiling of the mature adult cortex of an established mouse model of DS, and systematically identify key perturbations in pathways critical for neurogenesis, myelination, and neuroinflammation. We discover the enrichment of a senescence- associated gene signature in trisomic cortical oligodendrocyte precursor cells (OPCs), validate our computational findings using orthogonal approaches, and show that a senescence-reducing flavonoid significantly improves memory deficits. Our findings suggest tha

TÍTULO / TITLE:   - Mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line

REVISTA / JOURNAL:    - Taiwan J Obstet Gynecol. 2023 Jan;62(1):132-136. doi: 10.1016/j.tjog.2022.01.011.

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AUTORES / AUTHORS: - Chih-Ping Chen et al

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan 

RESUMEN / SUMMARY: - Objective: We present mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line. Case report: A 33-year-old woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety, and the karyotype of cultured amniocytes was 47,XX,+21[4]/46,XX[13]. In 17 colonies of cultured amniocytes, four colonies had 47,XX,+21, while the other 13 colonies had 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.32] consistent with 32% mosaicism for trisomy 21. Repeat amniocentesis performed at 25 weeks of gestation revealed 47,XX,+21[4]/46,XX[24] with four colonies of 47,XX,+21 and 24 colonies of 46, XX on cultured amniocytes, and arr 21q11.2q22.3 × 2.25 by aCGH, 19.2% mosaicism for trisomy 21 (20/104 cells) by interphase fluorescence in situ hybridization (FISH), and no uniparental disomy (UPD) 21 by quantitative fluorescence polymerase chain reaction (QF-PCR) on uncultured amniocytes. The parental karyotypes were normal, and prenatal ultrasound was unremarkable. A phenotypically normal 2815-g female baby was delivered at 38 weeks of gestation. Cytogenetic analysis on the cord blood, umbilical cord and placenta revealed the karyotype of 47,XX,+21[10]/46,XX[30]. 47,XX,+21[5]/46,XX[35] and 47,XX,+21[38]/46,XX[2], respectively. QF-PCR analysis on the DNA extracted from parental bloods, uncultured amniocytes, cord blood, umbilical cord and placenta confirmed a paternal origin of trisomy 21. When follow-up at age two months, the neonate was phenotypically normal, the peripheral blood had a karyotype of 47,XX,+21[6]/46,XX[34], and no trisomy 21 signals by interphase FISH was found on 100 buccal mucosal cells. When follow-up at age 13 months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+21[3]/46,XX[37]. Conclusion: Mosaic trisomy 21 at amniocentesis can be a tran

Growth/Development - Crecimiento/Desarrollo

TÍTULO / TITLE:   - Sella Turcica Morphometrics in Subjects with Down Syndrome

REVISTA / JOURNAL:    - J Stomatol Oral Maxillofac Surg. 2023 Jul 11;101559. doi: 10.1016/j.jormas.2023.101559. Online ahea

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AUTORES / AUTHORS: - Petros Papaefthymiou, Elvan Onem Ozbilen

INSTITUCIÓN / INSTITUTION: - School of Dentistry, Department of Orthodontics, Marmara University, Istanbul, Turkey. 

RESUMEN / SUMMARY: - Objective: Since the number of patients diagnosed with Down syndrome seeking orthodontic treatment is increasing, clinicians could contribute by applying diagnostic modalities used frequently in the orthodontic field for research purposes. Thus, The aim of the present study is to implement morphometric methods to investigate the size and shape of sella turcica in subjects with Down syndrome. Materials and methods: In this retrospective study, archive records of 24 individuals with Down syndrome were compared to 48 healthy controls matched for age and gender. Parameters such as sella anterior, midpoint, and posterior height were measured, as well as sella width, area, and length were calculated. Independent sample t-tests were applied for the comparison of differences in sella turcica dimensions. Geometric morphometric analysis of the sella was performed with, implementing methods such as Procrustes superimposition and principal component analysis. Statistical significance was set at p<0.05. Results: Statistically significant differences were found for sella anterior height, sella midpoint height, sella posterior height, sella maximum height, sella length, and sella area. All the aforementioned values were significantly increased in the Down syndrome subjects (p<0.05). Principal component analysis (PCA) depicted a statistically significant difference in sella shape between patients with Down syndrome and healthy controls (p<0.05). Conclusions: Subjects with Down syndrome presented significantly increased sella turcica dimensions as well statistically significant differences in shape compared to healthy controls.

Gynecology - Ginecología

TÍTULO / TITLE:   - Concerns Regarding Gynecological Aspects of Brazilian Girls and Women With Down Syndrome: A Cross-Sectional Study of Caregivers Opinions

REVISTA / JOURNAL:    - Ann Fam Med. 2023 Jul-Aug;21(4):322-326. doi: 10.1370/afm.2993.

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AUTORES / AUTHORS: - Gustavo Wandresen et al

INSTITUCIÓN / INSTITUTION: - Post Graduate Program in Gynecology and Obstetrics, Federal University of Paraná, Curitiba, Brazil. 

RESUMEN / SUMMARY: - Purpose: Girls and women with Down syndrome (DS) and their caregivers may have more difficulties in dealing with puberty, menstruation, and sexuality than those without DS. Our aim was to understand the concerns of these caregivers about gynecological aspects, including menstruation, contraception, and sexual practice. Methods: We performed a cross-sectional study that included caregivers of females with DS aged 9 years or older and both in pre- and post-menarche. The caregivers answered a questionnaire about their concerns regarding puberty, menstruation, sexuality, and contraception methods. Results: We enrolled 100 caregivers of females with DS. Caregivers major concern was menstrual bleeding. Most caregivers (57%) would not prohibit romantic relationships, including sexual relationships. Of the care recipients, 78 had reached menarche and their most common complaints were pain and behavioral changes. Regarding sexual behavior, 2% had already had sexual intercourse. Contraception was used by 14 of the 78 (17.9%) post-menarche females with weight gain as the most common side effect (43%). Conclusions: In our sample, females with DS had sexual development comparable to those without the syndrome. As these females become increasingly independent, it is necessary to guide caregivers and primary care physicians, especially gynecologists, about the difficulties related to the menstrual period.

TÍTULO / TITLE:   - DNA methylation profiling in Trisomy 21 females with and without breast cancer

REVISTA / JOURNAL:    - Front Oncol. 2023 Jul 19;13:1203483. doi: 10.3389/fonc.2023.1203483. eCollection 2023

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AUTORES / AUTHORS: - Yosra Bejaoui et al

INSTITUCIÓN / INSTITUTION: - College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar 

RESUMEN / SUMMARY: - Background: Down Syndrome (DS) is the most common chromosome anomaly in humans and occurs due to an extra copy of chromosome 21. The malignancy profile in DS is unique, since DS patients have a low risk of developing solid tumors such as breast cancer however they are at higher risk of developing acute myeloid leukemia and acute lymphoblastic leukemia. Methods: In this study, we investigated DNA methylation signatures and epigenetic aging in DS individuals with and without breast cancer. We analyzed DNA methylation patterns in Trisomy 21 (T21) individuals without breast cancer (T21-BCF) and DS individuals with breast cancer (T21-BC), using the Infinium Methylation EPIC BeadChip array. Results: Our results revealed several differentially methylated sites and regions in the T21-BC patients that were associated with changes in gene expression. The differentially methylated CpG sites were enriched for processes related to serine-type peptidase activity, epithelial cell development, GTPase activity, bicellular tight junction, Ras protein signal transduction, etc. On the other hand, the epigenetic age acceleration analysis showed no difference between T21-BC and T21-BCF patients. Conclusions: This is the first study to investigate DNA methylation changes in Down syndrome women with and without breast cancer and it could help shed light on factors that protect against breast cancer in DS.

TÍTULO / TITLE:   - Levonorgestrel-Releasing Intrauterine System Utilization in Patients with Developmental Delays

REVISTA / JOURNAL:    - J Pediatr Adolesc Gynecol. 2023 Feb;36(1):79-82. doi: 10.1016/j.jpag.2022.09.003. Epub 2022 Sep 8

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AUTORES / AUTHORS: - C M Lutz et al

INSTITUCIÓN / INSTITUTION: - Center for Surgical Outcomes, The Abigail Wexner Research Institute at Nationwide Childrens Hospital, Columbus, Ohio. 

RESUMEN / SUMMARY: - Introduction: Adolescent females with developmental delays (DDs) experience unique physical and emotional challenges related to menstruation. Providers often recommend hormonal medication for menstrual management. The objective of our study was to describe the utilization and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) in adolescents with DDs. Methods: We utilized the Pediatric Health Information System to identify females aged 10-25 with DDs who underwent an LNG-IUS insertion between 2011 and 2020. Using a gynecologic procedure and diagnosis codes, we assessed indications for and complications of LNG-IUS use. We also evaluated early LNG-IUS removal. Results: One thousand five hundred and sixty female patients with DDs underwent LNG-IUS insertion. LNG-IUS insertion under anesthesia was most commonly performed in patients with autism and Down syndrome, and unspecified menstrual issues were documented for 40% of the cohort. Perforation was observed in 11 patients (1%), and mechanical complications (malpositioned IUS or lost threads) were observed in 23 patients (1%). Discussion: This is the largest analysis of LNG-IUS use in patients with DDs to our knowledge and shows the utilization of LNG-IUS in patients with DDs. We provide descriptive information that providers can use to accurately advise their patients with DDs on the risks and benefits of LNG-IUS use for menstrual management.

Hematology/Oncology - Hematología/Oncología

TÍTULO / TITLE:   - Genomic landscape of Down syndrome-associated acute lymphoblastic leukemia

REVISTA / JOURNAL:    - Blood. 2023 Jul 13;142(2):172-184. doi: 10.1182/blood.2023019765.

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AUTORES / AUTHORS: - Zhenhua Li et al

INSTITUCIÓN / INSTITUTION: - Department of Pharmacy and Pharmaceutical Sciences, St. Jude Childrens Research Hospital, Memphis, TN. 

RESUMEN / SUMMARY: - Trisomy 21, the genetic cause of Down syndrome (DS), is the most common congenital chromosomal anomaly. It is associated with a 20-fold increased risk of acute lymphoblastic leukemia (ALL) during childhood and results in distinctive leukemia biology. To comprehensively define the genomic landscape of DS-ALL, we performed whole-genome sequencing and whole-transcriptome sequencing (RNA-Seq) on 295 cases. Our integrated genomic analyses identified 15 molecular subtypes of DS-ALL, with marked enrichment of CRLF2-r, IGH::IGF2BP1, and C/EBP altered (C/EBPalt) subtypes compared with 2257 non-DS-ALL cases. We observed abnormal activation of the CEBPD, CEBPA, and CEBPE genes in 10.5% of DS-ALL cases via a variety of genomic mechanisms, including chromosomal rearrangements and noncoding mutations leading to enhancer hijacking. A total of 42.3% of C/EBP-activated DS-ALL also have concomitant FLT3 point mutations or insertions/deletions, compared with 4.1% in other subtypes. CEBPD overexpression enhanced the differentiation of mouse hematopoietic progenitor cells into pro-B cells in vitro, particularly in a DS genetic background. Notably, recombination-activating gene-mediated somatic genomic abnormalities were common in DS-ALL, accounting for a median of 27.5% of structural alterations, compared with 7.7% in non-DS-ALL. Unsupervised hierarchical clustering analyses of CRLF2-rearranged DS-ALL identified substantial heterogeneity within this group, with the BCR::ABL1-like subset linked to an inferior event-free survival, even after adjusting for known clinical risk factors. These results provide important insights into the biology of DS-ALL and point to opportunities for targeted therapy and treatment individualization.

TÍTULO / TITLE:   - All about Down syndrome ALL

REVISTA / JOURNAL:    - Blood. 2023 Jul 13;142(2):126-128. doi: 10.1182/blood.2023020508

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AUTORES / AUTHORS: - Zhaohui Gu, Shai Izraeli

INSTITUCIÓN / INSTITUTION: - Beckman Research Institute of City of Hope 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Myeloid Leukemia of Down Syndrome

REVISTA / JOURNAL:    - Cancers (Basel). 2023 Jun 21;15(13):3265. doi: 10.3390/cancers15133265. Free PMC article

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AUTORES / AUTHORS: - Aikaterini Kosmidou et al

INSTITUCIÓN / INSTITUTION: - 2nd Department of Internal Medicine, General Hospital of Kavala, 65500 Kavala, Greece 

RESUMEN / SUMMARY: - Myeloid leukemia of Down syndrome (ML-DS) is characterized by a distinct natural history and is classified by the World Health Organization (WHO) as an independent entity, occurring with unique clinical and molecular features. The presence of a long preleukemic, myelodysplastic phase, called transient abnormal myelopoiesis (TAM), precedes the initiation of ML-DS and is defined by unusual chromosomal findings. Individuals with constitutional trisomy 21 have a profound dosage imbalance in the hematopoiesis-governing genes located on chromosome 21 and thus are subject to impaired fetal as well as to neonatal erythro-megakaryopoiesis. Almost all neonates with DS develop quantitative and morphological hematological abnormalities, yet still only 5-10% of them present with one of the preleukemic or leukemic conditions of DS. The acquired mutations in the key hematopoietic transcription factor gene GATA1, found solely in cells trisomic for chromosome 21, are considered to be the essential step for the selective growth advantage of leukemic cells. While the majority of cases of TAM remain clinically silent or undergo spontaneous remission, the remaining 20% to 30% of them progress into ML-DS until the age of 4 years. The hypersensitivity of ML-DS blasts to chemotherapeutic agents, including but not limited to cytarabine, and drugs increased infectious and cardiac toxicity have necessitated the development of risk-adapted treatment protocols for children with ML-DS. Recent advances in cytogenetics and specific molecular mechanisms involved in the evolution of TAM and ML-DS are reviewed here, as well as their integration in the improvement of risk stratification and targeted management of ML-DS.

TÍTULO / TITLE:   - Down syndrome and leukemia: from basic mechanisms to clinical advances

REVISTA / JOURNAL:    - Haematologica. 2023 Jul 13. doi: 10.3324/haematol.2023.283225. Online ahead of print. Free artic

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AUTORES / AUTHORS: - Andre Baruchel et al

INSTITUCIÓN / INSTITUTION: - Hopital Universitaire Robert Debre (APHP and Universite Paris Cite), Paris 

RESUMEN / SUMMARY: - Children with Down syndrome (DS, trisomy 21) are at a significantly higher risk of developing acute leukemia compared to the overall population. Many studies investigating the link between trisomy 21 (T21) and leukemia initiation and progression have been conducted over the last two decades. Despite improved treatment regimens and significant progress in identifying genes on chromosome 21 and the mechanisms by which they drive leukemogenesis, there is still much that is unknown. A focused group of scientists and clinicians with expertise in leukemia and Down syndrome met in October 2022 at the Jérôme Lejeune Foundation in Paris, France for the 1st International Symposium on Down Syndrome and Leukemia. This meeting was held to discuss the most recent advances in treatment regimens and the biology underlying the initiation, progression, and relapse of acute lymphoblastic leukemia and acute myeloid leukemia in children with DS. This review provides a summary of what is known in the field, challenges in the management of DS patients with leukemia, and key questions in the field.

TÍTULO / TITLE:   - Acute basophilic leukemia in a patient with down syndrome: A case report and review of literature

REVISTA / JOURNAL:    - Int J Lab Hematol. 2023 Jun 19. doi: 10.1111/ijlh.14117. Online ahead of print.

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AUTORES / AUTHORS: - Anu Singh et al.

INSTITUCIÓN / INSTITUTION: - Hematopathology Laboratory, ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Navi Mumbai, India 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Common Blood Test Indices for Predicting Transient Abnormal Myelopoiesis-Related Mortality in Infants with Down Syndrome

REVISTA / JOURNAL:    - Tohoku J Exp Med. 2023 Jun 22. doi: 10.1620/tjem.2023.J051. Online ahead of print

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AUTORES / AUTHORS: - Hideyuki Hawaka et al

INSTITUCIÓN / INSTITUTION: - Department of Neonatology, Kanagawa Childrens Medical Center 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Downregulation of the long noncoding RNA DSCR9 (Down syndrome critical region 9) delays breast cancer progression by modulating microRNA-504-5p-dependent G protein-coupled receptor 65

REVISTA / JOURNAL:    - Hum Cell. 2023 Jul;36(4):1516-1534. doi: 10.1007/s13577-023-00916-4. Epub 2023 May 29

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AUTORES / AUTHORS: - Mingzhu Li et al

INSTITUCIÓN / INSTITUTION: - Area N4 of Surgical Oncology, Quanzhou First Hospital Affiliated Fujian Medical University, No. 1028, Anji South Road, Fengze District, Quanzhou, 362000, Fujian Province, China.  

RESUMEN / SUMMARY: - Possible roles of long noncoding RNAs (lncRNAs) in cancer stem cells (CSCs) have often been reported. Here, we focused on the regulatory function of the lncRNA Down syndrome critical region 9 (DSCR9) in breast cancer stem cells (BCSCs). Through bioinformatics analysis, DSCR9, microRNA-504-5p (miR-504-5p), and G protein-coupled receptor 65 (GPR65) were identified as targets implicated in breast cancer development. Then, clinical tissue samples, breast cancer cells, and isolated BCSCs were used to determine the expression of DSCR9, miR-504-5p, and GPR65. The results confirmed the overexpression of DSCR9 and GPR65 but low expression of miR-504-5p in breast cancer tissues and cells as well as in BCSCs. Following mechanistic investigation, it was found that DSCR9 targeted miR-504-5p, and that silencing DSCR9 inhibited the proliferation of BCSCs by elevating the expression of miR-504-5p. Additionally, miR-504-5p targeted GPR65 and inhibited its expression. Moreover, GPR65 activated the MEK/ERK signaling pathway to regulate BCSC proliferation. Finally, animal study verified that depletion of DSCR9 inhibited the proliferation of BCSCs in vivo and that BCSC proliferation was restored by overexpression of GPR65. Altogether, our findings revealed that DSCR9 elevated GPR65 expression by targeting miR-504-5p to exacerbate breast cancer, highlighting a new treatment modality for breast cancer.

TÍTULO / TITLE:   - Management of Down Syndrome-Associated Leukemias: A Review

REVISTA / JOURNAL:    - JAMA Oncol. 2023 Jul 13. doi: 10.1001/jamaoncol.2023.2163. Online ahead of print.

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AUTORES / AUTHORS: - Anupam Verma et al

INSTITUCIÓN / INSTITUTION: - Pediatric Oncology Branch, Center for Cancer Research (CCR), NCI, NIH, Bethesda, Maryland 

RESUMEN / SUMMARY: - Importance: Down syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recognized for decades, consisting of an approximately 150-fold higher risk of acute myeloid leukemia (AML) before age 4 years, and a 10- to 20-fold higher risk of acute lymphoblastic leukemia (ALL), compared with children without DS. Observations: A recent National Institutes of Health-sponsored conference, ImpacT21, reviewed research and clinical trials in children, adolescents, and young adults (AYAs) with DS-AL and are presented herein, including presentation and treatment, clinical trial design, and ethical considerations for this unique population. Between 10% to 30% of infants with DS are diagnosed with transient abnormal myelopoiesis (TAM), which spontaneously regresses. After a latency period of up to 4 years, 20% to 30% develop myeloid leukemia associated with DS (ML-DS). Recent studies have characterized somatic mutations associated with progression from TAM to ML-DS, but predicting which patients will progress to ML-DS remains elusive. Clinical trials for DS-AL have aimed to reduce treatment-related mortality (TRM) and improve survival. Children with ML-DS have better outcomes compared with non-DS AML, but outcomes remain dismal in relapse. In contrast, patients with DS-ALL have inferior outcomes compared with those without DS, due to both higher TRM and relapse. Management of relapsed leukemia poses unique challenges owing to disease biology and increased vulnerability to toxic effects. Late effects in survivors of DS-AL are an important area in need of further study because they may demonstrate unique patterns in the setting of chronic medical conditions associated with DS. Conclusions and relevance: Optimal management of DS-AL requires specific molecular testing, meticulous supportive care, and tailored therapy to reduce TRM while optimizing survival. There is

TÍTULO / TITLE:   - Importance: Down syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recogn

REVISTA / JOURNAL:    - J Cell Mol Med. 2023 Aug;27(15):2228-2238. doi: 10.1111/jcmm.17817. Epub 2023 Jul 6. Free PMC artic

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AUTORES / AUTHORS: - Guillaume Postic et al

INSTITUCIÓN / INSTITUTION: - Université Paris Cité, BFA, UMR 8251, CNRS, ERLU1133, Paris, France 

RESUMEN / SUMMARY: - Down syndrome is the most common chromosomal abnormality in humans. Patients with Down syndrome have hematologic disorders, including mild to moderate thrombocytopenia. In case of Down syndrome, thrombocytopenia is not associated with bleeding, and it remains poorly characterized regarding molecular mechanisms. We investigated the effects of overexpression of Dyrk1A, an important factor contributing to some major Down syndrome phenotypes, on platelet number and bleeding in mice. Mice overexpressing Dyrk1A have a decrease in platelet number by 20%. However, bleeding time was found to be reduced by 50%. The thrombocytopenia and the decreased bleeding time observed were not associated to an abnormal platelet receptors expression, to a defect of platelet activation by ADP, thrombin or convulxin, to the presence of activated platelets in the circulation or to an abnormal half-life of the platelets. To propose molecular mechanisms explaining this discrepancy, we performed a network analysis of Dyrk1A interactome and demonstrated that Dyrk1A, fibronectin and fibrinogen interact indirectly through two distinct clusters of proteins. Moreover, in mice overexpressing Dyrk1A, increased plasma fibronectin and fibrinogen levels were found, linked to an increase of the hepatic fibrinogen production. Our results indicate that overexpression of Dyrk1A in mice induces decreased bleeding consistent with increased plasma fibronectin and fibrinogen levels, revealing a new role of Dyrk1A depending on its indirect interaction with these two proteins.

