CITAS BIBLIOGRÁFICAS
REFERENCES

Marzo - Abril 2018
March - April 2018


Si desea consultar citas de rastreos anteriores, pulse aquí
If you wish to find citations from previous searches, please click

Aging - Envejecimiento

TÍTULO / TITLE:   - 50 years with Down syndrome: A longitudinal study.

Enlace al Resumen

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2018 Mar 2. doi: 10.1111/jar.12438.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12438

AUTORES / AUTHORS: - Carr J; Collins S

INSTITUCIÓN / INSTITUTION: - Tizard Centre, University of Kent, Canterbury, UK. Faculty of Social Sciences, University of Essex, Colchester, UK. 

RESUMEN / SUMMARY: - BACKGROUND: A population sample of people with Down syndrome, studied from infancy, has now been followed up at the age of 50 years. From the original sample of 54, there were 27 still in the study at the age of 50, all but four of the losses resulting from deaths. METHODS: Intelligence and language skills were tested and daily living skills assessed. Memory/cognitive deterioration was examined using two test instruments. Other aspects of the people’s lives were examined via carers’ reports. RESULTS: Scores on verbal tests showed little change. Those on a non-verbal test, on self-help skills and on both memory tests showed some decline, even when the scores of those already suffering from dementia were discounted. CONCLUSIONS: At the age of 50, those not already diagnosed with dementia showed some decline on most tests. While this may include scores of people who subsequently develop dementia, it may also reflect the normal ageing process in this population.

TÍTULO / TITLE:   - Aging With Down Syndrome: The Dual Diagnosis: Alzheimer’s Disease and Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Am J Alzheimers Dis Other Demen. 2018 Jan 1:1533317518761093. doi: 10.1177/1533317518761093.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/1533317518761093

AUTORES / AUTHORS: - Cipriani G; et al.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - BACKGROUND: People with Down syndrome (DS) enjoy a longer life expectancy now than they ever have before and are therefore at greater risk of developing conditions associated with aging, including dementia. OBJECTIVES: To explore the phenomenon of dementia in DS. METHODS: Medline and Google Scholar searches were conducted for relevant articles, chapters, and books published until 2017. Search terms included Alzheimer’s disease, cognitive impairment, dementia, DS, and trisomy 21. Publications found through this indexed search were reviewed for further references. RESULTS AND CONCLUSIONS: Virtually, all subject aged 35 to 40 show key neuropathologic changes characteristic of Alzheimer’s disease, but only a part of them show clinical signs of dementia, usually around the age of 50 years. Early signs of dementia in people with DS may be different from those experienced by the general population. Failure to recognize this can delay diagnosis and subsequent interventions.

TÍTULO / TITLE:   - CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer’s disease following maternal choline supplementation.

Enlace al Resumen

REVISTA / JOURNAL:    - Hippocampus. 2018 Apr;28(4):251-268. doi: 10.1002/hipo.22832. Epub 2018 Feb 12.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/hipo.22832

AUTORES / AUTHORS: - Alldred MJ; et al.

INSTITUCIÓN / INSTITUTION: - Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York.; Department of Psychiatry, New York University Langone Medical Center, New York, New York. 

RESUMEN / SUMMARY: - Although there are changes in gene expression and alterations in neuronal density and afferent inputs in the forebrain of trisomic mouse models of Down syndrome (DS) and Alzheimer’s disease (AD), there is a lack of systematic assessments of gene expression and encoded proteins within individual vulnerable cell populations, precluding translational investigations at the molecular and cellular level. Further, no effective treatment exists to combat intellectual disability and basal forebrain cholinergic neurodegeneration seen in DS. To further our understanding of gene expression changes before and following cholinergic degeneration in a well-established mouse model of DS/AD, the Ts65Dn mouse, we assessed RNA expression levels from CA1 pyramidal neurons at two adult ages ( approximately 6 months of age and approximately 11 months of age) in both Ts65Dn and their normal disomic (2N) littermates. We further examined a therapeutic intervention, maternal choline supplementation (MCS), which has been previously shown to lessen dysfunction in spatial cognition and attention, and have protective effects on the survival of basal forebrain cholinergic neurons in the Ts65Dn mouse model. Results indicate that MCS normalized expression of several genes in key gene ontology categories, including synaptic plasticity, calcium signaling, and AD-associated neurodegeneration related to amyloid-beta peptide (Abeta) clearance. Specifically, normalized expression levels were found for endothelin converting enzyme-2 (Ece2), insulin degrading enzyme (Ide), Dyrk1a, and calcium/calmodulin-dependent protein kinase II (Camk2a), among other relevant genes. Single population expression profiling of vulnerable CA1 pyramidal neurons indicates that MCS is a viable therapeutic for long-term reprogramming of key transcripts involved in neuronal signaling that are dysregulated in the trisomic mouse brain which have translational potential for DS and AD.