TÍTULO / TITLE:   - DNA methylation profiling in Trisomy 21 females with and without breast cancer

REVISTA / JOURNAL:    - Front Oncol. 2023 Jul 19;13:1203483. doi: 10.3389/fonc.2023.1203483. eCollection 2023

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AUTORES / AUTHORS: - Yosra Bejaoui et al

INSTITUCIÓN / INSTITUTION: - College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar 

RESUMEN / SUMMARY: - Background: Down Syndrome (DS) is the most common chromosome anomaly in humans and occurs due to an extra copy of chromosome 21. The malignancy profile in DS is unique, since DS patients have a low risk of developing solid tumors such as breast cancer however they are at higher risk of developing acute myeloid leukemia and acute lymphoblastic leukemia. Methods: In this study, we investigated DNA methylation signatures and epigenetic aging in DS individuals with and without breast cancer. We analyzed DNA methylation patterns in Trisomy 21 (T21) individuals without breast cancer (T21-BCF) and DS individuals with breast cancer (T21-BC), using the Infinium Methylation EPIC BeadChip array. Results: Our results revealed several differentially methylated sites and regions in the T21-BC patients that were associated with changes in gene expression. The differentially methylated CpG sites were enriched for processes related to serine-type peptidase activity, epithelial cell development, GTPase activity, bicellular tight junction, Ras protein signal transduction, etc. On the other hand, the epigenetic age acceleration analysis showed no difference between T21-BC and T21-BCF patients. Conclusions: This is the first study to investigate DNA methylation changes in Down syndrome women with and without breast cancer and it could help shed light on factors that protect against breast cancer in DS.

Infectious diseases - Infecciones

TÍTULO / TITLE:   - Multidimensional definition of the interferonopathy of Down syndrome and its response to JAK inhibition

REVISTA / JOURNAL:    - Sci Adv. 2023 Jun 28;9(26):eadg6218. doi: 10.1126/sciadv.adg6218. Epub 2023 Jun 28.

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AUTORES / AUTHORS: - Matthew D Galbraith et al

INSTITUCIÓN / INSTITUTION: - Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) display chronic hyperactivation of interferon signaling. However, the clinical impacts of interferon hyperactivity in DS are ill-defined. Here, we describe a multiomics investigation of interferon signaling in hundreds of individuals with DS. Using interferon scores derived from the whole blood transcriptome, we defined the proteomic, immune, metabolic, and clinical features associated with interferon hyperactivity in DS. Interferon hyperactivity associates with a distinct proinflammatory phenotype and dysregulation of major growth signaling and morphogenic pathways. Individuals with the highest interferon activity display the strongest remodeling of the peripheral immune system, including increased cytotoxic T cells, B cell depletion, and monocyte activation. Interferon hyperactivity accompanies key metabolic changes, most prominently dysregulated tryptophan catabolism. High interferon signaling stratifies a subpopulation with elevated rates of congenital heart disease and autoimmunity. Last, a longitudinal case study demonstrated that JAK inhibition normalizes interferon signatures with therapeutic benefit in DS. Together, these results justify the testing of immune-modulatory therapies in DS.

TÍTULO / TITLE:   - Down Syndrome Outreach During the COVID-19 Pandemic: An Interprofessional Zoom WhatsApp Collaboration in Syria

REVISTA / JOURNAL:    - J Pediatr Health Care. 2023 Mar-Apr;37(2):103-105. doi: 10.1016/j.pedhc.2022.10.003. Epub 2022 Oct

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AUTORES / AUTHORS: - Margaret H Wolf et al

INSTITUCIÓN / INSTITUTION: - Child Development and Rehabilitation Center, Oregon Health & Science University, Portland, OR. 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - The Impact of COVID-19 Pandemic on Patient Admissions to the Developmental Pediatrics Unit: An Outpatient Clinic in Eastern Turkey

REVISTA / JOURNAL:    - Turk Arch Pediatr. 2023 Jan;58(1):62-67. doi: 10.5152/TurkArchPediatr.2022.22200.

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AUTORES / AUTHORS: - Tugba Karaca Ahat et al

INSTITUCIÓN / INSTITUTION: - Department of Developmental Pediatrics, İnonu University, Medical Faculty, Malatya, Turkey 

RESUMEN / SUMMARY: - Objective: The aim of this study was to analyze the impact of coronavirus disease 2019 pandemic on the number and diagnosis of patients admitted to the Developmental Pediatrics Unit. Materilas and Methods: We compared the number and the diagnosis of patients admitted to the Developmental Pediatrics Unit by using International Classification of Diseases and Related Health Problems 10th revision (ICD-10) codes of our institutions electronic health data before and after 18 months from March 16 2020, when coronavirus disease 2019 pandemic was declared in Turkey. Statistical analyses were performed by using International Business Machines Statistical Package for Social Sciences for windows version 22.0 (Armonk, NY) program. Results: We found that the number of patients admitted to the Developmental Pediatrics Unit decreased during the pandemic period (pre-coronavirus disease 2019 n = 1107, during coronavirus disease 2019 n = 761). There was no significant difference between the ratio of the most common diagnosis (prematurity) before and during the pandemic period (32% and 30.6% respectively). It was observed that the ratio of children with speech delay (17.4%-23%, P = .003) increased during the pandemic, while there was a significant decrease in the ratio of admissions with Down syndrome (11.6%-6.6%, P < .001). Conclusion: We found that the number of admissions to the Developmental Pediatrics Unit with developmental difficulties decreased significantly during the pandemic. The ratio of admissions of speech delay increased during the same period, while admissions with Down syndrome decreased. This increase may be due to lockdown, increase in electronic screen exposure, and lack of stimuli and the decrease may be due to the risk of severe illness from coronavirus disease 2019. The decrease in admissions of patients who require developmental follow-up reveals the need for additional efforts such as implementing tele-health to our daily practice.

TÍTULO / TITLE:   - Healthcare and Behavior Changes for Adults With Down Syndrome 1-Year Into COVID-19

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2023 Jul 1;128(4):273-281. doi: 10.1352/1944-7558-128.4.273

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AUTORES / AUTHORS: - Eric Rubenstein et al.

INSTITUCIÓN / INSTITUTION: - Boston University School of Public Health. 

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) have been disproportionately harmed by the COVID-19 pandemic and may have been more likely to have sacrificed opportunity and activity to avoid potential exposures. Our objective was to describe the experience one to one and half years into the COVID-19 pandemic for adults with DS, as reported by their caregivers in an online survey conducted between April 2021 and September of 2021. In our sample of 438 adults with DS, caregivers reported that adults with DS lost activities, struggled with employment, had negative behavioral changes, lost skills, and developed more mental health conditions. For adults with DS, one in five caregivers reported less healthcare usage, one in four reported delayed routine care, and 86.5% reported lost activities. As the pandemic continues, targeted support for adults with DS is needed to prevent further skill loss and mental health conditions.

TÍTULO / TITLE:   - Disinfection behavior for COVID-19 in individuals with Down syndrome and caregivers distress in Japan: a cross-sectional retrospective study

REVISTA / JOURNAL:    - J Dev Phys Disabil. 2023;35(1):81-96. doi: 10.1007/s10882-022-09845-w. Epub 2022 May 26.

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AUTORES / AUTHORS: - Haruo Fujino, Minori Itai

INSTITUCIÓN / INSTITUTION: - Department of Child Development, Graduate School of Child Development, Osaka University, 2-2 Yamadaoka, 5650871 Suita, Japan 

RESUMEN / SUMMARY: - The COVID-19 outbreak affected the daily lives of individuals with Down syndrome, who were considered to have a higher risk of severe infection. While several studies have reported mental health issues in children and/or parents in the general population, no study has focused on people with Down syndrome and their caregivers. This study investigated the disinfection behaviors of individuals with Down syndrome and their caregivers stress. A cross-sectional retrospective survey was conducted in October 2020. Caregivers of children and adults with Down syndrome were administered questionnaires including measures for practiced disinfection behavior in children, caregivers child-related stress, and psychological distress. About half of the respondents children practiced hand hygiene and mask-wearing behaviors, while physical distancing was performed less frequently. Habitual practices in physical distancing are affected by intellectual function. Logistic regression showed that caregivers stress was associated with the irritability of individuals with the disorder (adjusted odds ratio [OR] = 8.44, 95% confidence interval [CI] 1.69-42.09) and the burden of infection-prevention behaviors for people with Down syndrome (adjusted OR = 4.26, 95% CI 1.88-9.65). This study showed the characteristics of disinfection behaviors in individuals with Down syndrome and associated factors for serious caregiver stress.

TÍTULO / TITLE:   - The impact of COVID-19 (Coronavirus) on children and young people with Down syndrome in the United Kingdom

REVISTA / JOURNAL:    - Front Psychol. 2023 Jun 2;14:1175636. doi: 10.3389/fpsyg.2023.1175636. eCollection 2023.

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AUTORES / AUTHORS: - Emma Pagnamenta et al

INSTITUCIÓN / INSTITUTION: - School of Psychology and Clinical Language Sciences, University of Reading, Reading, United Kingdom 

RESUMEN / SUMMARY: - The COVID-19 pandemic had a profound impact across the globe. Evidence suggests children with Special Educational Needs and Disabilities and their families experienced impacts on well-being and disruptions in support from education and health services. This study investigated the impact of measures associated with the COVID-19 pandemic on children and young people (CYP) with Down syndrome in the United Kingdom, specifically changes in speech, language and communication abilities, behavior, social, emotional and mental health and access to education and healthcare services. Forty-six parents/carers of CYP with Down Syndrome (aged 2-25 years) completed an online survey between June and September 2020. Parents/carers frequently reported deterioration in speech, language and communication, literacy and attention skills since the onset of the pandemic. Deterioration in social and emotional wellbeing and behavior, including greater reliance on adults were also reported for some CYP with Down syndrome. Parents reported challenges with home-schooling and reductions in support from education and community services. Preferences for support during COVID-19 were for professional support or from other parents. These findings have implications for the support that is now needed for CYP with Down syndrome and their families and for periods of social restrictions in the future.

Molecular biology/Biochemistry - Biología molecular/Bioquímica

TÍTULO / TITLE:   - RNA Therapeutics: A Healthcare Paradigm Shift

REVISTA / JOURNAL:    - Biomedicines. 2023 Apr 25;11(5):1275. doi: 10.3390/biomedicines11051275.

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AUTORES / AUTHORS: - Sarfaraz K Niazi

INSTITUCIÓN / INSTITUTION: - College of Pharmacy, University of Illinois, Chicago, IL 60612, USA 

RESUMEN / SUMMARY: - COVID-19 brought about the mRNA vaccine and a paradigm shift to a new mode of treating and preventing diseases. Synthetic RNA products are a low-cost solution based on a novel method of using nucleosides to act as an innate medicine factory with unlimited therapeutic possibilities. In addition to the common perception of vaccines preventing infections, the newer applications of RNA therapies include preventing autoimmune disorders, such as diabetes, Parkinsons disease, Alzheimers disease, and Down syndrome; now, we can deliver monoclonal antibodies, hormones, cytokines, and other complex proteins, reducing the manufacturing hurdles associated with these products. Newer PCR technology removes the need for the bacterial expression of DNA, making mRNA a truly synthetic product. AI-driven product design expands the applications of mRNA technology to repurpose therapeutic proteins and test their safety and efficacy quickly. As the industry focuses on mRNA, many novel opportunities will arise, as hundreds of products under development will bring new perspectives based on this significant paradigm shift-finding newer solutions to existing challenges in healthcare.

TÍTULO / TITLE:   - Mitochondrial Dysfunction in Down Syndrome: From Pathology to Therapy

REVISTA / JOURNAL:    - Neuroscience. 2023 Feb 10;511:1-12. doi: 10.1016/j.neuroscience.2022.12.003. Epub 2022 Dec 7.

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AUTORES / AUTHORS: - Kai-Leng Tan et al

INSTITUCIÓN / INSTITUTION: - Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia; Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Se 

RESUMEN / SUMMARY: - Mitochondrial dysfunctions have been described in Down syndrome (DS) caused by either partial or full trisomy of chromosome 21 (HSA21). Mitochondria play a crucial role in various vital functions in eukaryotic cells, especially in energy production, calcium homeostasis and programmed cell death. The function of mitochondria is primarily regulated by genes encoded in the mitochondrion and nucleus. Many genes on HSA21 are involved in oxidative phosphorylation (OXPHOS) and regulation of mitochondrial functions. This review highlights the HSA21 dosage-sensitive nuclear-encoded mitochondrial genes associated with overexpression-related phenotypes seen in DS. This includes impaired mitochondrial dynamics, structural defects and dysregulated bioenergetic profiles such as OXPHOS deficiency and reduced ATP production. Various therapeutic approaches for modulating energy deficits in DS, effects and molecular mechanism of gene therapy and drugs that exert protective effects through modulation of mitochondrial function and attenuation of oxidative stress in DS cells were discussed. It is prudent that improving DS pathophysiological conditions or quality of life may be feasible by targeting something as simple as cellular mitochondrial biogenesis and function.

TÍTULO / TITLE:   - Therapeutics for mitochondrial dysfunction-linked diseases in Down syndrome

REVISTA / JOURNAL:    - Mitochondrion. 2023 Jan;68:25-43. doi: 10.1016/j.mito.2022.11.003. Epub 2022 Nov 9.

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AUTORES / AUTHORS: - Bani Bandana Ganguly, Nitin N Kadam

INSTITUCIÓN / INSTITUTION: - MGM New Bombay Hospital and MGM Institute of Health Sciences, Navi Mumbai, India. 

RESUMEN / SUMMARY: - Genome-wide deregulation contributes to mitochondrial dysfunction and impairment in oxidative phosphorylation (OXPHOS) mechanism resulting in oxidative stress, increased production of reactive oxygen species (ROS) and cell death in individuals with Down syndrome (DS). The cells, which require more energy, such as muscles, brain and heart are greatly affected. Impairment in mitochondrial network has a direct link with patho-mechanism at cellular and systemic levels at the backdrop of generalized metabolic perturbations in individuals with DS. Myriads of clinico-phenotypic features, including intellectual disability, early aging and neurodegeneration, and Alzheimer disease (AD)-related dementia are inevitable in DS-population where mitochondrial dysfunctions play the central role. Collectively, the mitochondrial abnormalities and altered energy metabolism perturbs several signaling pathways, particularly related to neurogenesis, which are directly associated with cognitive development and early onset of AD in individuals with DS. Therefore, therapeutic challenges for amelioration of the mitochondrial defects were perceived to improve the quality of life of the DS population. A number of pharmacologically active natural compounds such as polyphenols, antioxidants and flavonoids have shown convincing outcome for reversal of the dysfunctional mitochondrial network and oxidative metabolism, and improvement in intellectual skill in mouse models of DS and humans with DS.

TÍTULO / TITLE:   - Single-cell landscape analysis reveals systematic senescence in mammalian Down syndrome

REVISTA / JOURNAL:    - Clin Transl Med. 2023 Jul;13(7):e1310. doi: 10.1002/ctm2.1310.

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AUTORES / AUTHORS: - Yao Chen et al

INSTITUCIÓN / INSTITUTION: - Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Womens Hospital, Zhejiang University School of Medicine, Hangzhou, China. 

RESUMEN / SUMMARY: - Background: Down syndrome (DS), which is characterized by various malfunctions, is the most common chromosomal disorder. As the DS population continues to grow and most of those with DS live beyond puberty, early-onset health problems have become apparent. However, the cellular landscape and molecular alterations have not been thoroughly studied. Methods: This study utilized single-cell resolution techniques to examine DS in humans and mice, spanning seven distinct organs. A total of 71 934 mouse and 98 207 human cells were analyzed to uncover the molecular alterations occurring in different cell types and organs related to DS, specifically starting from the fetal stage. Additionally, SA-β-Gal staining, western blot, and histological study were employed to verify the alterations. Results: In this study, we firstly established the transcriptomic profile of the mammalian DS, deciphering the cellular map and molecular mechanism. Our analysis indicated that DS cells across various types and organs experienced senescence stresses from as early as the fetal stage. This was marked by elevated SA-β-Gal activity, overexpression of cell cycle inhibitors, augmented inflammatory responses, and a loss of cellular identity. Furthermore, we found evidence of mitochondrial disturbance, an increase in ribosomal protein transcription, and heightened apoptosis in fetal DS cells. This investigation also unearthed a regulatory network driven by an HSA21 gene, which leads to genome-wide expression changes. Conclusion: The findings from this study offer significant insights into the molecular alterations that occur in DS, shedding light on the pathological processes underlying this disorder. These results can potentially guide future research and treatment development for DS.

TÍTULO / TITLE:   - REST Targets JAK-STAT and HIF-1 Signaling Pathways in Human Down Syndrome Brain and Neural Cells

REVISTA / JOURNAL:    - Int J Mol Sci. 2023 Jun 10;24(12):9980. doi: 10.3390/ijms24129980

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AUTORES / AUTHORS: - Tan Huang et al

INSTITUCIÓN / INSTITUTION: - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia 

RESUMEN / SUMMARY: - Down syndrome (DS) is the most frequently diagnosed chromosomal disorder of chromosome 21 (HSA21) aneuploidy, characterized by intellectual disability and reduced lifespan. The transcription repressor, Repressor Element-1 Silencing Transcription factor (REST), which acts as an epigenetic regulator, is a crucial regulator of neuronal and glial gene expression. In this study, we identified and investigated the role of REST-target genes in human brain tissues, cerebral organoids, and neural cells in Down syndrome. Gene expression datasets generated from healthy controls and DS samples of human brain tissues, cerebral organoids, NPC, neurons, and astrocytes were retrieved from the Gene Ontology (GEO) and Sequence Read Archive (SRA) databases. Differential expression analysis was performed on all datasets to produce differential expression genes (DEGs) between DS and control groups. REST-targeted DEGs were subjected to functional ontologies, pathways, and network analyses. We found that REST-targeted DEGs in DS were enriched for the JAK-STAT and HIF-1 signaling pathways across multiple distinct brain regions, ages, and neural cell types. We also identified REST-targeted DEGs involved in nervous system development, cell differentiation, fatty acid metabolism and inflammation in the DS brain. Based on the findings, we propose REST as the critical regulator and a promising therapeutic target to modulate homeostatic gene expression in the DS brain.

TÍTULO / TITLE:   - Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome

REVISTA / JOURNAL:    - bioRxiv. 2023 Jul 5;2023.07.05.547813. doi: 10.1101/2023.07.05.547813. Preprint

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AUTORES / AUTHORS: - Kira Cozzolino et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Hyperactive interferon (IFN) signaling is a hallmark of Down syndrome (DS), a condition caused by trisomy 21 (T21); strategies that normalize IFN signaling could benefit this population. Mediator-associated kinases CDK8 and CDK19 drive inflammatory responses through incompletely understood mechanisms. Using sibling-matched cell lines with/without T21, we investigated Mediator kinase function in the context of hyperactive IFN in DS. Using both targeted and unbiased, discovery-based approaches, we identified new and diverse mechanisms by which Mediator kinases regulate IFN signaling. Beyond effects on IFN-stimulated transcripts, we discovered that CDK8/CDK19 impact splicing, revealing a novel means by which Mediator kinases control gene expression. Kinase inhibition altered splicing in pathway-specific ways and selectively disrupted IFN-responsive gene splicing in T21 cells. Moreover, Mediator kinase inhibition blocked cytokine responses to IFNγ and severely impacted core metabolic pathways, including up-regulation of anti-inflammatory lipid signaling molecules during IFNγ-stimulation. These lipids included ligands for nuclear receptors and G-protein coupled receptors that can act in an autocrine or paracrine manner, suggesting additional kinase-dependent mechanisms to durably suppress IFNγ responses, beyond initial changes in gene expression. Collectively, our results establish that Mediator kinase inhibition antagonizes IFNγ signaling through transcriptional, metabolic, and cytokine responses, with implications for DS and other chronic inflammatory conditions. Significance: As Mediator-associated kinases, CDK8 and CDK19 are established regulators of RNA polymerase II transcription; however, the "downstream" biochemical impacts of CDK8/CDK19 inhibition have not been thoroughly examined. We previously showed that CDK8 and CDK19 help activate transcriptional responses to the universal cytokine IFNγ; others have demonstrated that Down syndrome (

Neurobiology - Neurobiología

TÍTULO / TITLE:   - Editorial: Current advances in the study of Down Syndrome: From development to aging

REVISTA / JOURNAL:    - Front Neurosci 2023 Mar 20;17:1161147. doi: 10.3389/fnins.2023.1161147. eCollection 2023

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AUTORES / AUTHORS: - Aaron Johnstone, William Mobley

INSTITUCIÓN / INSTITUTION: - University of California, San Diego, La Jolla, CA, United States 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Retromer Stabilization Improves Cognitive Function and Synaptic Plasticity in a Mouse Model of Down Syndrome

REVISTA / JOURNAL:    - J Alzheimers Dis. 2023;94(2):513-518. doi: 10.3233/JAD-230205

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AUTORES / AUTHORS: - Mary Elizabeth Curtis

INSTITUCIÓN / INSTITUTION: - Alzheimers Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA 

RESUMEN / SUMMARY: - Background: Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects and inversely correlate with the Alzheimers disease-like neuropathology. However, whether targeting in vivo the retromer system affects cognitive deficits and synaptic function in Down syndrome remains unknown. Objective: The aim of the current study was to examine the effects of pharmacological retromer stabilization on cognitive and synaptic functions in a mouse model of Down syndrome. Methods: Ts65dn mice were administered the pharmacological chaperone, TPT-172, or vehicle from 4 to 9 months of age and then assessed for changes in cognitive function. To assess the effects of TPT-172 on synaptic plasticity, hippocampal slices from Ts65dn mice were incubated in TPT-172 and used for field potential recordings. Results: Chronic TPT-172 treatment improved performance in cognitive function tests, its incubation with hippocampal slices ameliorated synaptic function response. Conclusion: Pharmacological stabilization of the retromer complex improves synaptic plasticity and memory in a mouse model of Down syndrome. These results support the therapeutic potential of pharmacological retromer stabilization for individual with Down syndrome.

TÍTULO / TITLE:   - Single-nucleus profiling identifies accelerated oligodendrocyte precursor cell senescence in a mouse model of Down Syndrome

REVISTA / JOURNAL:    - eNeuro. 2023 Jul 24;ENEURO.0147-23.2023. doi: 10.1523/ENEURO.0147-23.2023. Online ahead of print

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AUTORES / AUTHORS: - Bianca Rusu et al

INSTITUCIÓN / INSTITUTION: - Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1A8, Canada 

RESUMEN / SUMMARY: - Down Syndrome (DS), the most common genetic cause of intellectual disability, is associated with lifelong cognitive deficits. However, the mechanisms by which triplication of chromosome 21 genes drive neuroinflammation and cognitive dysfunction are poorly understood. Here, using the Ts65Dn mouse model of DS, we performed an integrated single-nucleus ATAC and RNA-sequencing (snATAC-seq and snRNA-seq) analysis of the adult cortex. We identified cell type-specific transcriptional and chromatin-associated changes in the Ts65Dn cortex, including regulators of neuroinflammation, transcription and translation, myelination, and mitochondrial function. We discovered enrichment of a senescence-associated transcriptional signature in Ts65Dn oligodendrocyte precursor cells (OPCs) and epigenetic changes consistent with a loss of heterochromatin. We found that senescence is restricted to a subset of OPCs concentrated in deep cortical layers. Treatment of Ts65Dn mice with a senescence-reducing flavonoid rescued cortical OPC proliferation, restored microglial homeostasis, and improved contextual fear memory. Together, these findings suggest that cortical OPC senescence may be an important driver of neuropathology in DS. SIGNIFICANCE STATEMENT Down Syndrome (DS) is the most common genetic cause of intellectual disability worldwide, is characterized by chronic neuroinflammation, and results in a ubiquitous incidence of early-onset neurodegeneration. Here, we conduct single-nucleus multi-omic profiling of the mature adult cortex of an established mouse model of DS, and systematically identify key perturbations in pathways critical for neurogenesis, myelination, and neuroinflammation. We discover the enrichment of a senescence- associated gene signature in trisomic cortical oligodendrocyte precursor cells (OPCs), validate our computational findings using orthogonal approaches, and show that a senescence-reducing flavonoid significantly improves memory deficits. Our findings suggest tha

TÍTULO / TITLE:   - Increased propensity for infantile spasms and altered neocortical excitation-inhibition balance in a mouse model of Down syndrome carrying human chromosome 21

REVISTA / JOURNAL:    - Neurobiol Dis. 2023 Aug;184:106198. doi: 10.1016/j.nbd.2023.106198. Epub 2023 Jun 13.

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AUTORES / AUTHORS: - Li-Rong Shao et al

INSTITUCIÓN / INSTITUTION: - Division of Pediatric Neurology, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 

RESUMEN / SUMMARY: - Children with Down syndrome (DS, trisomy of chromosome 21) have an increased risk of infantile spasms (IS). As an epileptic encephalopathy, IS may further impair cognitive function and exacerbate neurodevelopmental delays already present in children with DS. To investigate the pathophysiology of IS in DS, we induced IS-like epileptic spasms in a genetic mouse model of DS that carries human chromosome 21q, TcMAC21, the animal model most closely representing gene dosage imbalance in DS. Repetitive extensor/flexor spasms were induced by the GABAB receptor agonist γ-butyrolactone (GBL) and occurred predominantly in young TcMAC21 mice (85%) but also in some euploid mice (25%). During GBL application, background electroencephalographic (EEG) amplitude was reduced, and rhythmic, sharp-and-slow wave activity or high-amplitude burst (epileptiform) events emerged in both TcMAC21 and euploid mice. Spasms occurred only during EEG bursts, but not every burst was accompanied by a spasm. Electrophysiological experiments revealed that basic membrane properties (resting membrane potential, input resistance, action-potential threshold and amplitude, rheobase, input-output relationship) of layer V pyramidal neurons were not different between TcMAC21 mice and euploid controls. However, excitatory postsynaptic currents (EPSCs) evoked at various intensities were significantly larger in TcMAC21 mice than euploid controls, while inhibitory postsynaptic currents (IPSCs) were similar between the two groups, resulting in an increased excitation-inhibition (E-I) ratio. These data show that behavioral spasms with epileptic EEG activity can be induced in young TcMAC21 DS mice, providing proof-of-concept evidence for increased IS susceptibility in these DS mice. Our findings also show that basic membrane properties are similar in TcMAC21 and euploid mice, while the neocortical E-I balance is altered to favor increased excitation in TcMAC21 mice, which may predispose to IS generation.

TÍTULO / TITLE:   - Changes in working memory induced by lipopolysaccharide administration in mice are associated with metabotropic glutamate receptors 5 and contrast with changes induced by cyclooxygenase-2: Involvem

REVISTA / JOURNAL:    - Neuropeptides. 2023 Aug;100:102347. doi: 10.1016/j.npep.2023.102347. Epub 2023 May 9.

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AUTORES / AUTHORS: - Katarzyna Stachowicz et al

INSTITUCIÓN / INSTITUTION: - Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.  

RESUMEN / SUMMARY: - The strength and quality of the signal propagated by the glutamate synapse (Glu) depend, among other things, on the structure of the postsynaptic part and the quality of adhesion between the interacting components of the synapse. Postsynaptic density protein 95 (PSD95), mammalian target of rapamycin (mTOR), and Down syndrome cell adhesion molecule (DSCAM) are components of the proper functioning of an excitatory synapse. PSD95 is a member of the membrane-associated guanylate kinases protein family, mainly located at the postsynaptic density of the excitatory synapse. PSD95, via direct interaction, regulates the clustering and functionality of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptors at a synapse. Here, the effects of treatment with an antagonist of mGluR5 (MTEP) and NS398 (cyclooxygenase-2, COX-2 inhibitor) on PSD95, mTOR, and DSCAM in the hippocampus (HC) of C57B1/6 J mice using Western blots in the context of learning were examined. Moreover, the sensitivity of selected proteins to lipopolysaccharide (LPS) was monitored. MTEP injected for seven days induced upregulation of PSD95 in HC of mice. The observed effect was regulated by a COX-2 inhibitor and concurrently by LPS. Accompanying alterations in DSCAM protein were found, suggesting changes in adhesion strength after modulation of glutamatergic (Glu) synapse via tested compounds.

TÍTULO / TITLE:   - TempShift Reveals the Sequential Development of Human Neocortex and Skewed Developmental Timing of Down Syndrome Brains

REVISTA / JOURNAL:    - Brain Sci. 2023 Jul 13;13(7):1070. doi: 10.3390/brainsci13071070.

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AUTORES / AUTHORS: - Yuqiu Zhou et al

INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science and Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200032, China. 

RESUMEN / SUMMARY: - Development is a complex process involving precise regulation. Developmental regulation may vary in tissues and individuals, and is often altered in disorders. Currently, the regulation of developmental timing across neocortical areas and developmental changes in Down syndrome (DS) brains remain unclear. The changes in regulation are often accompanied by changes in the gene expression trajectories, which can be divided into two scenarios: (1) changes of gene expression trajectory shape that reflect changes in cell type composition or altered molecular machinery; (2) temporal shift of gene expression trajectories that indicate different regulation of developmental timing. Therefore, we developed an R package TempShift to separates these two scenarios and demonstrated that TempShift can distinguish temporal shift from different shape (DiffShape) of expression trajectories, and can accurately estimate the time difference between multiple trajectories. We applied TempShift to identify sequential gene expression across 11 neocortical areas, which suggested sequential occurrence of synapse formation and axon guidance, as well as reconstructed interneuron migration pathways within neocortex. Comparison between healthy and DS brains revealed increased microglia, shortened neuronal migration process, and delayed synaptogenesis and myelination in DS. These applications also demonstrate the potential of TempShift in understanding gene expression temporal dynamics during different biological processes.

TÍTULO / TITLE:   - A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring

REVISTA / JOURNAL:    - PLoS Biol. 2023 Jul 6;21(7):e3002197. doi: 10.1371/journal.pbio.3002197. eCollection 2023 Jul.

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AUTORES / AUTHORS: - Haiyang Dong et al

INSTITUCIÓN / INSTITUTION: - MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China 

RESUMEN / SUMMARY: - Drosophila melanogaster Down syndrome cell adhesion molecule 1 (Dscam1) encodes 19,008 diverse ectodomain isoforms via the alternative splicing of exon 4, 6, and 9 clusters. However, whether individual isoforms or exon clusters have specific significance is unclear. Here, using phenotype-diversity correlation analysis, we reveal the redundant and specific roles of Dscam1 diversity in neuronal wiring. A series of deletion mutations were performed from the endogenous locus harboring exon 4, 6, or 9 clusters, reducing to 396 to 18,612 potential ectodomain isoforms. Of the 3 types of neurons assessed, dendrite self/non-self discrimination required a minimum number of isoforms (approximately 2,000), independent of exon clusters or isoforms. In contrast, normal axon patterning in the mushroom body and mechanosensory neurons requires many more isoforms that tend to associate with specific exon clusters or isoforms. We conclude that the role of the Dscam1 diversity in dendrite self/non-self discrimination is nonspecifically mediated by its isoform diversity. In contrast, a separate role requires variable domain- or isoform-related functions and is essential for other neurodevelopmental contexts, such as axonal growth and branching. Our findings shed new light on a general principle for the role of Dscam1 diversity in neuronal wiring.

TÍTULO / TITLE:   - Single-cell RNA sequencing of neural stem cells derived from human trisomic iPSCs reveals the abnormalities during neural differentiation of Down syndrome

REVISTA / JOURNAL:    - Front Mol Neurosci. 2023 Jun 15;16:1137123. doi: 10.3389/fnmol.2023.1137123. eCollection 2023.

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AUTORES / AUTHORS: - Jia-Jun Qiu et al

INSTITUCIÓN / INSTITUTION: - Shanghai Childrens Hospital, Shanghai Institute of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 

RESUMEN / SUMMARY: - Introduction: Down syndrome (DS) is the most common genetic condition that causes intellectual disability in humans. The molecular mechanisms behind the DS phenotype remain unclear. Therefore, in this study, we present new findings on its molecular mechanisms through single-cell RNA sequencing. Methods: Induced pluripotent stem cells (iPSCs) from the patients with DS and the normal control (NC) patients were differentiated into iPSCs-derived neural stem cells (NSCs). Single-cell RNA sequencing was performed to achieve a comprehensive single-cell level differentiation roadmap for DS-iPSCs. Biological experiments were also performed to validate the findings. Results and discussion: The results demonstrated that iPSCs can differentiate into NSCs in both DS and NC samples. Furthermore, 19,422 cells were obtained from iPSC samples (8,500 cells for DS and 10,922 cells for the NC) and 16,506 cells from NSC samples (7,182 cells for DS and 9,324 cells for the NC), which had differentiated from the iPSCs. A cluster of DS-iPSCs, named DS-iPSCs-not differentiated (DSi-PSCs-ND), which had abnormal expression patterns compared with NC-iPSCs, were demonstrated to be unable to differentiate into DS-NSCs. Further analysis of the differentially expressed genes revealed that inhibitor of differentiation family (ID family) members, which exhibited abnormal expression patterns throughout the differentiation process from DS-iPSCs to DS-NSCs, may potentially have contributed to the neural differentiation of DS-iPSCs. Moreover, abnormal differentiation fate was observed in DS-NSCs, which resulted in the increased differentiation of glial cells, such as astrocytes, but decreased differentiation into neuronal cells. Furthermore, functional analysis demonstrated that DS-NSCs and DS-NPCs had disorders in axon and visual system development. The present study provided a new insight into the pathogenesis of DS.

TÍTULO / TITLE:   - How to study sleep apneas in mouse models of human pathology

REVISTA / JOURNAL:    - J Neurosci Methods. 2023 Jul 15;395:109923. doi: 10.1016/j.jneumeth.2023.109923. Epub 2023 Jul 17.

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AUTORES / AUTHORS: - Sara Alvente et al

INSTITUCIÓN / INSTITUTION: - PRISM Lab, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy 

RESUMEN / SUMMARY: - Sleep apnea, the most widespread sleep-related breathing disorder (SBD), consists of recurrent episodes of breathing cessation during sleep. This condition can be classified as either central (CSA) or obstructive (OSA) sleep apnea, with the latest being the most common and toxic. Due to the complexity of living organisms, animal models and, particularly, mice still represent an essential tool for the study of SBD. In the present review we first discuss the methodological pros and cons in the use of whole-body plethysmography to coupling respiratory and sleep measurements and to characterize CSA and OSA in mice; then, we draw an updated and objective picture of the methods used so far in the study of sleep apnea in mice. Most of the studies present in the literature used intermittent hypoxia to mimic OSA in mice and to investigate consequent pathological correlates. On the contrary, few studies using genetic manipulation or high-fat diets investigated the pathogenesis or potential treatments of sleep apnea. To date, mice lacking orexins, hemeoxygenase-2, monoamine oxidase A, Phox2b or Cdkl5 can be considered validated mouse models of sleep apnea. Moreover, genetically- or diet-induced obese mice, and mice recapitulating Down syndrome were proposed as OSA models. In conclusion, our review shows that despite the growing interest in the field and the need of new therapeutical approaches, technical complexity and inter-study variability strongly limit the availability of validated mouse of sleep apnea, which are essential in biomedical research.

Neurology - Neurología

TÍTULO / TITLE:   - De novo progressive dural arteriovenous fistula with putamen hemorrhage associated with long-term Down syndrome: A case report and literature review

REVISTA / JOURNAL:    - Radiol Case Rep. 2023 Apr 29;18(7):2329-2334. doi: 10.1016/j.radcr.2023.04.009. eCollection 2023 Ju

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AUTORES / AUTHORS: - Fukutaro Ohgaki et al

INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. 

RESUMEN / SUMMARY: - Dural arteriovenous fistula (DAVF) is considered an acquired change in blood flow related to factors such as craniotomy, trauma, and infection. However, several factors related to its development remain unknown. Here, we present a case of a 48-year-old man with Down syndrome and Eisenmenger syndrome. He had a history of craniotomy for multiple brain abscesses, followed by the occurrence of a de novo straight sinus (StS) DAVF within the last 2 years. The patient presented with right putamen hemorrhage due to venous congestion by a StS DAVF. The shunt flow was occluded by transarterial embolization using Onyx. Several studies have reported on DAVF models induced by venous congestion and hypoxemia. In this case, local venous congestion due to craniotomy for multiple brain abscesses was considered as one of the causes of DAVF. Complication of venous thrombosis or chronic hypoxemia due to Eisenmenger syndrome might have led to its progression. Especially in DAVF cases with Down syndrome, concomitant symptoms such as hypoxemia due to congenital heart failure and coagulopathy could worsen the disease state progressively.

TÍTULO / TITLE:   - TempShift Reveals the Sequential Development of Human Neocortex and Skewed Developmental Timing of Down Syndrome Brains

REVISTA / JOURNAL:    - Brain Sci. 2023 Jul 13;13(7):1070. doi: 10.3390/brainsci13071070.

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AUTORES / AUTHORS: - Yuqiu Zhou et al

INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science and Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200032, China. 

RESUMEN / SUMMARY: - Development is a complex process involving precise regulation. Developmental regulation may vary in tissues and individuals, and is often altered in disorders. Currently, the regulation of developmental timing across neocortical areas and developmental changes in Down syndrome (DS) brains remain unclear. The changes in regulation are often accompanied by changes in the gene expression trajectories, which can be divided into two scenarios: (1) changes of gene expression trajectory shape that reflect changes in cell type composition or altered molecular machinery; (2) temporal shift of gene expression trajectories that indicate different regulation of developmental timing. Therefore, we developed an R package TempShift to separates these two scenarios and demonstrated that TempShift can distinguish temporal shift from different shape (DiffShape) of expression trajectories, and can accurately estimate the time difference between multiple trajectories. We applied TempShift to identify sequential gene expression across 11 neocortical areas, which suggested sequential occurrence of synapse formation and axon guidance, as well as reconstructed interneuron migration pathways within neocortex. Comparison between healthy and DS brains revealed increased microglia, shortened neuronal migration process, and delayed synaptogenesis and myelination in DS. These applications also demonstrate the potential of TempShift in understanding gene expression temporal dynamics during different biological processes.

TÍTULO / TITLE:   - Correlating MRI-based brain volumetry and cognitive assessment in people with Down syndrome

REVISTA / JOURNAL:    - Brain Behav. 2023 Jul 26;e3186. doi: 10.1002/brb3.3186. Online ahead of print

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AUTORES / AUTHORS: - Osama Hamadelseed, Thomas Skutella

INSTITUCIÓN / INSTITUTION: - Department of Neuroanatomy, Institute of Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany 

RESUMEN / SUMMARY: - Introduction: Down syndrome (DS) is the most common genetic cause of intellectual disability. Children and adults with DS show deficits in language performance and explicit memory. Here, we used magnetic resonance imaging (MRI) on children and adults with DS to characterize changes in the volume of specific brain structures involved in memory and language and their relationship to features of cognitive-behavioral phenotypes. Methods: Thirteen children and adults with the DS phenotype and 12 age- and gender-matched healthy controls (age range 4-25) underwent an assessment by MRI and a psychological evaluation for language and cognitive abilities. Results: The cognitive profile of people with DS showed deficits in different cognition and language domains correlating with reduced volumes of specific regional and subregional brain structures, confirming previous related studies. Interestingly, in our study, people with DS also showed more significant parahippocampal gyrus volumes, in agreement with the results found in earlier reports. Conclusions: The memory functions and language skills affected in studied individuals with DS correlate significantly with the reduced volume of specific brain regions, allowing us to understand DSs cognitive-behavioral phenotype. Our results provide an essential basis for early intervention and the design of rehabilitation management protocols.

Ophtalmology - Oftalmología

TÍTULO / TITLE:   - The Ophthalmic Manifestations of Down Syndrome

REVISTA / JOURNAL:    - Children (Basel). 2023 Feb 9;10(2):341. doi: 10.3390/children10020341.

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AUTORES / AUTHORS: - Emily Sun, Courtney L Kraus

INSTITUCIÓN / INSTITUTION: - Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD 21218, USA. 