TÍTULO / TITLE:   - Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study.

Enlace al Resumen

REVISTA / JOURNAL:    - Br J Psychiatry. 2018 Mar;212(3):155-160. doi: 10.1192/bjp.2017.21.

Enlace a la Editora de la Revista http://dx.doi.org/10.1192/bjp.2017.21

AUTORES / AUTHORS: - Eady N; Strydom A;

INSTITUCIÓN / INSTITUTION: - Division of Psychiatry,University College London,London;Institute of Psychiatry,Psychology and Neuroscience,King’s College London,London,UK;The LonDownS Consortium. 

RESUMEN / SUMMARY: - BACKGROUND: There is little evidence to guide pharmacological treatment in adults with Down syndrome and Alzheimer’s disease. Aims To investigate the effect of cholinesterase inhibitors or memantine on survival and function in adults with Down syndrome and Alzheimer’s disease. METHOD: This was a naturalistic longitudinal follow-up of a clinical cohort of 310 people with Down syndrome diagnosed with Alzheimer’s disease collected from specialist community services in England. RESULTS: Median survival time (5.59 years, 95% CI 4.67-6.67) for those on medication (n = 145, mainly cholinesterase inhibitors) was significantly greater than for those not prescribed medication (n = 165) (3.45 years, 95% CI 2.91-4.13, log-rank test P<0.001). Sequential assessments demonstrated an early effect in maintaining cognitive function. CONCLUSIONS: Cholinesterase inhibitors appear to offer benefit for people with Down syndrome and Alzheimer’s disease that is comparable with sporadic Alzheimer’s disease; a trial to test the effect of earlier treatment (prodromal Alzheimer’s disease) in Down syndrome may be indicated. Declaration of interest A.S. has undertaken consulting for Ono Pharmaceuticals, outside the submitted work. Z.W. has received a consultancy fee and grant from GE Healthcare, outside the submitted work.

TÍTULO / TITLE:   - Early and Selective Activation and Subsequent Alterations to the Unfolded Protein Response in Down Syndrome Mouse Models.

Enlace al Resumen

REVISTA / JOURNAL:    - J Alzheimers Dis. 2018;62(1):347-359. doi: 10.3233/JAD-170617.

Enlace a la Editora de la Revista http://dx.doi.org/10.3233/JAD-170617

AUTORES / AUTHORS: - Lanzillotta C; et al.

INSTITUCIÓN / INSTITUTION: - Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.; Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, KY, USA. 

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. DS individuals have an increased risk of developing Alzheimer’s disease (AD)-like pathology and dementia by the age of 40 due to the triplication of several genes involved in the formation of amyloid plaques and tau tangles. Further, DS and AD are characterized by the aberrant accumulation of unfolded/misfolded proteins resulting from over-burdened protein quality control systems. The accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers a cellular stress response called the unfolded protein response (UPR). Long-term activation of the UPR mediates neuronal dysfunction in AD. We hypothesized that the UPR is impacted in a mouse model of DS. To test this, we performed gene and protein expression analysis of ER stress markers in the Ts65Dn mouse model of DS at 3, 9, and 18 months. We identified activation of the PERK pathway in Ts65Dn DS mice at 3 months of age compared to euploid controls. We also determined that the early and overt UPR activation decreased with age, the UPR signal was significantly reduced by 18 months. Our data suggest that UPR activation in DS mouse models occurs early before consistent brain neurodegeneration and might be an essential contributor to dys-proteostasis.

TÍTULO / TITLE:   - Early striatal amyloid deposition distinguishes Down syndrome and autosomal dominant Alzheimer’s disease from late-onset amyloid deposition.

Enlace al Resumen

REVISTA / JOURNAL:    - Alzheimers Dement. 2018 Mar 1. pii: S1552-5260(18)30019-0. doi: 10.1016/j.jalz.2018.01.002.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jalz.2018.01.002

AUTORES / AUTHORS: - Cohen AD; et al.