RESUMEN / SUMMARY: - Down Syndrome is one of the most common chromosomal conditions in the world, affecting an estimated 1:400-1:500 births. It is a multisystem genetic disorder but has a wide range of ophthalmic findings. These include strabismus, amblyopia, accommodation defects, refractive error, eyelid abnormalities, nasolacrimal duct obstruction, nystagmus, keratoconus, cataracts, retinal abnormalities, optic nerve abnormalities, and glaucoma. These ophthalmic conditions are more prevalent in children with Down Syndrome than the general pediatric population, and without exception, early identification with thoughtful screening in this patient population can drastically improve prognosis and/or quality of life.

TÍTULO / TITLE:   - Snowflake cataract in Downs syndrome

REVISTA / JOURNAL:    - Pan Afr Med J. 2023 Jan 6;44:13. doi: 10.11604/pamj.2023.44.13.37833. eCollection 2023.

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AUTORES / AUTHORS: - Rasika Bagewadi, Sachin Daigavane

INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi (Meghe), Wardha, Maharashtra, India. 

RESUMEN / SUMMARY: -

Orthopedics - Ortopedía

TÍTULO / TITLE:   - Is There a Relationship Between the Functional Level of Juvenile and Adolescent Patients With Down Syndrome and Hip Dysplasia?

REVISTA / JOURNAL:    - J Pediatr Orthop. 2023 May-Jun;43(5):e311-e318. doi: 10.1097/BPO.0000000000002370. Epub 2023 Feb 20

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AUTORES / AUTHORS: - Maria Galan-Olleros et al

INSTITUCIÓN / INSTITUTION: - Neuro-Orthopaedic Unit. Hospital Infantil Universitario Niño Jesus. 

RESUMEN / SUMMARY: - Background: The prevalence of hip dysplasia among patients with Down syndrome (DS) is higher than in the general population. We hypothesize that a relationship may exist between functional level and hip dysplasia in DS, but this has not been studied to date. The aim of this study is to evaluate whether there is a relationship between functional level and radiographic parameters of hip dysplasia or other measures. Methods: Retrospective cross-sectional comparative study of 652 patients with DS from a pediatric referral center database. Patients over 8 years of age with an anteroposterior pelvis radiograph and with no exclusion criteria were selected, totaling 132 patients (264 hips; 54.55% females; mean age 12.96 ± 2.87 y). Several radiographic parameters of the acetabulum [Sharp angle (SA), Tönnis angle (TA), Wiberg center-edge angle (W-CEA), extrusion index (EI), and acetabular retroversion signs], the proximal femur [neck shaft angle (NSA)], and joint congruence [Shenton line (SL)] were assessed. Patients were classified into 2 levels based on functional skills. A multivariate association analysis was performed between radiographic parameters and functional level. Results: Sixty-one patients were compatible with a functional level I and 71 with a level II. Forty-six hips were dysplastic and 60 were borderline according to the W-CEA. A statistically significant relationship was found between the categorical distribution of certain radiographic measurements of hip dysplasia (EI, SA, TA, W-CEA, SL, and classification by functional level ( P < 0.0005). A significant receiver operating characteristic curve was obtained for W-CEA with a cutt-off point at 26.4 degrees for level I (area under the curve = 0.763; P < 0.005; sensitivity = 0.800 and specificity = 0.644). There was a fairly high correlation between EI and TA (0.749; P < 0.0005), EI and W-CEA (-0.817; P < 0.0005), and TA and W-CEA (-0.748; P < 0.0005). Numerous hips showed signs of acetabular retroversion, with

TÍTULO / TITLE:   - Scoliosis in Adolescent Patients With Down Syndrome: Correlation Between Curve Magnitude and Functional Level

REVISTA / JOURNAL:    - Clin Spine Surg. 2023 Jul 14. doi: 10.1097/BSD.0000000000001495. Online ahead of print.

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AUTORES / AUTHORS: - Rosa M Egea-Gamez et al

INSTITUCIÓN / INSTITUTION: - Spinal Unit, Orthopaedic Surgery and Traumatology Department. Hospital Infantil Universitario Niño Jesús. Madrid, Spain. 

RESUMEN / SUMMARY: - Study design: This is a retrospective, observational comparative study. Objective: The aim of this study is to determine whether a relationship exists between the functional level and spinal deformity in patients with Down syndrome (DS). Summary of background data: Patients with DS have a higher incidence of scoliosis than the general population; however, it is unknown whether functional level influences the characteristics and severity of the deformity. Materials and methods: Of 649 patients with DS included in a pediatric referral center database, we identified 59 with a diagnosis of scoliosis (59.32% female; mean age, 14.19±1.82 y); the 46 patients who met the inclusion criteria comprised the study cohort. According to their functional gait skills and gross motor skills, they were classified into 2 levels. Different coronal and sagittal parameters were measured using full-spine standing radiographs. The need for surgical treatment and history of thoracotomy were recorded as well. Finally, a multivariate association analysis was performed between radiologic parameters and functional level. Results: Twenty-two patients had a functional level consistent with level I and 24 with level II. Twelve curves were thoracic, 10 thoracolumbar, and 24 lumbar. A statistically significant relationship was found between functional level I and II and curve magnitude: 18.9 degrees (6.8) versus 36.9 degrees (20.3) (P=0.001) with a cutoff point at 22.3 degrees (area under the curve=0.919, P<0.005, sensitivity=0.917 and specificity=0.818). The relationship between patients who required surgery and level II was also significant (P=0.016). No relationship was found between functional level and coronal and sagittal balance, nor with other radiologic parameters or with curve location, or between the history of thoracotomy and thoracic curves. Conclusions: DS adolescents with poorer functional level were associated with larger curves and greater risk for surgery. These findings may provid

Physiotherapy - Fisioterapia

TÍTULO / TITLE:   - Sleep apnea in people with Down syndrome: Causes and effects of physical activity?

REVISTA / JOURNAL:    - Front Neurol. 2023 Feb 2;14:1123624. doi: 10.3389/fneur.2023.1123624. eCollection 2023.

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AUTORES / AUTHORS: - Duy-Thai Nguyen et al.

INSTITUCIÓN / INSTITUTION: - Clinical Research Committee, Vietnam Society of Sleep Medicine (VSSM), Da Lat, Vietnam 

RESUMEN / SUMMARY: - Poor sleep quality is recognized as a major risk factor for poor health, increasing the incidence of serious chronic diseases. In people with Down syndrome, sleep apnea prevalence is significantly greater, it is caused by genetic, anatomical, endocrine, and metabolic abnormalities. The consequences of sleep disruption due to sleep apnea are very serious, especially in terms of neurocognitive and cardiovascular effects, leading to reduced life expectancy and quality of life in this population. However, the management, care, and treatment of related disorders in people with Down syndrome are still inadequate and limited. Therefore, this article wants to increase understanding and awareness about sleep apnea and the benefits of physical activity in improving sleep quality in the Down syndrome community, families, and their care specialists.

TÍTULO / TITLE:   - Swimmers with Down Syndrome Are Healthier and Physically Fit than Their Untrained Peers

REVISTA / JOURNAL:    - Healthcare (Basel). 2023 Feb 7;11(4):482. doi: 10.3390/healthcare11040482.

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AUTORES / AUTHORS: - Ana Querido et al.

INSTITUCIÓN / INSTITUTION: - N2i, Polytechnic Institute of Maia, 4475-690 Maia, Portugal. 

RESUMEN / SUMMARY: - While there are positive benefits from physical activity participation for individuals with Down syndrome, little is known about the effects of swimming training. The aim of this study was to compare the body composition and physical fitness profile of competitive swimmers and moderately active (untrained) individuals with Down syndrome. The Eurofit Special test was applied to a group of competitive swimmers (n = 18) and a group of untrained individuals (n = 19), all with Down syndrome. In addition, measurements were taken to determine body composition characteristics. The results showed differences between swimmers and untrained subjects in height, sum of the four skinfolds, body fat %, fat mass index and all items of the Eurofit Special test. Swimmers with Down syndrome exhibited physical fitness levels near to the Eurofit standards, although lower fitness levels were attained by these persons when compared to athletes with intellectual disability. It can be concluded that the practice of competitive swimming seems to counteract the tendency for obesity in persons with Down syndrome and also helps to increase strength, speed and balance.

TÍTULO / TITLE:   - An investigation of the effects of dual-task balance exercises on balance, functional status and dual-task performance in children with Down syndrome

REVISTA / JOURNAL:    - Dev Neurorehabil. 2023 Jul 4;1-8. doi: 10.1080/17518423.2023.2233031. Online ahead of print

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AUTORES / AUTHORS: - Neslinur Merve Buyukcelik et al

INSTITUCIÓN / INSTITUTION: - Institute of Graduate Programs, Department of Physiotherapy and Rehabilitation, Hasan Kalyoncu University, Gaziantep, Turkey 

RESUMEN / SUMMARY: - Purpose: To investigate the effects of dual task (DT) balance exercises on functional status, balance, and DT performance in children with Down Syndrome (DS). Methods: Participants were divided into two groups: intervention group (IG; n = 13) and control group (CG;n = 14). WeeFIM was used to measure the functional independence level and balance was evaluated using the Pediatric Balance Scale. DT performance was assessed using Timed Up and Go, Single Leg Stance, Tandem-Stance and 30 s Sit to Stand tests without concomitant task, with motor task or cognitive task. The IG received 16 sessions of DT training twice a week for 8 weeks. Results: Functional level, balance, and DT performance improved significantly in the IG, whereas only balance improved in the CG. Significantly better results were achieved in the IG, as demonstrated by greater pre/post-treatment changes. Conclusion: DT balance exercises improved functional level, balance and DT performance of children with DS.

TÍTULO / TITLE:   - The association of increased body mass index on cardiorespiratory fitness, physical activity, and cognition in adults with down syndrome

REVISTA / JOURNAL:    - Disabil Health J. 2023 Jun 16;101497. doi: 10.1016/j.dhjo.2023.101497. Online ahead of print.

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AUTORES / AUTHORS: - Danica Dodd et al

INSTITUCIÓN / INSTITUTION: - School of Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA; Department of Internal Medicine, The University of 

RESUMEN / SUMMARY: - Background: Obesity is a significant risk factor for Alzheimers disease; however, this association has not been explored in adults with Down syndrome. Objective: To examine the association of obesity, assessed by body mass index (BMI), with factors related to Alzheimers disease risk including cardiorespiratory fitness, physical activity, and cognition in adults with Down syndrome. Methods: Adults with Down syndrome attended a laboratory visit where BMI, cardiorespiratory fitness (VO2 peak), and cognitive function (CANTAB® DS Battery) were obtained. Physical activity (accelerometer) was collected over the week following the laboratory visit. Wilcoxon rank sum tests were used to evaluate differences in cardiorespiratory fitness, sedentary time, moderate-to-vigorous physical activity (MVPA), and cognition between adults with obesity (BMI≥ 30 kg/m2) and those with healthy weight or overweight (BMI <30 kg/m2). Spearman correlations and linear regressions were used to measure the impact of BMI on cardiorespiratory fitness, MVPA, sedentary time, and cognition. Results: Data was collected for 79 adults with Down syndrome (26.7 ± 9.0 years of age, 54% female, 54% with obesity). VO2 peak was significantly lower in participants with obesity (18.4 ± 2.5 ml/kg/min) compared to those with healthy weight or overweight (22.9 ± 4.0 ml/kg/min, p < 0.001). BMI was negatively associated with cardiorespiratory fitness (rho = -0.614, p < 0.001). No associations were observed between BMI and physical activity or cognition. Conclusions: Lower BMI was associated with improved cardiorespiratory fitness. However, no associations were observed between BMI and cognition or physical activity.

TÍTULO / TITLE:   - Cognitive-motor interference during standing stance across different postural and cognitive tasks in individuals with Down syndrome

REVISTA / JOURNAL:    - Res Dev Disabil. 2023 Aug;139:104562. doi: 10.1016/j.ridd.2023.104562. Epub 2023 Jun 26.

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AUTORES / AUTHORS: - Rihab Borji et al

INSTITUCIÓN / INSTITUTION: - Research Laboratory: Education, Motricité, Sport et Santé, EM2S, LR19JS01, High Institute of Sport and Physical Education of Sfax, University of Sfax, Sfax, Tunisia.  

RESUMEN / SUMMARY: - Background: Individuals with Down syndrome (DS) presented both cognitive and motor impairments that could influence each other. Therefore, exploring cognitive-motor interference during standing stance is relevant in this population. Aims: This study explored the dual task (DT) effects on postural balance during diverse cognitive tasks and sensory manipulations in individuals with DS, compared to those with typical development (TD). Methods and procedures: Fifteen adolescents with DS (age = 14.26 ± 1.27 years; height = 1.50 ± 0.02; weight = 46.46 ± 4.03 kg; BMI =20.54 ± 1.51 kg/m2) and thirteen with TD (age = 14.07 ± 1.11 years; height = 1.50 ± 0.05; weight = 44.92 ± 4.15 kg; BMI =19.77 ± 0.94 kg/m2) participated in this study. Postural and cognitive performances for the selective span task (SST) and the verbal fluency (VF) were recorded during single task (ST) and DT conditions. Postural conditions were: firm eyes open (firm-EO), firm eyes closed (firm-EC) and foam-EO. Motor and cognitive DT costs (DTC) were calculated and analyzed across these different cognitive and postural conditions. Outcomes and results: In the DS group, postural performance was significantly (p < 0.001) altered during all DT conditions, compared to the ST situation. Moreover, the motor DTC was significantly (p < 0.001) higher while performing the VF task than the SST. However, in the control group, postural performance was significantly (p < 0.001) impaired only while performing the VF test in the DT-Firm EO condition. For both groups, cognitive performances were significantly (p < 0.05) altered in all DT conditions compared to the ST one. Conclusion: Adolescents with DS are more prone to DT effects on postural balance than those with TD.

TÍTULO / TITLE:   - Development of a Physical Therapy-Based Exercise Program for Adults with Down Syndrome

REVISTA / JOURNAL:    - Int J Environ Res Public Health. 2023 Feb 18;20(4):3667. doi: 10.3390/ijerph20043667.

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AUTORES / AUTHORS: - Sarah Mann et al

INSTITUCIÓN / INSTITUTION: - Mann Method PT and Fitness, Arvada, CO 80005, USA. 

RESUMEN / SUMMARY: - In adults with Down syndrome, the combination of low physical activity and fitness levels and the high prevalence of musculoskeletal co-morbidities stresses the need for specialized exercise programs. The goal of this research study was to develop a specialized exercise program for individuals with Down syndrome using the physical therapy approach of a systems review as the foundation. We first conducted an overview of the literature on co-morbidities in adults with Down syndrome using the systems review method to categorize these findings. We extracted recommendations for content and delivery of an exercise program based on the literature review, and finally composed a specialized exercise program for individuals with Down syndrome adhering to these recommendations.

TÍTULO / TITLE:   - A slightly adapted treadmill protocol for the determination of maximal oxygen uptake in adults with Down syndrome

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2023 Jun 29. doi: 10.1111/jar.13138. Online ahead of print.

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AUTORES / AUTHORS: - Pieter-Henk Boer

INSTITUCIÓN / INSTITUTION: - Department of Human Movement Science, Cape Peninsula University of Technology, Wellington, South Africa 

RESUMEN / SUMMARY: - Introduction: The VO2 max test is the gold standard measure for aerobic fitness. A standardised treadmill protocol was developed years ago for individuals with Down syndrome but with variations in terms of starting speed, load increases and time spent at each stage. However, we realised that the most widely used protocol for adults with Down syndrome, trouble participants with high treadmill speeds. Consequently, the purpose of the current study was to determine whether an adapted protocol provided improved maximal test performance. Method: Twelve adults (33 ± 6 years) randomly performed two variations of the standardised treadmill test. Results: The protocol that added another incremental incline stage increase yielded a significant improvement in absolute and relative VO2 peak, time to exhaustion, minute ventilation and heart rate max. Conclusion: A treadmill protocol with the addition of an incremental incline stage allowed for a significant improvement in maximal test performance.

TÍTULO / TITLE:   - Physical Training Chronically Stimulates the Motor Neuron Cell Nucleus in the Ts65Dn Mouse, a Model of Down Syndrome

REVISTA / JOURNAL:    - Cells. 2023 May 27;12(11):1488. doi: 10.3390/cells12111488.

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AUTORES / AUTHORS: - Chiara Rita Inguscio et al

INSTITUCIÓN / INSTITUTION: - Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, Strada Le Grazie 8, I-37134 Verona, Italy. 

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetically-based disease based on the trisomy of chromosome 21 (Hsa21). DS is characterized by intellectual disability in association with several pathological traits among which early aging and altered motor coordination are prominent. Physical training or passive exercise were found to be useful in counteracting motor impairment in DS subjects. In this study we used the Ts65Dn mouse, a widely accepted animal model of DS, to investigate the ultrastructural architecture of the medullary motor neuron cell nucleus taken as marker of the cell functional state. Using transmission electron microscopy, ultrastructural morphometry, and immunocytochemistry we carried out a detailed investigation of possible trisomy-related alteration(s) of nuclear constituents, which are known to vary their amount and distribution as a function of nuclear activity, as well as the effect of adapted physical training upon them. Results demonstrated that trisomy per se affects nuclear constituents to a limited extent; however, adapted physical training is able to chronically stimulate pre-mRNA transcription and processing activity in motor neuron nuclei of trisomic mice, although to a lesser extent than in their euploid mates. These findings are a step towards understanding the mechanisms underlying the positive effect of physical activity in DS.

TÍTULO / TITLE:   - Analysis of Heart Rate, Perception of Physical Effort and Performance of Individuals with Down Syndrome Submitted to a Protocol of Virtual Games for Home-Based Telerehabilitation

REVISTA / JOURNAL:    - Healthcare (Basel). 2023 Jun 30;11(13):1894. doi: 10.3390/healthcare11131894

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AUTORES / AUTHORS: - Renata Martins Rosa et al

INSTITUCIÓN / INSTITUTION: - Postgraduate Program in Rehabilitation Sciences, Faculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 01246-903, SP, Brazil. 

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetic condition associated with impairments in several body systems, which may negatively influence the habit of practicing physical activities (PAs), increasing sedentary habits and the risk of comorbidities. Additionally, difficulty in accessing services, financial limitations and lack of interest may interfere with the practice of PAs. Considering the necessity of developing effective treatment alternatives, to increase the possibility of access and the interest of participants, we conducted a study using telerehabilitation with a virtual task to promote PA and analyze the motor performance of DS individuals. Our protocol consisted of 11 sessions of the virtual game called MoveHero. A total of 34 individuals with DS and 34 individuals with typical development participated in the study. Heart rate (HR) and rating of perceived effort (RPE) were collected at rest and during the game. Our results show that virtual reality presents a great possibility to promote PA and a way out of a sedentary lifestyle for DS individuals, considering the enhancement in HR and RPE found during the protocol for both groups. Moreover, our results show positive outcomes regarding motor performance, with significant improvement in the task with practice, demonstrating that individuals with DS are able to improve their motor proficiency with adequate stimuli in the virtual environment.

TÍTULO / TITLE:   - Physical training promotes remodeling of the skeletal muscle extracellular matrix: An ultrastructural study in a murine model of Down syndrome

REVISTA / JOURNAL:    - Microsc Res Tech. 2023 Jun 28. doi: 10.1002/jemt.24379. Online ahead of print

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AUTORES / AUTHORS: - Barbara Cisterna et al

INSTITUCIÓN / INSTITUTION: - Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. 

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetically based disease caused by triplication of chromosome 21. DS is characterized by multi-systemic premature aging associated with deficit in motor coordination, balance, and postural control. Using a morphological, morphometrical, and immunocytochemical ultrastructural approach, this study investigated in vastus lateralis muscle of Ts65Dn mouse, a murine model of DS, the effect of an adapted physical training on the extracellular matrix (ECM) characteristics and whether the forecasted exercise-induced ECM remodeling impacts on sarcomere organization. Morphometry demonstrated thicker basement membrane and larger collagen bundles with larger interfibrillar spacing as well as irregularly arrayed myofibrils and lower telethonin density on Z-lines in trisomic versus euploid sedentary mice. In agreement with the multi-systemic premature aging described in DS, these ECM alterations were similar to those previously observed in skeletal muscle of aged mice. Adapted physical training induced remodeling of ECM in both trisomic and euploid mice, that is, enlargement of the collagen bundles associated with hypertrophy of collagen fibrils and reduction of the interfibrillar spacing. A re-alignment of the myofibrils and a higher telethonin density on Z-line was found in trisomic mice. Altogether, our findings suggest that physical training is an effective tool in limiting/counteracting the trisomy-associated musculoskeletal structural anomalies. The current findings constitute a solid experimental background for further study investigating the possible positive effect of physical training on skeletal muscle performance. RESEARCH HIGHLIGHTS: Vastus lateralis muscle of trisomic mice shows aging-like alterations of extracellular matrix. Training promotes extracellular matrix remodeling. Training may be an effective tool to counteract trisomy-associated alterations of skeletal muscle.

Prenatal diagnosis - Diagnóstico

TÍTULO / TITLE:   - Impact of a prenatal screening program on the Down syndrome phenotype: An interrupted time series analysis

REVISTA / JOURNAL:    - Acta Obstet Gynecol Scand. 2023 Jun;102(6):751-759. doi: 10.1111/aogs.14573. Epub 2023 Apr 25.

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AUTORES / AUTHORS: - Ellen Hollands Steffensen

INSTITUCIÓN / INSTITUTION: - Center for Fetal Diagnostics, Aarhus University, Aarhus, Denmark 

RESUMEN / SUMMARY: - Introduction: We hypothesized that children with Down syndrome who were born after the implementation of first-trimester combined screening for trisomy 13, 18, and 21 and a second-trimester ultrasound scan in Denmark would show a milder syndrome phenotype. We investigated the birth biometry, prevalence of congenital malformations, and early childhood morbidity of children with Down syndrome before and after implementation of this screening program. Material and methods: A nationwide register-based study of all live born singletons with Down syndrome in Denmark from 1995 to 2018. In interrupted time series analyses, we studied the temporal developments in birth biometry, prevalence of congenital malformations, and early childhood morbidity related to the implementation of a national prenatal screening program. Results: We included 602 singletons with Down syndrome born before and 308 after implementation of the screening program. Z-scores of birthweight and head circumference increased over time before screening, but this temporal development changed after implementation by -0.05 (95% confidence interval [CI]: -0.11 to 0.01) and -0.05 (95% CI -0.12 to 0.02), respectively. Just after implementation, the prevalence of non-severe congenital heart disease decreased (relative change in odds 0.48 [95% CI: 0.24-0.94]). For severe congenital heart disease, atrioventricular septal defect, and non-heart malformations, this change was 1.16 (95% CI: 0.56-2.41), 0.95 (95% CI: 0.43-2.03), and 0.98 (95% CI: 0.33-2.76), respectively. For all malformations, pre-existing temporal developments did not change following implementation of screening. The implementation was associated with higher odds of admission to a neonatal intensive care unit (relative change 1.98 [95% CI: 0.76-5.26]) and an increased risk of hearing impairment (risk difference 3.4% [95% CI: -0.4% to 7.1%]). In contrast, the implementation was not associated with the incidence of hospital admissions by 2 years of age o

TÍTULO / TITLE:   - Parental psychological distress of missed diagnosis of Down syndrome at antenatal screening: a rare, but still real occurrence. a case report and review of literature

REVISTA / JOURNAL:    - Fetal Diagn Ther. 2023 Mar 25. doi: 10.1159/000530332. Online ahead of print.

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AUTORES / AUTHORS: - Pasquale Giuseppe Macri et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Introduction Prenatal screening programs are important component for pregnant women care and is often linked with grief and shock based on gestational age or the diagnosis. Lower/ no sensitivity is also associated with these screening programs leading to providing false negative outputs. Case Presentation Present work shows a case of missed antenatal diagnosis of Down syndrome and its persistent medical and psychological impact on the family members. We have also discussed the relevant economic and medical-legal issues related to the context and aimed to maintain an adequate awareness among healthcare to discuss properly these investigations (difference between screening and diagnostic testing), their possible outcome (chances of false results) and enabled the pregnant women/couple to take informed decision on in early pregnancy. Discussion/Conclusion These programs are considered as routine clinical practice in many countries from last few years, and is necessary to assess the pros and cons of these programs. One of the prime con involves the likeliness of obtaining a false negative result due to lack of 100% sensitivity and specificity.

TÍTULO / TITLE:   - "Overestimated technology - underestimated consequences" - reflections on risks, ethical conflicts, and social disparities in the handling of non-invasive prenatal tests (NIPTs)

REVISTA / JOURNAL:    - Med Health Care Philos. 2023 Jun;26(2):271-282. doi: 10.1007/s11019-023-10143-1. Epub 2023 Mar 18.

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AUTORES / AUTHORS: - Marion Baldus

INSTITUCIÓN / INSTITUTION: - Faculty of Social Work, Hochschule Mannheim / Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, Mannheim, Germany. m.baldus@hs-mannheim.de. 

RESUMEN / SUMMARY: - New technologies create new complexities. Since non-invasive prenatal tests (NIPTs) were first introduced, keeping pace with complexity constitutes an ongoing task for medical societies, politics, and practice. NIPTs analyse the chromosomes of the fetus from a small blood sample. Initially, NIPTs were targeted at detecting trisomy 21 (Down syndrome): meanwhile there are sequencing techniques capable of analysing the entire genome of the unborn child. These yield findings of unclear relevance for the childs future life, resulting in new responsibility structures and dilemmas for the parents-to-be.The industrys marketing strategies overemphasize the benefits of the tests while disregarding their consequences. This paper chooses the opposite path: starting with the underestimated consequences, it focuses on adverse developments and downsides. Disparities, paradoxes, and risks associated with NIPTs are illustrated, ethical conflicts described. Indications that new technologies developed to solve problems create new ones are examined. In the sense of critical thinking, seemingly robust knowledge is scrutinized for uncertainties and ambiguities. It analyses how the interplay between genetic knowledge and social discourse results in new dimensions of responsibility not only for parents-to-be, but also for decision-makers, authorities, and professional societies, illustrated by a review of different national policies and implementation programmes. As shown by the new NIPT policy in Norway, the consequences can be startling. Finally, a lawsuit in the United States illustrates how an agency can risk forfeiting its legitimation in connection with the inaccuracy of NIPTs.

TÍTULO / TITLE:   - Decisional conflict, anxiety, and social support among Chinese pregnant women making further prenatal testing decisions

REVISTA / JOURNAL:    - J Reprod Infant Psychol. 2023 Jul 5;1-13. doi: 10.1080/02646838.2023.2232380.

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AUTORES / AUTHORS: - Jia-Ming Xiang, Ling-Ling Gao

INSTITUCIÓN / INSTITUTION: - Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital，Central South University, Changsha, Hunan, China 

RESUMEN / SUMMARY: - Objective: This study aimed to examine decisional conflict and identify its predictors in Chinese pregnant women who were making decisions about further prenatal testing after receiving a screening result of high-risk for Down syndrome. Method: A cross-sectional study was conducted from September 2020 to July 2021 in Guangzhou, China. Two-hundred and sixty pregnant women receiving a screening result of high-risk for Down syndrome completed a questionnaire comprising the Decisional Conflict Scale, Self-rating Anxiety Scale, and Social Support Rating Scale. Results: The mean decisional conflict score was 28.8 ± 13.6, representing a moderate level. Advanced age (≥35 years), having a religious belief, not knowing about non-invasive or invasive prenatal testing, choosing NIPT for further prenatal testing, high levels of anxiety, and low levels of social support were significant predictors of decisional conflict, explaining 28.4% of its variance (F = 18.115, p < 0.001). Conclusions: The results highlighted the necessity of assessing patients decisional conflict and providing adequate interventions along the prenatal care trajectory. The results also showed that providing good support has an essential value for women by relieving their decisional conflict.

TÍTULO / TITLE:   - Factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT)

REVISTA / JOURNAL:    - Prenat Diagn. 2023 Apr;43(4):467-476. doi: 10.1002/pd.6242. Epub 2022 Sep 23.

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AUTORES / AUTHORS: - Lisanne van Prooyen Schuurman et al

INSTITUCIÓN / INSTITUTION: - Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 

RESUMEN / SUMMARY: - Objective: To investigate factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT). Method: A questionnaire study was conducted among 219 pregnant women in the Netherlands who had declined prenatal screening with NIPT (TRIDENT-2 study). Respondents were selectively recruited from three hospitals and 19 midwifery practices, primarily located in or near socioeconomically disadvantaged neighborhoods. 44.3% of the respondents were of non-Western ethnic origin and 64.4% were religious. Results: Most respondents (77.2%) found the decision to decline NIPT easy to make, and 59.8% had already made the decision before information about NIPT was offered. These respondents were more often religious, multigravida, and had adequate health literacy. The main reasons to decline NIPT were "I would never terminate my pregnancy" (57.1%) and "every child is welcome" (56.2%). For 16.9% of respondents, the out-of-pocket costs (175 euros) played a role in the decision, and the women in this group were more often nonreligious, primigravida, and had inadequate health literacy. Conclusion: The primary factors involved in the decision to decline NIPT were related to personal values and beliefs, consistent with autonomous choice. Out-of-pocket costs of NIPT hinder equal access for some pregnant women.

TÍTULO / TITLE:   - A cross-country comparison of pregnant womens decision-making and perspectives when opting for non-invasive prenatal testing in the Netherlands and Belgium

REVISTA / JOURNAL:    - Prenat Diagn. 2023 Mar;43(3):294-303. doi: 10.1002/pd.6329. Epub 2023 Feb 17.

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AUTORES / AUTHORS: - Lore Lannoo et al

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, Fetomaternal Medicine, University Hospitals Leuven, Leuven, Belgium. 

RESUMEN / SUMMARY: - Background: The Netherlands and Belgium have been among the first countries to offer non-invasive prenatal testing (NIPT) as a first-tier screening test. Despite similarities, differences exist in counseling modalities and test uptake. This study explored decision-making and perspectives of pregnant women who opted for NIPT in both countries. Methods: A questionnaire study was performed among pregnant women in the Netherlands (NL) (n = 587) and Belgium (BE) (n = 444) opting for NIPT, including measures on informed choice, personal and societal perspectives on trisomy 21, 18 and 13 and pregnancy termination. Results: Differences between Dutch and Belgian women were shown in the level of informed choice (NL: 83% vs. BE: 59%, p < 0.001), intention to terminate the pregnancy in case of confirmed trisomy 21 (NL: 51% vs. BE: 62%, p = 0.003) and trisomy 13/18 (NL: 80% vs. BE: 73%, p = 0.020). More Belgian women considered trisomy 21 a severe condition (NL: 64% vs. BE: 81%, p < 0.001). Belgian women more frequently indicated that they believed parents are judged for having a child with trisomy 21 (BE: 42% vs. NL: 16%, p < 0.001) and were less positive about quality of care and support for children with trisomy 21 (BE: 23% vs. NL: 62%, p < 0.001). Conclusion: Differences in womens decision-making regarding NIPT and the conditions screened for may be influenced by counseling aspects and country-specific societal and cultural contexts.

TÍTULO / TITLE:   - Expressivist objections to prenatal screening and testing: Perceptions of people living with disability

REVISTA / JOURNAL:    - Sociol Health Illn. 2023 Jul;45(6):1223-1241. doi: 10.1111/1467-9566.13559. Epub 2022 Oct 1.

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AUTORES / AUTHORS: - Felicity Boardman, Gareth Thomas

INSTITUCIÓN / INSTITUTION: - Warwick Medical School, University of Warwick, Coventry, UK 

RESUMEN / SUMMARY: - The expressivist objection (EO) refers to the notion that using reproductive (genetic) technologies to prevent the birth of future would-be disabled people contain, and express, a negative valuation of life with disability. Whilst the EO has received increased attention in recent years in line with rapid technological and genomic developments, there remains scant research on how EO concerns are experienced and expressed by disabled people and their families, especially within and between impairment groups. Bringing together two studies -one with adults and family members living with genetic conditions (n = 62) and one with parents of children with Downs syndrome (n = 22)- we argue that disabled people and their families variously embrace, reject or rework the EO across contexts, and yet also frequently situate it within broad support for reproductive technologies. We present three key factors that mediate responses to the EO: (1) the nature of impairment and its integration within identity; (2) social and cultural contexts relating to disability and (3) the (individual and collective) imagined futures of disabled people. In so doing, we blend the conceptual architecture of medical sociology and disability studies, arguing that this allows us to accurately illuminate the nuanced responses of disabled people and their families.

TÍTULO / TITLE:   - Never "totally prepared": Support groups on helping families prepare for a child with a genetic condition

REVISTA / JOURNAL:    - J Community Genet. 2023 Jun;14(3):319-327. doi: 10.1007/s12687-023-00646-y. Epub 2023 Apr 12.

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AUTORES / AUTHORS: - Kaitlynn P Craig et al

INSTITUCIÓN / INSTITUTION: - Department of Bioethics, Case Western Reserve University School of Medicine, Cleveland, OH, USA 

RESUMEN / SUMMARY: - A rapid increase in the reach and breadth of prenatal genetic screening and testing has led to an expanding need for prenatal support of families receiving this genetic information. As part of a larger study investigating prenatal preparation for a child with a genetic condition, we interviewed representatives of patient advocacy groups (PAGs) who support parents post-diagnosis. Groups supporting families with Down syndrome were often local or regional, while other groups were often national or international in scope. Groups varied in their willingness or ability to support families prior to making a pregnancy continuation decision, and participants reflected on ways they addressed these needs with individual counseling and referrals, if needed. Participants described supporting parents with information about conditions and a range of lived experiences for families, while referring families to healthcare professionals for technical questions and additional medical needs. PAGs also prioritized connecting parents experiencing a new diagnosis with other families for peer support and community-building, both in person and on social media. Participants discussed limitations, such as a lack of racially-concordant support, ability to offer resources in languages other than English, and a lack of funding to meet the expressed needs of families post-diagnosis. Overall, participants emphasized that the parenting experience of each child is unique, irrespective of a genetic diagnosis, an experience for which parents can never be "totally prepared."

TÍTULO / TITLE:   - Non-invasive prenatal testing in Germany: a unique ethical and policy landscape

REVISTA / JOURNAL:    - Eur J Hum Genet. 2023 May;31(5):562-567. doi: 10.1038/s41431-022-01256-x. Epub 2022 Dec 12

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AUTORES / AUTHORS: - Hilary Bowman-Smart et al

INSTITUCIÓN / INSTITUTION: - Ethox Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK. 

RESUMEN / SUMMARY: - Non-invasive prenatal testing (NIPT) has been available commercially in Europe since approximately 2012. Currently, many countries are in the process of integrating NIPT into their publicly funded healthcare systems to screen for chromosomal aneuploidies such as trisomy 21 (Down syndrome), with a variety of implementation models. In 2019, the German Federal Joint Committee (G-BA), which plays a significant role in overseeing healthcare decisions in Germany, recommended that NIPT be reimbursed through public insurance. Following this recommendation, NIPT will be offered on a case-by-case basis, when a pregnant woman, after being counselled, makes an informed decision that the test is necessary in her personal situation. This model differs significantly from many other European countries, where NIPT is being implemented either as a first-tier screening offer available for all pregnancies, or a contingent screen for those with a high probability of foetal aneuploidy (with varying probability cut-offs). In this paper we examine how this unique approach to implementing NIPT in Germany is produced by an ethical and policy landscape resulting from a distinctive cultural and historical context with a significant influence on healthcare decision-making. Due in part to the specific legal and regulatory environment, as well as strong objections from various stakeholders, Germany did not implement NIPT as a first-tier screen. However, as Germany does not currently publicly fund as standard other forms of prenatal aneuploidy screening (such as combined first trimester screening), neither can it be implemented as a screen contingent on specific probability cut-offs. We discuss how German policy reflects the echoes of the past shaping approaches to new biotechnologies, and the implications of this unique model for implementing NIPT in a public healthcare system.

TÍTULO / TITLE:   - Evaluation of pre-test counselling offered for non-invasive prenatal testing (NIPT) as a primary screening tool

REVISTA / JOURNAL:    - J Obstet Gynaecol. 2023 Dec;43(1):2204959. doi: 10.1080/01443615.2023.2204959.

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AUTORES / AUTHORS: - Ho Yin Diana Lee, Lin Wai Cha

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong 

RESUMEN / SUMMARY: - The increasing popularity and expansion of non-invasive prenatal testing (NIPT) to screen for rare conditions beyond common trisomies prompts evaluation of pre-test counselling currently offered. We conducted a prospective survey to assess womens knowledge of NIPT in those who had undergone NIPT (study group) and those who were planning to have NIPT (control group). Out of the 189 questionnaires analysed, the study group did not show a higher knowledge score compared to the control group (P = 0.097). 44% misunderstood that NIPT can identify more conditions than invasive testing, 69.8% were unaware of the recommended need for nuchal translucency measurement and 52.6% were unaware of the possibility of incidental findings. 31% even considered discussing termination of pregnancy as one of the next steps if NIPT shows high risk for Down syndrome. This study shows that current pre-test counselling is inadequate. Service providers should address these knowledge gaps and assist women to make informed choices. Impact Statement What is already known on this subject? Pre-test counselling for non-invasive prenatal testing (NIPT) should be conducted to assist women in making an informed consent. What do the results of this study add? Our results show that a significant proportion of women are unaware of the limitations of NIPT. What are the implications of these findings for clinical practice and/or further research? Service providers should improve their pre-test counselling focusing on areas of knowledge deficiencies and misunderstanding on NIPT identified in this study.

Psychiatry - Psiquiatría

TÍTULO / TITLE:   - Case report: Evolution of catatonic mutism and psychotic symptoms in an adolescent with Down syndrome: transition from Down syndrome disintegrative disorder to anti-N-methyl-D-aspartate receptor encep

REVISTA / JOURNAL:    - Front Neurol. 2023 Jun 9;14:1200541. doi: 10.3389/fneur.2023.1200541. eCollection 2023.

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AUTORES / AUTHORS: - Yuki Minamisawa et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Odawara Municipal Hospital, Odawara, Japan. 

RESUMEN / SUMMARY: - During her first year of junior high school, a 12-year-old Japanese girl with Down syndrome experienced dizziness, gait disruption, paroxysmal weakness in her hands, and sluggish speaking. Regular blood tests and a brain MRI revealed no abnormalities, and she was tentatively diagnosed with adjustment disorder. Nine months later, the patient experienced a subacute sickness of chest pain, nausea, sleep problem with night terrors, and delusion of observation. Rapid deterioration then developed with simultaneous fever, akinetic mutism, loss of facial expression, and urine incontinence. These catatonic symptoms improved after a few weeks after admission and treatment with lorazepam, escitalopram, and aripiprazole. After discharge, nonetheless, daytime slumber, empty eyes, paradoxical laughter, and declined verbal communication persisted. Upon confirmation of the cerebrospinal N-methyl-D-aspartate (NMDA) receptor autoantibody, methylprednisolone pulse therapy was tried, but it had little effect. Visual hallucinations and cenesthopathy, as well as suicidal thoughts and delusions of death, have predominated in the following years. Cerebrospinal IL-1ra, IL-5, IL-15, CCL5, G-CSF, PDGFbb, and VFGF were raised in the early stage of initial medical attention with nonspecific complaints, but were less prominent in the later stages of catatonic mutism and psychotic symptoms. We suggest a disease concept of progression from Down syndrome disintegrative disorder to NMDA receptor encephalitis, based on this experience.

TÍTULO / TITLE:   - Parents Experiences of Having a Child with Down Syndrome and Sleep Difficulties

REVISTA / JOURNAL:    - Behav Sleep Med. 2023 Sep 3;21(5):570-584. doi: 10.1080/15402002.2022.2143359. Epub 2022 Nov 11

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AUTORES / AUTHORS: - Jasneek K Chawla et al

INSTITUCIÓN / INSTITUTION: - Department of Paediatric Respiratory & Sleep Medicine, Queensland Childrens Hospital, Brisbane, Australia 

RESUMEN / SUMMARY: - Objectives: Sleep disorders are prevalent in children with Down Syndrome (DS). However, sleep treatment is not always readily accessed by this group. This study aims to understand families experiences of having a child with DS and sleep difficulties, and in particular, their healthcare experiences, with the goal of informing practice improvements. Methods: We conducted semi-structured interviews with 34 parents (fathers n = 4 and mothers n = 30) with open-ended questions about parents experiences of sleep, family dynamics, and healthcare. We operationalized a reflexive Thematic Analysis. Results: Parents normalized their experiences of having a child with DS and sleep problems. Parents acknowledged that sleep disruption has adverse and pervasive impacts on their wellbeing and family dynamics, but also found this difficult to identify as a health problem. They accepted sleep difficulties as a regular part of bringing up any child, particularly one with a disability. When they did seek treatment for their childs sleep difficulties, parents often reported encountering insensitive and inadequate care and described that, at times, healthcare professionals also normalized childrens sleep difficulties, resulting in sub-optimal treatment. This included at times failure to refer to tertiary sleep medicine services when required. Conclusions: Parents and healthcare professionals normalization of sleeping difficulties denies that they are both deleterious and modifiable. Practice implications include raising healthcare professionals awareness of the importance of proactively addressing sleep, with sensitivity to families normalization strategies, recognizing that families may require prompting to report concerns.

TÍTULO / TITLE:   - Hyperphagia and Down Syndrome

REVISTA / JOURNAL:    - J Dev Behav Pediatr. 2023 Aug 1;44(6):e444-e446. doi: 10.1097/DBP.0000000000001199. Epub 2023 Jun 2

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AUTORES / AUTHORS: - Aanchal Sharma et al.