INSTITUCIÓN / INSTITUTION: - Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic 

RESUMEN / SUMMARY: - INTRODUCTION: The objective of this study was to evaluate amyloid beta (Abeta) deposition patterns in different groups of cerebral beta amyloidosis: (1) nondemented with amyloid precursor protein overproduction (Down syndrome); (2) nondemented with abnormal processing of amyloid precursor protein (preclinical autosomal dominant Alzheimer disease); (3) presumed alteration in Abeta clearance with clinical symptoms (late-onset AD); and (4) presumed alterations in Abeta clearance (preclinical AD). METHODS: We performed whole-brain voxelwise comparison of cerebral Abeta between 23 Down syndrome, 10 preclinical autosomal dominant Alzheimer disease, 17 late-onset AD, and 16 preclinical AD subjects, using Pittsburgh Compound B-positron emission tomography. RESULTS: We found both Down syndrome and preclinical autosomal dominant Alzheimer disease shared a distinct pattern of increased bilateral striatal and thalamic Abeta deposition compared to late-onset AD and preclinical AD. CONCLUSION: Disorders associated with early-life alterations in amyloid precursor protein production or processing are associated with a distinct pattern of early striatal fibrillary Abeta deposition before significant cognitive impairment. A better understanding of this unique pattern could identify important mechanisms of Abeta deposition and possibly important targets for early intervention.

TÍTULO / TITLE:   - Down syndrome with posterior cortical atrophy.

Enlace al Resumen

REVISTA / JOURNAL:    - British Medical J (BMJ). Free access to the article (immediately). http://bmj.com/search.dtl

Enlace a la Editora de la Revista http://dx.doi.org/10.1136/bcr-2017-223108

AUTORES / AUTHORS: - CHU de Nantes, CMRR Neurologie, Nantes, France.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Down syndrome (DS) is caused by trisomy of chromosome 21. The average age of onset of Alzheimer’s disease (AD) ranged from 50 to 55 years in DS, with early symptoms usually characterised by changes in behaviour and executive dysfunction. On the other hand, posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterised by progressive impairment of visual functions in the absence of visual deficits and a pattern of atrophy involving posterior cortex. This syndrome is mostly caused by AD pathology. We report the case of patient with DS who developed PCA. While atypical variants of AD are commonly associated with an early age at onset, all focal forms of AD may potentially appear in DS. Specifying the phenotype has an impact on the care of DS patients and could help us to know the evolution. It could also provide a better understanding of the underlying mechanisms of focal forms.

TÍTULO / TITLE:   - Down Syndrome, Obesity, Alzheimer’s Disease, and Cancer: A Brief Review and Hypothesis.

Enlace al Resumen

REVISTA / JOURNAL:    - Brain Sci. 2018 Mar 24;8(4). pii: brainsci8040053. doi: 10.3390/brainsci8040053.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci8040053

AUTORES / AUTHORS: - Nixon DW

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Down syndrome (trisomy 21), a complex mix of physical, mental, and biochemical issues, includes an increased risk of Alzheimer’s disease and childhood leukemia, a decreased risk of other tumors, and a high frequency of overweight/obesity. Certain features related to the third copy of chromosome 21 (which carries the APP gene and several anti-angiogenesis genes) create an environment favorable for Alzheimer’s disease and unfavorable for cancer. This environment may be enhanced by two bioactive compounds from fat cells, leptin, and adiponectin. This paper outlines these fat-related disease mechanisms and suggests new avenues of research to reduce disease risk in Down syndrome.

Cardiology - Cardiología

TÍTULO / TITLE:   - Clinical, echocardiographic and analytical parameters in patients with atrioventricular septal defect with and without Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Med Clin (Barc). 2018 Mar 1. pii: S0025-7753(18)30052-6. doi: 10.1016/j.medcli.2018.01.005.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.medcli.2018.01.005

AUTORES / AUTHORS: - Rodriguez-Hernandez JL; Rodriguez-Gonzalez F; Martinez-Quintana E;

INSTITUCIÓN / INSTITUTION: - Med Clin (Barc). 2018 Mar 1. pii: S0025-7753(18)30052-6. doi: 10.1016/j.medcli.2018.01.005. 