INSTITUCIÓN / INSTITUTION: - Division of Developmental Medicine, Boston Childrens Hospital, Boston, MA. 

RESUMEN / SUMMARY: - A.Z. is a 14-year-old young boy with Down syndrome and intellectual disability. As a baby and toddler, A.Z. struggled with swallowing dysfunction and recurrent aspiration, which improved by the time he was school aged. At the age of 2 years, his body mass index (BMI) was 95.98% (Z score 1.75). During his early school-age years, A.Z. began eating a wider variety of foods. As he grew taller and remained active, his BMI improved briefly during this time. Between ages 10 and 12 years, concerns regarding increased appetite and excessive weight gain emerged. His BMI increased from 82.56% (Z score 0.94) to 98.27% (Z score 2.11) during this time. He became insatiable; he ate when he was happy, upset, or bored. He had a compulsive need to eat all day, which escalated while staying home during the COVID pandemic. Despite having complete meals and a variety of snacks, he overate and sought out food and snacks, no matter the time of the day. Food also became a source of contention and a trigger for verbally and physically aggressive behavior when parents attempted to restrict food intake. Behavioral therapy was recommended to address his eating patterns as a part of his behavioral management plan.Over time, many strategies were used, including a token economy reward system, setting firm limits around snacking and meals, creating a food schedule with times and forced choice options, use of coping skill training, a feelings thermometer, and communication supports. These interventions had moderate intermittent success; however, overeating and consequent power struggles continued to be the major challenge reported by the family.He was started on a long-acting stimulant medication daily, intended to address impulsive and aggressive behaviors, and with potential benefit of appetite reduction. However, although there were some improvements in behavior, there was little to no effect noted on his appetite. Of note, he was diagnosed with celiac disease and severe obstructive sleep apnea

TÍTULO / TITLE:   - Psychometric evaluation of a working memory assessment measure in young children with Down syndrome

REVISTA / JOURNAL:    - Res Dev Disabil. 2023 Aug;139:104564. doi: 10.1016/j.ridd.2023.104564. Epub 2023 Jul 13.

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AUTORES / AUTHORS: - Miranda E Pinks

INSTITUCIÓN / INSTITUTION: - Human Development and Family Studies, Colorado State University, Fort Collins, CO, United States. 

RESUMEN / SUMMARY: - Background: Working memory involves the temporary storage and manipulation of information and is frequently an area of challenge for individuals with Down syndrome (DS). Despite the potential benefits of intervention, laboratory assessments of working memory that could capture intervention effects have not undergone rigorous evaluation for use with young children with DS. It is critical to evaluate assessments of working memory in young children with DS to ensure the reliable and accurate measurement of performance. Aim: This study evaluated an adapted laboratory measure of working memory for young children with DS 2-8 years old. Method: A self-ordered pointing task, the Garage Game, was administered to 78 children with DS (mean = 5.17 years; SD = 1.49). Adaptations were made to the task to minimize potential DS phenotype-related language and motor confounds. Results: Results indicate that the measure is feasible, scalable, and developmentally sensitive, with minimal floor and practice effects for this population within this chronological and developmental age range. Conclusion: These findings demonstrate that the Garage Game is promising for use in studies of early working memory and treatment trials that aim to support the development of this critical dimension of executive functioning for children with DS.

TÍTULO / TITLE:   - Visuospatial perspective taking in people with Down syndrome

REVISTA / JOURNAL:    - Res Dev Disabil. 2023 Aug;139:104565. doi: 10.1016/j.ridd.2023.104565. Epub 2023 Jul 13.

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AUTORES / AUTHORS: - Arielle Hershkovich et al

INSTITUCIÓN / INSTITUTION: - Montclair State University, USA 

RESUMEN / SUMMARY: - Visuospatial perspective taking (VPT) refers to the process of mentally representing a viewpoint different from ones own. It is related to mental rotation and theory of mind and helps to support some complex spatial activities such as wayfinding. Despite research advances in spatial cognition, little is known about VPT in people with Down syndrome (DS). Here, we examined VPT in people with DS. A total of 38 individuals with DS (aged 12-25 years old) and nonverbal ability-matched typically developing (TD) children (aged 4-9 years old) participated. They completed two VPT tasks: the classic Piagetian Three Mountains Task and a modified version of the "Dog Task" (Newcombe & Huttenlocher, 1992). For both groups, the Three Mountains Task was more difficult than the Dog Task, implying the impact of task complexity on assessing VPT. However, the overall performance did not differ between the TD and DS groups in either VPT task. Implications of the results were discussed.

TÍTULO / TITLE:   - A biophysiological framework exploring factors affecting speech and swallowing in clinical populations: focus on individuals with Down syndrome

REVISTA / JOURNAL:    - Front Psychol. 2023 Jun 21;14:1085779. doi: 10.3389/fpsyg.2023.1085779. eCollection 2023.

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AUTORES / AUTHORS: - Aarthi Madhavan et al

INSTITUCIÓN / INSTITUTION: - Department of Communication Sciences and Disorders, The Pennsylvania State University, University Park, PA, United States. 

RESUMEN / SUMMARY: - Speech and swallowing are complex sensorimotor behaviors accomplished using shared vocal tract anatomy. Efficient swallowing and accurate speech require a coordinated interplay between multiple streams of sensory feedback and skilled motor behaviors. Due to the shared anatomy, speech and swallowing are often both impacted in individuals with various neurogenic and developmental diseases, disorders, or injuries. In this review paper, we present an integrated biophysiological framework for modeling how sensory and motor changes alter functional oropharyngeal behaviors of speech and swallowing, as well as the potential downstream effects to the related areas of language and literacy. We discuss this framework with specific reference to individuals with Down syndrome (DS). Individuals with DS experience known craniofacial anomalies that impact their oropharyngeal somatosensation and skilled motor output for functional oral-pharyngeal activities such as speech and swallowing. Given the increased risk of dysphagia and "silent" aspiration in individuals with DS, it is likely somatosensory deficits are present as well. The purpose of this paper is to review the functional impact of structural and sensory alterations on skilled orofacial behaviors in DS as well as related skills in language and literacy development. We briefly discuss how the basis of this framework can be used to direct future research studies in swallowing, speech, and language and be applied to other clinical populations.

TÍTULO / TITLE:   - Sleep and behavioral problems in Down syndrome: differences between school age and adolescence

REVISTA / JOURNAL:    - Front Psychiatry. 2023 Jun 9;14:1193176. doi: 10.3389/fpsyt.2023.1193176. eCollection 2023.

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AUTORES / AUTHORS: - Elisa Fuca et al

INSTITUCIÓN / INSTITUTION: - Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Childrens Hospital, IRCCS, Rome, Italy 

RESUMEN / SUMMARY: - Background: Individuals with Down syndrome (DS) are at risk of developing sleep problems. In spite of the well-established knowledge on the presence of sleep difficulties in DS individuals and the associated emotional and behavioral problems, less is known about the possible differences in the kind of associations between sleep and emotional/behavioral problems across different age ranges. Methods: In this retrospective study, we included 289 participants with DS aged 6-18 years with the aims to explore differences in the distribution of sleep problems between specific age groups (school age vs. adolescence) and to identify specific age-based associations between sleep problems and emotional/behavioral problems. Results: Some differences in the distribution of sleep problems have emerged between age groups. Moreover, differences in the patterns of association between emotional/behavioral difficulties and sleep problems-in particular, sleep-related breathing difficulties and parasomnias-have been observed. However, sleep-wake transition disorders and excessive daily somnolence appear to be related to emotional and behavioral problems (both internalizing and externalizing), in general, across school age and adolescence. Discussion: These results remark the importance of appropriate neuropsychiatric and psychological evaluation taking into account the age-specific needs and features of individuals with DS

TÍTULO / TITLE:   - Expressive language sampling and outcome measures for treatment trials in fragile X and down syndromes: composite scores and psychometric properties

REVISTA / JOURNAL:    - Sci Rep. 2023 Jun 7;13(1):9267. doi: 10.1038/s41598-023-36087-3.

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AUTORES / AUTHORS: - Leonard Abbeduto et al

INSTITUCIÓN / INSTITUTION: - MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis Health, 2828 50Th St., Sacramento, CA, 95817, USA 

RESUMEN / SUMMARY: - The lack of psychometrically sound outcome measures has been a barrier to evaluating the efficacy of treatments proposed for core symptoms of intellectual disability (ID). Research on Expressive Language Sampling (ELS) procedures suggest it is a promising approach to measuring treatment efficacy. ELS entails collecting samples of a participants talk in interactions with an examiner that are naturalistic but sufficiently structured to ensure consistency and limit examiner effects on the language produced. In this study, we extended previous research on ELS by analyzing an existing dataset to determine whether psychometrically adequate composite scores reflecting multiple dimensions of language can be derived from ELS procedures administered to 6- to 23-year-olds with fragile X syndrome (n = 80) or Down syndrome (n = 78). Data came from ELS conversation and narration procedures administered twice in a 4-week test-retest interval. We found that several composites emerged from variables indexing syntax, vocabulary, planning processes, speech articulation, and talkativeness, although there were some differences in the composites for the two syndromes. Evidence of strong test-retest reliability and construct validity of two of three composites were obtained for each syndrome. Situations in which the composite scores would be useful in evaluating treatment efficacy are outlined

Quality of life - Calidad de vida

TÍTULO / TITLE:   - Personal social networks of people with Down syndrome

REVISTA / JOURNAL:    - Am J Med Genet A. 2023 Mar;191(3):690-698. doi: 10.1002/ajmg.a.63059. Epub 2022 Nov 27.

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AUTORES / AUTHORS: - Brian G Skotko et al.

INSTITUCIÓN / INSTITUTION: - Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA 

RESUMEN / SUMMARY: - Studies in the neurotypical population have demonstrated that personal social networks can mitigate cognitive decline and the development of Alzheimer disease. To assess whether these benefits can also be extended to people with Down syndrome (DS), we studied whether and how personal networks can be measured in this population. We adapted a personal networks instrument previously created, validated, and implemented for the neurotypical population. We created two versions of the survey: one for participants with DS, ages 25 and older, and another for their study partners, who spent a minimum of 10 h/wk in a caregiver role. Participants with DS gave concordant data to those of study partners. Their personal networks included a median network size of 7.50, density 0.80, constraint 46.00, and effective size 3.07. Personal networks were composed of 50% kin, 80% who live within 15 miles, and 80% who eat a healthy diet. In this proof-of-principle study, we demonstrated that the personal networks of people with DS can be quantitatively analyzed, with no statistical difference between self-report and parent-proxy report. Future research efforts can now evaluate interventions to enhance personal networks for preventing Alzheimer disease in this population.

TÍTULO / TITLE:   - Burden of Care among Mothers Having Children with Down Syndrome

REVISTA / JOURNAL:    - J Nepal Health Res Counc. 2023 Jul 20;20(4):977-982. doi: 10.33314/jnhrc.v20i4.4415.

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AUTORES / AUTHORS: - Tulashi Adhikari Mishra et al

INSTITUCIÓN / INSTITUTION: - Maharajgunj Nursing Campus, Institute of Medicine, Tribhuvan University, Kathmandu Nepal. 

RESUMEN / SUMMARY: - Background: Down syndrome is the most common chromosomal disorder associated with mental retardation. Parents who are the primary caregivers of a child with a disability face numerous challenges in their day-to-day life. The objective of the study was to find out the burden of care among mothers having children with down syndrome. Methods: A descriptive cross-sectional study was carried out among 96 mothers having down syndrome children enrolled in the Down Syndrome Society, Nepal. Purposive Sampling technique was adopted for data collection. The Modified Caregiver Strain Index tool was used to collect data through interview. Data were collected from June 14, 2021 to August 1, 2021, which was analyzed by using descriptive and inferential statistics. Results: Findings revealed that majority of the mothers (77.1%) had high level of burden of care. Majority (89.6%) of the mothers involved in the study were always overwhelmed about their childs conditions. More than half (55.2%) of the mothers were always financially strained in care giving, 57.3% had always done work adjustments and 60.4% of mothers always had emotional adjustments to be made. Similarly, 53.1% participants always felt that care giving was a physical strain. Burden of care was significantly associated with the age of delivery (p value= 0.008). Conclusions: The study concludes that mothers having children with Down syndrome tend to have high level of burden of care and it is associated with the age at delivery. Therefore, health care providers including concerned authority are recommended to conduct different programs to support the caregivers in order to reduce their burden as well as to raise awareness program related to preventive measures of Down syndrome in community.

TÍTULO / TITLE:   - Feeding Stressors and Resources Used by Caregivers of Children With Down Syndrome: A Qualitative Analysis

REVISTA / JOURNAL:    - J Acad Nutr Diet. 2023 Jul 8;S2212-2672(23)01207-8. doi: 10.1016/j.jand.2023.07.002.

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AUTORES / AUTHORS: - Caroline Brantley et al

INSTITUCIÓN / INSTITUTION: - Department of Human Nutrition and Hospitality Management, University of Alabama, Tuscaloosa, Alabama. 

RESUMEN / SUMMARY: - Background: Challenging eating behaviors or feeding difficulties, commonly displayed in children with Down syndrome (DS), may amplify perceived stress in caregivers. If caregivers lack resources on how to accommodate the needs of the child with DS, they may find feeding the child stressful and resort to negative coping strategies. Objective: The aim of this study was to understand the feeding stressors, resources, and coping strategies used by caregivers of children with DS. Design: A qualitative analysis of interview transcripts was undertaken, framed around the Transactional Model of Stress and Coping. Participants/setting: Between September to November 2021, 15 caregivers of children (aged 2 through 6 years) with DS, were recruited from 5 states located in the Southeast, Southwest, and West regions of the United States. Analysis: Interviews were audio-recorded, transcribed verbatim, and analyzed using deductive thematic analysis and content analysis approaches. Results: Thirteen caregivers reported increased stress around feeding the child with DS. Stressors identified included concern about adequacy of intake and challenges associated with feeding difficulties. Stress related to feeding was higher among caregivers whose child was learning a new feeding skill or in a transitional phase of feeding. Caregivers used both professional and interpersonal resources in addition to problem- and emotion-based coping strategies. Conclusions: Caregivers identified feeding as a stressful event with higher stress reported during transitional phases of feeding. Caregivers reported that speech, occupational, and physical therapists were beneficial resources to provide support for optimizing nutrition and skill development. These findings suggest that caregiver access to therapists and registered dietitian nutritionists is warranted.

TÍTULO / TITLE:   - Parental perception of facilitators and barriers to health among young children with down syndrome: a qualitative study

REVISTA / JOURNAL:    - Front Pediatr. 2023 Jul 11;11:1155850. doi: 10.3389/fped.2023.1155850. eCollection 2023.

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AUTORES / AUTHORS: - Angela R Caldwell et al

INSTITUCIÓN / INSTITUTION: - Pediatric Health Promotion Laboratory, Department of Occupational Therapy, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA, United States. 

RESUMEN / SUMMARY: - Background: Despite high rates of obesity and weight-related conditions observed in children with Down syndrome, little is known about how to prevent these conditions. Purpose: The purpose of this study was to identify parent-perceived facilitators and barriers to health for toddlers (12-36 months old) with Down syndrome. Materials and methods: We conducted in-depth, semi-structured interviews with the mothers of 25 toddlers with Down syndrome. All interviews were conducted using Zoom Video Technology, audio recorded and transcribed before being coded in NVivo software using a structured protocol. Thematic analysis was used to identify themes in perceived facilitators and barriers to health at the level of the child, family, and community. Data were triangulated using reflective journaling, video review of child meals, and member-checking techniques. Results: We identified unique themes for facilitators (on the move and sound sleep) and barriers (co-occurring conditions and eating behaviors) at the level of the child. At the level of the family and community, overarching themes that were viewed as either a facilitator or barrier, depending on the context, were identified (role models matter, time is critical, the importance of place, and social support). Conclusion: These themes can help clinicians and researchers tailor their health promotion interventions to meet the unique needs of children with Down syndrome by using strength-based approaches and providing families with the tools to overcome barriers.

TÍTULO / TITLE:   - Behavioural adjustment of children with intellectual disability and their sibling is associated with their sibling relationship quality

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2023 Apr;67(4):310-322. doi: 10.1111/jir.13006. Epub 2023 Jan 5.

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AUTORES / AUTHORS: - N K Hayden et al

INSTITUCIÓN / INSTITUTION: - Centre for Educational Development, Appraisal and Research, University of Warwick, Coventry, UK 

RESUMEN / SUMMARY: - Background: Understanding sibling relationship quality is important, as it is associated with mental health outcomes in both childhood and adulthood. Arguably, these relationships are even more important for individuals with intellectual disability, as siblings can be important sources of care, support, advocacy and friendship for one another. The intellectual disability field, however, has a tendency to assume that the relationship lacks reciprocity, and that it is the sibling with intellectual disability who affects the sibling, and that this effect is somehow negative. Methods: We examined whether the behaviour problems and prosocial behaviour of 500 child sibling pairs, where one child has an intellectual disability, were associated with their sibling relationship quality. Measures included the Strengths and Difficulties Questionnaires and the Sibling Relationship Questionnaire. Family poverty, the gender of both children, birth order and whether the child with intellectual disability had autism or Down syndrome were also included in the analyses. Results: Confirmatory factor analysis indicated an adequate model fit for the latent variables measuring sibling relationships. The final structural model found that the prosocial behaviour and internalising problems of the children with intellectual disability, their typically developing siblings prosocial behaviours and sibling birth order were associated with intimacy-companionship in the sibling relationship. The internalising, externalising and prosocial behaviours of the children with intellectual disability, their siblings externalising behaviours and sibling birth order were associated with antagonism-quarrelling in the sibling relationship. Conclusions: We found that the behaviours of both the child with intellectual disability and their sibling were associated with both positive and negative dimensions of their sibling relationship. This indicates a bidirectional and reciprocal effect.

TÍTULO / TITLE:   - Group Changes in Cortisol and Heart Rate Variability of Children with Down Syndrome and Children with Autism Spectrum Disorder during Dog-Assisted Therapy

REVISTA / JOURNAL:    - Children (Basel). 2023 Jul 11;10(7):1200. doi: 10.3390/children10071200.

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AUTORES / AUTHORS: - Richard E Griffioen et al

INSTITUCIÓN / INSTITUTION: - Department of Animal Assisted Interventions, Aeres University of Applied Sciences, De Drieslag 4, 8251 JZ Dronten, The Netherlands 

RESUMEN / SUMMARY: - Dog-assisted therapy is hypothesized to lower stress in children with autism spectrum disorder (ASD) and children with Down syndrome (DS), which may be visible on a physiological level. In this study, we measured heart rate variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of six weekly sessions of dog-assisted therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after six sessions (six weeks). The effect of dog-assisted therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

TÍTULO / TITLE:   - Analysis of Heart Rate, Perception of Physical Effort and Performance of Individuals with Down Syndrome Submitted to a Protocol of Virtual Games for Home-Based Telerehabilitation

REVISTA / JOURNAL:    - Healthcare (Basel). 2023 Jun 30;11(13):1894. doi: 10.3390/healthcare11131894.

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AUTORES / AUTHORS: - Renata Martins Rosa et al

INSTITUCIÓN / INSTITUTION: - Postgraduate Program in Rehabilitation Sciences, Faculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 01246-903, SP, Brazil 

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetic condition associated with impairments in several body systems, which may negatively influence the habit of practicing physical activities (PAs), increasing sedentary habits and the risk of comorbidities. Additionally, difficulty in accessing services, financial limitations and lack of interest may interfere with the practice of PAs. Considering the necessity of developing effective treatment alternatives, to increase the possibility of access and the interest of participants, we conducted a study using telerehabilitation with a virtual task to promote PA and analyze the motor performance of DS individuals. Our protocol consisted of 11 sessions of the virtual game called MoveHero. A total of 34 individuals with DS and 34 individuals with typical development participated in the study. Heart rate (HR) and rating of perceived effort (RPE) were collected at rest and during the game. Our results show that virtual reality presents a great possibility to promote PA and a way out of a sedentary lifestyle for DS individuals, considering the enhancement in HR and RPE found during the protocol for both groups. Moreover, our results show positive outcomes regarding motor performance, with significant improvement in the task with practice, demonstrating that individuals with DS are able to improve their motor proficiency with adequate stimuli in the virtual environment.

TÍTULO / TITLE:   - Parents Experiences of Having a Child with Down Syndrome and Sleep Difficulties

REVISTA / JOURNAL:    - Behav Sleep Med. 2023 Sep 3;21(5):570-584. doi: 10.1080/15402002.2022.2143359. Epub 2022 Nov 11.

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AUTORES / AUTHORS: - Jasneek K Chawla et al

INSTITUCIÓN / INSTITUTION: - Department of Paediatric Respiratory & Sleep Medicine, Queensland Childrens Hospital, Brisbane, Australia. 

RESUMEN / SUMMARY: - Objectives: Sleep disorders are prevalent in children with Down Syndrome (DS). However, sleep treatment is not always readily accessed by this group. This study aims to understand families experiences of having a child with DS and sleep difficulties, and in particular, their healthcare experiences, with the goal of informing practice improvements. Methods: We conducted semi-structured interviews with 34 parents (fathers n = 4 and mothers n = 30) with open-ended questions about parents experiences of sleep, family dynamics, and healthcare. We operationalized a reflexive Thematic Analysis. Results: Parents normalized their experiences of having a child with DS and sleep problems. Parents acknowledged that sleep disruption has adverse and pervasive impacts on their wellbeing and family dynamics, but also found this difficult to identify as a health problem. They accepted sleep difficulties as a regular part of bringing up any child, particularly one with a disability. When they did seek treatment for their childs sleep difficulties, parents often reported encountering insensitive and inadequate care and described that, at times, healthcare professionals also normalized childrens sleep difficulties, resulting in sub-optimal treatment. This included at times failure to refer to tertiary sleep medicine services when required. Conclusions: Parents and healthcare professionals normalization of sleeping difficulties denies that they are both deleterious and modifiable. Practice implications include raising healthcare professionals awareness of the importance of proactively addressing sleep, with sensitivity to families normalization strategies, recognizing that families may require prompting to report concerns.

Respiratory - Respiratorio

TÍTULO / TITLE:   - Cardiopulmonary Phenotypes and Protein Signatures in Children With Down Syndrome

REVISTA / JOURNAL:    - Clin Pediatr (Phila). 2023 Jun 12;99228231179453. doi: 10.1177/00099228231179453.

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AUTORES / AUTHORS: - Emily M DeBoer et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA 

RESUMEN / SUMMARY: - Pulmonary disease, lower respiratory tract infection, and pneumonia are the largest causes of morbidity and mortality in individuals with Down syndrome (DS), but whether pulmonary diagnoses in children with DS are common and occur independently of cardiac disease and pulmonary hypertension (PH) is unknown. Cardiopulmonary phenotypes were examined in a cohort of 1248 children with DS. Aptamer-based proteomic analysis of blood was performed in a subset (n = 120) of these children. By the age of 10 years, half of the patients in this cohort (n = 634, 50.8%) had co-occurring pulmonary diagnoses. That proteins and related pathways were distinct between children with pulmonary diagnoses and those with cardiac disease and/or PH may indicate that pulmonary diagnoses appear to occur independently of cardiac disease and PH. Heparin sulfate-glycosaminoglycan degradation, nicotinate metabolism, and elastic fiber formation were ranked highest in the group with pulmonary diagnoses.

TÍTULO / TITLE:   - Sleep apnea in people with Down syndrome: Causes and effects of physical activity?

REVISTA / JOURNAL:    - Front Neurol. 2023 Feb 2;14:1123624. doi: 10.3389/fneur.2023.1123624. eCollection 2023

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AUTORES / AUTHORS: - Duy-Thai Nguyen et al.

INSTITUCIÓN / INSTITUTION: - Clinical Research Committee, Vietnam Society of Sleep Medicine (VSSM), Da Lat, Vietnam 

RESUMEN / SUMMARY: - Poor sleep quality is recognized as a major risk factor for poor health, increasing the incidence of serious chronic diseases. In people with Down syndrome, sleep apnea prevalence is significantly greater, it is caused by genetic, anatomical, endocrine, and metabolic abnormalities. The consequences of sleep disruption due to sleep apnea are very serious, especially in terms of neurocognitive and cardiovascular effects, leading to reduced life expectancy and quality of life in this population. However, the management, care, and treatment of related disorders in people with Down syndrome are still inadequate and limited. Therefore, this article wants to increase understanding and awareness about sleep apnea and the benefits of physical activity in improving sleep quality in the Down syndrome community, families, and their care specialists.

TÍTULO / TITLE:   - Incidence and clinical outcomes of pneumonia in persons with Down syndrome in the United States

REVISTA / JOURNAL:    - Vaccine. 2023 Jul 12;41(31):4571-4578. doi: 10.1016/j.vaccine.2023.05.063. Epub 2023 Jun 14

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AUTORES / AUTHORS: - Edward N Janoff et al

INSTITUCIÓN / INSTITUTION: - Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA; Denver Veterans Affairs Medical Center, Aurora, CO, USA.  

RESUMEN / SUMMARY: - Background: Persons with Down syndrome (DS) experience an increased risk of pneumonia. We determined the incidence and outcomes of pneumonia and relationship to underlying comorbidities in persons with and without DS in the United States. Methods: This retrospective matched cohort study used de-identified administrative claims data from Optum. Persons with DS were matched 1:4 to persons without DS on age, sex, and race/ethnicity. Pneumonia episodes were analyzed for incidence, rate ratios and 95 % confidence intervals, clinical outcomes, and comorbidities. Results: During 1-year follow-up among 33796 persons with and 135184 without DS, the incidence of all-cause pneumonia (pneumonia) was substantially higher among people with DS than those without DS (12427 vs. 2531 episodes/100000 person-years; 4.7-5.7 fold increase). Persons with DS and pneumonia were more likely to be hospitalized (39.4 % vs. 13.9 %) or admitted to the ICU (16.8 % vs. 4.8 %). Mortality was higher 1 year after first pneumonia (5.7 % vs. 2.4 %; P < 0.0001). Results were similar for episodes of pneumococcal pneumonia. Specific comorbidities were associated with pneumonia, particularly heart disease in children and neurologic disease in adults, which only partially mediated the effect of DS on pneumonia. Conclusions: Among persons with DS, incidence of pneumonia and associated hospitalizations were increased; mortality among those with pneumonia was comparable at 30 days, but higher at 1 year. DS should be considered an independent risk condition for pneumonia.

TÍTULO / TITLE:   - What are the Soft Tissue Risk Factors for Obstructive Sleep Apnea in Patients with Downs Syndrome?

REVISTA / JOURNAL:    - Cleft Palate Craniofac J. 2023 Aug;60(8):986-992. doi: 10.1177/10556656221088171. Epub 2022 Mar 21.

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AUTORES / AUTHORS: - Dani Stanbouly et al

INSTITUCIÓN / INSTITUTION: - Columbia University College of Dental Medicine, New York, NY, USA. 

RESUMEN / SUMMARY: - Objective: To determine the risk factors and their respective magnitudes for developing Obstructive Sleep Apnea (OSA) in Down syndrome (DS) patients. Design: Retrospective cohort study. Patients: The 2016 Kids Inpatient Database (KID) was queried to identify all patients diagnosed with DS. Main outcome measures: The primary predictor variables were tonsillar hypertrophy (TH), adenoidal hypertrophy (AH), Hypertrophy of Tonsils & Adenoids (HTA), Laryngeal Stenosis (LS), Hypotonia, Glossoptosis, Congenital Laryngomalacia (CL), and Overweight & Obesity (OO). The primary outcome variable was OSA. Results: The final sample consisted of 18,181 patients with a diagnosis of DS. Relative to patients aged 0-5, patients aged 6-10 (OR 3.5, P < 0.01), 11-5 (OR 3.4, P < 0.01), and 16 & above (OR 3.6, P < 0.01) were each independently associated with increased odds of OSA. Further, TH (OR 23.2, P < 0.01), AH (OR 20.3, P < 0.01), HTA (OR 64.2, P < 0.01), glossoptosis (OR 5.0, P < 0.01), CL (OR 4.3, P < 0.01), and OO (OR 3.7, P < 0.01) were all independent risk factors for OSA. Conclusions: The presence of hypertrophied tonsils and adenoids together was the strongest risk factor for OSA. DS patients aged six and above were at risk for OSA development relative to younger patients. Patients with DS should be tested for OSA, which otherwise will deteriorate their existing comorbidities.

TÍTULO / TITLE:   - Obstructive sleep apnea in children with Down syndrome: contribution of upper airway and chemosensitivity

REVISTA / JOURNAL:    - Pediatr Res. 2023 Jul 10. doi: 10.1038/s41390-023-02718-8.

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AUTORES / AUTHORS: - Plamen Bokov et al.

INSTITUCIÓN / INSTITUTION: - Universite de Paris-Cite, AP-HP, Hopital Robert Debre, Service de Physiologie Pediatrique-Centre du Sommeil, INSERM NeuroDiderot, F-75019, Paris, France.  

RESUMEN / SUMMARY: - Background: The high prevalence of obstructive sleep apnea syndrome (OSAS) in children with Down syndrome (DS) has been attributed to a reduced upper airway size, while the role of ventilatory control is unclear. The objectives of our case-control study were to evaluate the upper airway reduction in children with DS and moderate to severe OSAS as compared to typically developing (TD) children with similar OSAS severity and to evaluate the degree of chemical loop gain modifications including its components: controller and plant gains (CG, PG). Methods: Thirteen children with DS were matched for age, sex, OSAS severity and ethnicity with 26 TD children. They had undergone acoustic rhinometry and pharyngometry, chemical LG obtained during awake tidal breathing measurement and hypercapnic-hyperoxic ventilatory response testing. Results: As compared to TD, children with DS depicted reduced oropharyngeal dimensions, significantly lower CG and LG and no different PG. Their hypercapnic ventilatory response slopes were not different. Conclusions: We concluded that the decreased CG in DS was related to decreased peripheral chemoreceptor sensitivity, and while central chemosensitivity was normal, the former explained the increased end-tidal PCO2 observed in children with DS as compared to TD. Pharyngeal dimensions are reduced in children with DS and OSAS. Impact: Reduced upper airway size and nocturnal alveolar hypoventilation in children with Down syndrome (DS) have been previously reported. We confirmed that children with DS and moderate-to-severe OSA have reduced oropharyngeal size as compared to typically developing children with similar OSAS severity and demonstrated decreased peripheral chemosensitivity explaining the alveolar hypoventilation observed in children with DS. Central chemosensitivity appears to be intact in children with DS and moderate to severe OSAS Our results support growing evidence that Down syndrome is associated with autonomic nervous system dysfunct

TÍTULO / TITLE:   - Sleep assessment in adults with Down syndrome: correlation between functionality and polysomnographic findings

REVISTA / JOURNAL:    - Arq Neuropsiquiatr. 2023 Jun;81(6):544-550. doi: 10.1055/s-0043-1768670. Epub 2023 Jun 28.

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AUTORES / AUTHORS: - Marilia Rezende Callegari et al

INSTITUCIÓN / INSTITUTION: - Universidade Presbiteriana Mackenzie, Centro de Ciencias Biologicas e da Saude, Sao Paulo SP, Brazil 

RESUMEN / SUMMARY: - in English, Portuguese. Background: Sleep disorders have a negative impact on health, being associated with neurocognitive problems, cardiovascular diseases and obesity, influencing childrens development and learning. Objective: To assess the sleep pattern of people with Down syndrome (DS) and correlate changes with functionality and behavior. Methods: A cross-sectional study was conducted to evaluate the sleep pattern in adults with DS > 18 years old. Twenty-two participants were assessed using the Pittsburgh Sleep Quality Index, the Functional Independence Measure and the Strengths and Difficulties Questionnaire, and the 11 who presented indications of disorders by the screening questionnaires were referred to polysomnography. Statistical tests were performed using a significance level of 5%, including sample normality tests and correlation tests (sleep and functionality). Results: Impairment in sleep architecture was found due to an increase in the rate of awakenings in 100% of the participants, a decrease in the number of slow waves, and a high prevalence of sleep disordered breathing (SDB), with higher averages in the Apnea and Hypopnea Index (AHI) in the group. There was a negative correlation between sleep quality and global functionality (p = 0.011) and the motor (p = 0.074), cognitive (p = 0.010), and personal care (p = 0.072) dimensions in the group. Global and hyperactivity behavior changes were related to worse sleep quality (p = 0.072; p = 0.015, respectively). Conclusion: There is an impairment in the sleep quality of adults with DS, with an increase in the rate of awakenings, a decrease in the number of slow waves, and a high prevalence of SDB affecting this population in the functional and behavioral aspects.

TÍTULO / TITLE:   - Contactless sleep monitoring using the Sonomat in children with Down syndrome

REVISTA / JOURNAL:    - Sleep Med. 2023 Jun 28;109:104-109. doi: 10.1016/j.sleep.2023.06.028.

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AUTORES / AUTHORS: - A J Collaro et al

INSTITUCIÓN / INSTITUTION: - Child Health Research Centre, The University of Queensland, Australia; Department of Respiratory and Sleep Medicine, Queensland Childrens Hospital, Australia. 

RESUMEN / SUMMARY: - Background: Children with Down syndrome (DS) require multiple sleep studies throughout childhood to diagnose and monitor sleep disordered breathing (SDB). Previous research suggests sensors applied during polysomnography (PSG) are poorly tolerated by children with DS. The Sonomat is a contactless device previously validated in typically developing children, and adult populations. Our study aimed to compare simultaneous Sonomat and PSG recordings in children with DS to determine the suitability of the Sonomat for use in this population. Methods: Fifty children with DS undergoing diagnostic PSG were recruited from the Queensland Childrens Hospital sleep laboratory. Agreement for sleep and respiratory parameters were assessed using concordance correlation coefficients (CCC), while detection and classification of SDB were assessed using indicators such as sensitivity, specificity, likelihood ratios, and receiver operator characteristic curves. Results: Comparison of parameters including the apnea-hypopnea index (CCC=89%; 95%CI 76, 93), and obstructive events index (CCC=74%; 95%CI 44, 88) showed reasonable agreement between Sonomat and PSG. The Sonomat showed outstanding ability to differentiate between the presence and absence of SDB (area under the curve [AUC]=0.97; 95%CI 0.93, 1.00), though we are uncertain of its ability to classify SDB profile and severity due to sample size limitations resulting in wide confidence intervals. Conclusions: The easy-to-use, non-invasive nature of the Sonomat make it ideal for use in the screening of SDB in children with DS. Further data are needed to determine its suitability for classifying SDB profile and severity, including within the home, and for its use in other neurodevelopmental groups.

TÍTULO / TITLE:   - The management of residual OSA post-adenotonsillectomy in children with Down syndrome: The experience of a large tertiary sleep service

REVISTA / JOURNAL:    - Sleep Med. 2023 Jun 20;109:158-163. doi: 10.1016/j.sleep.2023.06.009.

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AUTORES / AUTHORS: - Sarah Tanner et al

INSTITUCIÓN / INSTITUTION: - Child Health Research Centre, Faculty of Medicine, The University of Queensland, Australia.  

RESUMEN / SUMMARY: - Introduction: Obstructive Sleep Apnoea (OSA) is common in children with Down Syndrome (DS). Adenotonsillectomy is regarded as first line treatment for OSA but does not always lead to resolution of symptoms in this group of children. Management of residual OSA is variable with no existing recommendations to guide clinical practice. Aim: To describe the experience of a large tertiary sleep service in managing residual OSA in children with DS following upper airway surgery (adenotonsillectomy, adenoidectomy or tonsillectomy). Methods: A retrospective study of children who were under evaluation at the Queensland Childrens Hospital sleep medicine department between October 2013 to April 2022 for residual OSA, after upper airway surgery was undertaken. Results: 148 children with DS who underwent polysomnography for evaluation of OSA were identified. 100 were included in this study and of these, 77 underwent adenotonsillectomy, 19 adenoidectomy, and 4 tonsillectomy. Post-surgical PSG data of all 100 children showed residual mixed sleep disordered breathing in 68 children. 41 were recommended CPAP following surgery, while 21 underwent further surgery. Conclusions: Residual OSA was confirmed to be highly prevalent in children with DS who had already undergone upper airway surgery for OSA. This study identified that CPAP is possible to establish in most children with DS and can be used to manage residual OSA in this population. Approximately one-third of this group were able to discontinue therapy at a median duration of 18 months, suggesting resolution of disease with time can occur in some children.

TÍTULO / TITLE:   - Prediction of obstructive sleep apnoea in children and adolescents with Down syndrome

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2023 Jun 29. doi: 10.1111/jir.13065.

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AUTORES / AUTHORS: - P R Wijayaratne et al

INSTITUCIÓN / INSTITUTION: - Department of Paediatrics, Monash University, Melbourne, Victoria, Australia 

RESUMEN / SUMMARY: - Background: Obstructive sleep apnoea (OSA) is common in children and adolescents with Down syndrome (DS). Clinical guidelines recommend that all children with DS have polysomnography (PSG) for assessment of OSA by the age of 4 years, but access is limited and testing may be burdensome for children and families. Methods: The purpose of this prospective cross-sectional cohort study was to identify a model to predict OSA in this group that could be tested in an external population to triage children and adolescents with DS for PSG. These models were based on a comprehensive set of potential predictive demographic, anthropometric, quality of life and sleep-related variables. Results: The results of this study show the predictive power of a model based on the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in determining moderate-severe OSA in children and adolescents with DS. This model exhibits high sensitivity (82%), specificity (80%), positive predictive value (75%) and negative predictive value (86%). Conclusions: We demonstrate the utility of a tool containing the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in identifying children and adolescents with DS who have moderate/severe OSA.

TÍTULO / TITLE:   - Follow-up of children with Down syndrome and sleep disordered breathing and the effects of treatment on actigraphically recorded sleep, quality of life, behaviour, and daytime functioning

REVISTA / JOURNAL:    - J Sleep Res. 2023 Jun 21;e13970. doi: 10.1111/jsr.13970.

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AUTORES / AUTHORS: - Rosemary S C Horne et al.

INSTITUCIÓN / INSTITUTION: - Department of Paediatrics, Monash University, Melbourne, Victoria, Australia. 

RESUMEN / SUMMARY: - Children with Down syndrome are at increased risk of obstructive sleep disordered breathing, which has deleterious effects on daytime functioning. We aimed to examine the effects of treatment of sleep disordered breathing on sleep quality and daytime functioning in children with Down syndrome, and hypothesised that these would be improved. Thirty-four children completed a baseline study and a follow-up 2 years later. Measures at both time points included 7 days of actigraphy and parents completed a number of questionnaires assessing sleep, behaviour, daytime functioning, and quality of life. All children had overnight polysomnography at baseline; 15 children (44%) were treated. At baseline the treated group had more severe sleep disordered breathing compared with the untreated group: obstructive apneoa-hypopnoea index 29.3 ± 38.2 events/h versus 3.3 ± 5.2 events/h (p < 0.01). Actigraphy showed no significant differences in total sleep time, sleep efficiency, sleep schedules from baseline to follow up in either group. The sleep disturbance (p < 0.01) and total problems (p < 0.05) scales on the OSA-18 and the sleep disordered breathing subscale on the Paediatric Sleep Problem Survey Instrument (p < 0.01) improved in the treated children. There were no changes in any measure in the untreated children. Treatment of sleep disordered breathing improves symptoms, sleep disturbance and quality of life in children with Down syndrome, but has no demonstrable impact on actigraphic sleep measures or daytime behaviour or function. In contrast, children who were not treated, despite having less severe disease at baseline, had increased sleep disruption and no change in quality of life.

TÍTULO / TITLE:   - Dysphagia severity is associated with worse sleep-disordered breathing in infants with Down syndrome

REVISTA / JOURNAL:    - J Clin Sleep Med. 2023 May 1;19(5):883-887. doi: 10.5664/jcsm.10446.

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AUTORES / AUTHORS: - Yeilim Cho et al

INSTITUCIÓN / INSTITUTION: - Sleep Center, University of Washington, Seattle, Washington 

RESUMEN / SUMMARY: - Study objectives: Hypotonia, commonly seen in infants with Down syndrome (I-DS), can contribute to masticatory and oropharyngeal muscle weakness, increasing the risk for dysphagia and sleep-disordered breathing. Data describing the occurrence of dysphagia and sleep-disordered breathing in I-DS are limited. This study aims to determine the frequency and severity of dysphagia and its relationship to polysomnogram parameters in I-DS. Methods: We included I-DS who underwent polysomnography at a single academic center over a 6-year period. Data collected included sex, age, presence of dysphagia (low suspicion of dysphagia vs dysphagia vs feeding tube), and polysomnographic data. Dysphagia was determined by a video fluoroscopic swallow study in the presence of clinical suspicion. Results: A total of 40 I-DS were identified (mean age 6.6 months ± 3; male 65%). There were 11, 13, and 16 I-DS with low suspicion of dysphagia, dysphagia, and feeding tube, respectively. Obstructive sleep apnea was more severe in I-DS in the feeding tube group when compared with the group with a low suspicion of dysphagia and (apnea-hypopnea index mean [standard error] = 49.3 [7.6] vs 19.2 [9.2] events/h; P = .016). Dysphagia severity was positively correlated with a higher obstructive apnea-hypopnea index (r = .43, P = .006). Conclusions: There is a high incidence of dysphagia and sleep-disordered breathing in I-DS. Dysphagia severity correlated with obstructive apnea-hypopnea index severity. Our results suggest that I-DS need early evaluation of both sleep-disordered breathing and dysphagia.

TÍTULO / TITLE:   - How to study sleep apneas in mouse models of human pathology

REVISTA / JOURNAL:    - J Neurosci Methods. 2023 Jul 15;395:109923. doi: 10.1016/j.jneumeth.2023.109923. Epub 2023 Jul 17.

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AUTORES / AUTHORS: - Sara Alvente et al

INSTITUCIÓN / INSTITUTION: - PRISM Lab, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy 

RESUMEN / SUMMARY: - Sleep apnea, the most widespread sleep-related breathing disorder (SBD), consists of recurrent episodes of breathing cessation during sleep. This condition can be classified as either central (CSA) or obstructive (OSA) sleep apnea, with the latest being the most common and toxic. Due to the complexity of living organisms, animal models and, particularly, mice still represent an essential tool for the study of SBD. In the present review we first discuss the methodological pros and cons in the use of whole-body plethysmography to coupling respiratory and sleep measurements and to characterize CSA and OSA in mice; then, we draw an updated and objective picture of the methods used so far in the study of sleep apnea in mice. Most of the studies present in the literature used intermittent hypoxia to mimic OSA in mice and to investigate consequent pathological correlates. On the contrary, few studies using genetic manipulation or high-fat diets investigated the pathogenesis or potential treatments of sleep apnea. To date, mice lacking orexins, hemeoxygenase-2, monoamine oxidase A, Phox2b or Cdkl5 can be considered validated mouse models of sleep apnea. Moreover, genetically- or diet-induced obese mice, and mice recapitulating Down syndrome were proposed as OSA models. In conclusion, our review shows that despite the growing interest in the field and the need of new therapeutical approaches, technical complexity and inter-study variability strongly limit the availability of validated mouse of sleep apnea, which are essential in biomedical research.

Therapeutics - Terapéutica

TÍTULO / TITLE:   - RNA Therapeutics: A Healthcare Paradigm Shift

REVISTA / JOURNAL:    - Biomedicines. 2023 Apr 25;11(5):1275. doi: 10.3390/biomedicines11051275

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AUTORES / AUTHORS: - Sarfaraz K Niazi

INSTITUCIÓN / INSTITUTION: - College of Pharmacy, University of Illinois, Chicago, IL 60612, USA. 

RESUMEN / SUMMARY: - COVID-19 brought about the mRNA vaccine and a paradigm shift to a new mode of treating and preventing diseases. Synthetic RNA products are a low-cost solution based on a novel method of using nucleosides to act as an innate medicine factory with unlimited therapeutic possibilities. In addition to the common perception of vaccines preventing infections, the newer applications of RNA therapies include preventing autoimmune disorders, such as diabetes, Parkinsons disease, Alzheimers disease, and Down syndrome; now, we can deliver monoclonal antibodies, hormones, cytokines, and other complex proteins, reducing the manufacturing hurdles associated with these products. Newer PCR technology removes the need for the bacterial expression of DNA, making mRNA a truly synthetic product. AI-driven product design expands the applications of mRNA technology to repurpose therapeutic proteins and test their safety and efficacy quickly. As the industry focuses on mRNA, many novel opportunities will arise, as hundreds of products under development will bring new perspectives based on this significant paradigm shift-finding newer solutions to existing challenges in healthcare.

TÍTULO / TITLE:   - Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome

REVISTA / JOURNAL:    - Adv Mater. 2023 Jun 5;e2211241. doi: 10.1002/adma.202211241.

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AUTORES / AUTHORS: - Paul J Derry et al

INSTITUCIÓN / INSTITUTION: - Center for Genomic and Precision Medicine, Department of Translational Medical Science, Institute of Bioscience and Technology, Texas A&M Health Science Center, 2121 W. Holcombe Boulevard, Houston, Texas, USA. 

RESUMEN / SUMMARY: - Hydrogen sulfide (H2 S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2 S is elevated and associated with degraded mitochondrial function. Therefore, removing H2 S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2 S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2 S) to polysulfides (HS2+n - ) and thiosulfate (S2 O3 2- ) by poly(ethylene glycol) hydrophilic carbon clusters (PEG-HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG-OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2 S to polysulfides and S2 O3 2- in a dose-dependent manner. The reaction is dependent on O2 and the presence of quinone groups on the OCNs. In DS donor lymphocytes we found that OCNs increased polysulfide production, proliferation, and afforded protection against additional toxic levels of H2 S compared to untreated DS lymphocytes. Finally, in Dp16 and Ts65DN murine models of DS, we found that OCNs restored osteoclast differentiation. This new action suggests potential facile translation into the clinic for conditions involving excess H2 S exemplified by DS.

Urinary/Renal - Urinario/Renal

TÍTULO / TITLE:   - Posterior urethral valves in patients with trisomy 21: Similar renal outcomes and rates of volitional voiding

REVISTA / JOURNAL:    - J Pediatr Urol. 2023 Apr 26;S1477-5131(23)00130-4. doi: 10.1016/j.jpurol.2023.04.002.

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AUTORES / AUTHORS: - Alice Xiang et al

INSTITUCIÓN / INSTITUTION: - Division of Urology, Childrens Hospital of Philadelphia, Philadelphia, PA, USA; Department of Urology, Einstein Healthcare Network, Philadelphia, PA, USA. 

RESUMEN / SUMMARY: - Introduction: Posterior urethral valves (PUV) occur in patients with Down Syndrome (DS) at a rate of 3-4%; far higher than the general population. Our understanding of the relationship between PUVs and DS is in its infancy, with the majority of the literature consisting of case reports. In this study, we present the largest known series of DS patients with PUVs. Aim: We hypothesized that patients with DS and PUVs would have worse functional bladder outcomes and renal outcomes when compared to PUV patients without DS. Study design: We queried our prospectively managed multi-institutional database of PUV patients from 1990 to 2021. We identified patients with a concomitant diagnosis of DS and PUV. In addition, we performed a systematic review of the literature describing the presentation of children with PUV and DS. Patient demographics, renal outcomes, voiding habits, surgical interventions, and radiologic images were aggregated and analyzed. Results: Out of the 537 patients in our PUV database, we identified 18 patients with a concomitant diagnosis of PUV and DS, as well as 14 patients with a concomitant diagnosis of PUV and DS from the literature. DS and non-DS patients had a similar age at presentation, 31.5 days (2-731) and 17 (4-846), and length of follow up 6.32 years (2-11.2) and 6.98 (1-13). Both groups had similar nadir creatinines DS 0.43 (0.4-0.8), non-DS 0.31 (0.2-0.5) and similar rates of renal failure (DS 11.1% and non-DS 14.5%). With respect to bladder outcomes, a similar percentage of patients were volitionally voiding at last follow up (DS 72.2% and non-DS 72.3%). Our literature review corroborated these findings. Conclusions: Patients with DS and PUV have similar renal outcomes to other PUV patients in terms of renal function, progression to renal failure, and probability of volitional voiding with continence. Given the increased rate of PUVs in the DS population, physicians should have a high index of suspicion for PUV when patients with DS presen

Education - Educación

TÍTULO / TITLE:   - Home-literacy environments and language development in toddlers with Down syndrome

REVISTA / JOURNAL:    - Front Psychol. 2023 Jun 29;14:1143369. doi: 10.3389/fpsyg.2023.1143369. eCollection 2023.

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AUTORES / AUTHORS: - Madison S Dulin et al

INSTITUCIÓN / INSTITUTION: - Department of Communication Sciences and Disorders, University of Mississippi, University, MS, United States. 

RESUMEN / SUMMARY: - Introduction: The present study aimed to (1) characterize the home-literacy environments (HLE) of toddlers with Down syndrome (DS) and (2) examine if richness of the HLE, child engagement during shared storybook reading activities, quality of a caregiver-child shared storybook reading activity, and exposure to language in the home environment predicted child receptive vocabulary concurrently (Time 1) and 6 months later (Time 2). Methods: Participants were toddlers with DS (n = 13 at Time 1, 11-29 months of age; n = 10 at Time 2) and their mothers. Mothers completed a Home Literacy Environment Questionnaire at Time 1, which was used to characterize the HLE and to calculate two composite variables: richness of the HLE and child engagement in shared storybook reading. Also at Time 1, the home language environment was measured using adult word count from the LENA Recorder DLP©. The LENA was also used to audio-record and capture the quality of a caregiver-child storybook reading task in the childs home using the book Dear Zoo. At both time points, mothers completed the MacArthur-Bates Communicative Development Inventories, and the number of words understood variable was used to measure receptive vocabulary. Results/discussion: Results indicated that toddlers with DS experience rich HLEs and interactive shared storybook reading encounters with their mothers. A multiple linear regression revealed that child engagement and the home language environment correlated with both toddlers concurrent and later receptive vocabularies, while the richness of the HLE and the shared storybook reading task emerged as moderate predictors of receptive vocabulary 6 months later.

TÍTULO / TITLE:   - Parent-implemented augmented communication intervention and young children with Down syndrome: an exploratory report

REVISTA / JOURNAL:    - Front Psychol. 2023 Jun 13;14:1168599. doi: 10.3389/fpsyg.2023.1168599. eCollection 2023.

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AUTORES / AUTHORS: - MaryAnn Romski

INSTITUCIÓN / INSTITUTION: - 1Departments of Communication and Psychology, Georgia State University, Atlanta, GA, United States 

RESUMEN / SUMMARY: - : Introduction: Young children with Down syndrome (DS) present with speech and language impairments very early in childhood. Historically, early language intervention for children with DS included manual signs, though recently there has been an interest in the use of speech-generating devices (SGDs). This paper examines the language and communication performance of young children with DS who participated in parent-implemented communication interventions that included SGDs. Specifically, we compared the functional vocabulary usage and communication interaction skills of children with DS who received augmented communication interventions (AC) that included an SGD with those children with DS who received spoken communication intervention (SC). Methods: Twenty-nine children with DS participated in this secondary data analysis. These children were part of one of two longitudinal RCT studies investigating the effectiveness of parent-implemented augmented communication interventions in a larger sample of 109 children with severe communication and language impairments. Results: There were significant differences between children with DS in the AC and SC groups in terms of the number and proportion of functional vocabulary targets used and the total vocabulary targets provided during the intervention at sessions 18 (lab)and 24 (home). Discussion: Overall, the AC interventions provided the children with a way to communicate via an SGD with visual-graphic symbols and speech output, while the children in the SC intervention were focused on producing spoken words. The AC interventions did not hinder the childrens spoken vocabulary development. Augmented communication intervention can facilitate the communication abilities of young children with DS as they are emerging spoken communicators.

TÍTULO / TITLE:   - Cognitive-motor interference during standing stance across different postural and cognitive tasks in individuals with Down syndrome

REVISTA / JOURNAL:    - Res Dev Disabil. 2023 Aug;139:104562. doi: 10.1016/j.ridd.2023.104562. Epub 2023 Jun 26.

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AUTORES / AUTHORS: - Rihab Borji et al

INSTITUCIÓN / INSTITUTION: - Research Laboratory: Education, Motricite, Sport et Sante, EM2S, LR19JS01, High Institute of Sport and Physical Education of Sfax, University of Sfax, Sfax, Tunisia. 

RESUMEN / SUMMARY: - Background: Individuals with Down syndrome (DS) presented both cognitive and motor impairments that could influence each other. Therefore, exploring cognitive-motor interference during standing stance is relevant in this population. Aims: This study explored the dual task (DT) effects on postural balance during diverse cognitive tasks and sensory manipulations in individuals with DS, compared to those with typical development (TD). Methods and procedures: Fifteen adolescents with DS (age = 14.26 ± 1.27 years; height = 1.50 ± 0.02; weight = 46.46 ± 4.03 kg; BMI =20.54 ± 1.51 kg/m2) and thirteen with TD (age = 14.07 ± 1.11 years; height = 1.50 ± 0.05; weight = 44.92 ± 4.15 kg; BMI =19.77 ± 0.94 kg/m2) participated in this study. Postural and cognitive performances for the selective span task (SST) and the verbal fluency (VF) were recorded during single task (ST) and DT conditions. Postural conditions were: firm eyes open (firm-EO), firm eyes closed (firm-EC) and foam-EO. Motor and cognitive DT costs (DTC) were calculated and analyzed across these different cognitive and postural conditions. Outcomes and results: In the DS group, postural performance was significantly (p < 0.001) altered during all DT conditions, compared to the ST situation. Moreover, the motor DTC was significantly (p < 0.001) higher while performing the VF task than the SST. However, in the control group, postural performance was significantly (p < 0.001) impaired only while performing the VF test in the DT-Firm EO condition. For both groups, cognitive performances were significantly (p < 0.05) altered in all DT conditions compared to the ST one. Conclusion: Adolescents with DS are more prone to DT effects on postural balance than those with TD.

TÍTULO / TITLE:   - Talkitt: toward a new instrument based on artificial intelligence for augmentative and alternative communication in children with Down syndrome

REVISTA / JOURNAL:    - Front Psychol. 2023 Jun 6;14:1176683. doi: 10.3389/fpsyg.2023.1176683. eCollection 2023.

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AUTORES / AUTHORS: - Floriana Costanzo et al

INSTITUCIÓN / INSTITUTION: - Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Childrens Hospital, IRCCS, Rome, Italy. 

RESUMEN / SUMMARY: - Introduction: Individuals with Down syndrome (DS) often exhibit a severe speech impairment, with important consequences on language intelligibility. For these cases, the use of Augmentative Alternative Communication instruments, that increase an individuals communication abilities, becomes crucial. Talkitt is a mobile application created by Voiceitt Company, exploiting speech recognition technology and artificial intelligence models to translate in real-time unintelligible sounds into clear words, allowing individuals with language production impairment to verbally communicate in real-time. Methods: The study evaluated the usability and satisfaction related to the Talkitt application use, as well as effects on adapted behavior and communication, of participants with DS. A final number of 23 individuals with DS, aged 5.54 to 28.9 years, participated in this study and completed 6 months of training. The application was trained to consistently recognize at least 20 different unintelligible words (e.g., nouns and/or short phrases)/person. Results: Results revealed good usability and high levels of satisfaction related to the application use. Moreover, we registered improvement in linguistic abilities, particularly naming. Discussion: These results paves the road for a potential role of Talkitt application as a supportive and rehabilitative tool for DS.

TÍTULO / TITLE:   - A biophysiological framework exploring factors affecting speech and swallowing in clinical populations: focus on individuals with Down syndrome

REVISTA / JOURNAL:    - Front Psychol. 2023 Jun 21;14:1085779. doi: 10.3389/fpsyg.2023.1085779. eCollection 2023.

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AUTORES / AUTHORS: - Aarthi Madhavan et al

INSTITUCIÓN / INSTITUTION: - Department of Communication Sciences and Disorders, The Pennsylvania State University, University Park, PA, United States 

RESUMEN / SUMMARY: - Speech and swallowing are complex sensorimotor behaviors accomplished using shared vocal tract anatomy. Efficient swallowing and accurate speech require a coordinated interplay between multiple streams of sensory feedback and skilled motor behaviors. Due to the shared anatomy, speech and swallowing are often both impacted in individuals with various neurogenic and developmental diseases, disorders, or injuries. In this review paper, we present an integrated biophysiological framework for modeling how sensory and motor changes alter functional oropharyngeal behaviors of speech and swallowing, as well as the potential downstream effects to the related areas of language and literacy. We discuss this framework with specific reference to individuals with Down syndrome (DS). Individuals with DS experience known craniofacial anomalies that impact their oropharyngeal somatosensation and skilled motor output for functional oral-pharyngeal activities such as speech and swallowing. Given the increased risk of dysphagia and "silent" aspiration in individuals with DS, it is likely somatosensory deficits are present as well. The purpose of this paper is to review the functional impact of structural and sensory alterations on skilled orofacial behaviors in DS as well as related skills in language and literacy development. We briefly discuss how the basis of this framework can be used to direct future research studies in swallowing, speech, and language and be applied to other clinical populations.

TÍTULO / TITLE:   - Family-professional collaborative intervention via telehealth with an infant with Down syndrome and visual impairment: a case report

REVISTA / JOURNAL:    - Physiother Theory Pract. 2023 Aug 4;1-10. doi: 10.1080/09593985.2023.2244067.

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AUTORES / AUTHORS: - Lara de Almeida Rodrigues et al

INSTITUCIÓN / INSTITUTION: - Graduate Program in Rehabilitation Sciences, School of Physical Education, Physical Therapy and Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 

RESUMEN / SUMMARY: - Background: Collaborative interventions, involving partnerships between professionals and families, make it possible to actively engage families in the rehabilitation process. However, no study was found that used a physiotherapy intervention via telehealth for infants with Down syndrome (DS). Objective: Describe the case report of a family-professional collaborative intervention via telehealth for an infant with Down syndrome and visual impairment during the COVID-19 pandemic. Case description: A male infant five months old participated in a collaborative intervention for a period of eight weeks. Three goals were set with the family, and a goal-oriented home program, involving visual stimulation strategies, was organized. Outcomes: Two goals were achieved. The family scored changes in performance and satisfaction with the infants performance according to the adapted Canadian Occupational Performance Measure. Improvement of motor skills was verified by Alberta Infant Motor Scale and changes in mobility and daily activities performance were measured by the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test. Conclusion: The use of family-professional collaborative intervention via telehealth during the COVID-19 pandemic shows promising results for achieving the goals established by the family collaboratively with the physical therapists.

TÍTULO / TITLE:   - Expressive language sampling and outcome measures for treatment trials in fragile X and Down syndromes: composite scores and psychometric properties

REVISTA / JOURNAL:    - Sci Rep. 2023 Jun 7;13(1):9267. doi: 10.1038/s41598-023-36087-3.

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AUTORES / AUTHORS: - Leonard Abbeduto et al

INSTITUCIÓN / INSTITUTION: - MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis Health, 2828 50Th St., Sacramento, CA, 95817, USA 

RESUMEN / SUMMARY: - The lack of psychometrically sound outcome measures has been a barrier to evaluating the efficacy of treatments proposed for core symptoms of intellectual disability (ID). Research on Expressive Language Sampling (ELS) procedures suggest it is a promising approach to measuring treatment efficacy. ELS entails collecting samples of a participants talk in interactions with an examiner that are naturalistic but sufficiently structured to ensure consistency and limit examiner effects on the language produced. In this study, we extended previous research on ELS by analyzing an existing dataset to determine whether psychometrically adequate composite scores reflecting multiple dimensions of language can be derived from ELS procedures administered to 6- to 23-year-olds with fragile X syndrome (n = 80) or Down syndrome (n = 78). Data came from ELS conversation and narration procedures administered twice in a 4-week test-retest interval. We found that several composites emerged from variables indexing syntax, vocabulary, planning processes, speech articulation, and talkativeness, although there were some differences in the composites for the two syndromes. Evidence of strong test-retest reliability and construct validity of two of three composites were obtained for each syndrome. Situations in which the composite scores would be useful in evaluating treatment efficacy are outlined.

TÍTULO / TITLE:   - Perceptions of families with adolescents utilizing augmentative and alternative communication technology: A qualitative approach

REVISTA / JOURNAL:    - J Pediatr Nurs. 2023 Jul-Aug;71:e46-e56. doi: 10.1016/j.pedn.2023.04.014. Epub 2023 Apr 29.

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AUTORES / AUTHORS: - Patricia West et al

INSTITUCIÓN / INSTITUTION: - College of Nursing, Michigan State University, 1355 Bogue Street, Life Science, East Lansing, MI 48824, United States. 

RESUMEN / SUMMARY: - Purpose: Although family involvement is critical to successful augmentative and alternative communication (AAC) device utilization, little is known about how families adapt to technology. The aim of this qualitative study was to explore parent-reported factors contributing to family adaptation among families with adolescents diagnosed with autism and/or Down syndrome (DS) utilizing AAC technology. This study describes families experiences related to several interacting variables of the Resiliency Model, including demand, type, appraisal, resources, and problem-solving/coping, that helped shape the outcome of adaptation to AAC technology. Nurses are well-positioned in a variety of practice settings to assess vulnerable families and assist with identifying resources and navigating complex service systems. Design and methods: Semi-structured interviews were conducted with eight parents of adolescents with autism and/or DS (aged 13-18) recruited through online research registries, support organizations, and a social networking site. Recorded interviews were transcribed, and two independent reviewers coded and analyzed the data. Comparisons across all families thematic summaries were examined for patterns. Results: Five themes described aspects of family adaptation: Contextual Strains and Influences, Continuum of Person-First Approach, Opening Doors, Facilitators of Support, and Planning Is Key. Conclusions: Findings highlighted the challenges and demands associated with raising an adolescent using an AAC device, as well as the attributes, resources, perceptions, and strategies that either contributed or hindered family adaptation. Practice implications: AAC technology is readily available for adolescents with developmental disabilities. It is essential that nurses assess key adaptation components to support families in integrating and using the technology.