RESUMEN / SUMMARY: - Servicio de Cardiologia, Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas de Gran Canaria, Las Palmas, España; Departamento de Ciencias Medicas y Quirurgicas, Facultad de Ciencias de la Salud, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, España.

TÍTULO / TITLE:   - Sinoatrial Node Disease in Adults with Down’s Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Ulster Med J. 2018 Jan;87(1):37-38. Epub 2018 Jan 31.

Enlace a la Editora de la Revista

AUTORES / AUTHORS: - Kennedy J; et al.

INSTITUCIÓN / INSTITUTION: - Department of Cardiology, Altnagelvin Area Hospital, Glenshane Road, Derry, Northern Ireland, UK BT47 6SB. 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Cardiac transplantation in children with Down syndrome, Turner syndrome, and other chromosomal anomalies: A multi-institutional outcomes analysis.

Enlace al Resumen

REVISTA / JOURNAL:    - J Heart Lung Transplant. 2018 Jan 31. pii: S1053-2498(18)31297-X. doi: 10.1016/j.healun.2018.01.1296

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.healun.2018.01.1296

AUTORES / AUTHORS: - Broda CR; ... Shamszad P

INSTITUCIÓN / INSTITUTION: - Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.  

RESUMEN / SUMMARY: - BACKGROUND: The purpose of this study was to describe the prevalence, characteristics, and outcomes in pediatric patients with chromosomal anomalies (CA) undergoing orthotopic heart transplantation (OHT). METHODS: A query of the database of the Pediatric Health Information System, a large administrative and billing database of 43 tertiary children’s hospitals, was performed for the Years 2004 to 2016. Pediatric patients who received OHT were analyzed based on presence and type of CA. CA analyzed included: Down syndrome (DS); Turner syndrome (TS)/gonadal dysgenesis; conditions due to anomaly of unspecified chromosome; autosomal deletion; microdeletion; and autosomal anomaly. Healthcare-associated charge analysis during hospitalization for OHT and survival after OHT were assessed. RESULTS: A total of 3,080 hospitalizations were identified in which OHTs were performed. Of these OHTs, 64 (2.1%) were performed in patients with a concomitant diagnosis of CA. The presence of CA did not confer a higher risk of in-hospital mortality after OHT (odds ratio 1.2 [0.5 to 3.2], p = 0.651). Differences in in-hospital mortality between different types of CA, including DS and TS, did not reach statistical significance. Survival at 1-year post-OHT was similar in patients with CA compared to those without CA (p = 0.248). Length of stay after OHT was longer in patients with CA: 76 (interquartile range [IQR] 76 to 142 days vs 49 [IQR 21 to 98] days) (p < 0.001), respectively. Overall adjusted hospital charges were significantly higher in the CA group: $1.2 million (IQR $740,000 to $2.2 million) vs $792,000 (IQR $425,000 to $1.5 million] (p < 0.001), respectively. CONCLUSIONS: CA is present in ~2% of pediatric patients undergoing OHT. The presence of CA was not associated with increased mortality in pediatric patients undergoing OHT. Limitations of this study include the small number of patients available for analysis and a likely highly selective cohort of patients with CA.

TÍTULO / TITLE:   - Is Trisomy 21 a Risk Factor for Rapid Progression of Pulmonary Arteriopathy?- Revisiting Histopathological Characteristics Using 282 Lung Biopsy Specimens.

Enlace al Resumen

REVISTA / JOURNAL:    - Circ J. 2018 Mar 16. doi: 10.1253/circj.CJ-17-0754.

Enlace a la Editora de la Revista http://dx.doi.org/10.1253/circj.CJ-17-0754

AUTORES / AUTHORS: - Masaki N; et al.

INSTITUCIÓN / INSTITUTION: - Division of Cardiovascular Surgery, Tohoku University Graduate School of Medicine. 

RESUMEN / SUMMARY: - Pulmonary hypertension (PH) is more progressive in trisomy 21 patients. However, pulmonary arteriopathic lesions in these patients have not been fully characterized histopathologically.Methods and Results:A retrospective review of a lung biopsy registry identified 282 patients: 188 patients with trisomy 21 (Group D) and 94 without (Group N). The mean age at lung biopsy was 3 and 7 months (P<0.0001). Pulmonary arterial pressure (PAP) and pulmonary vascular resistance were similar between the 2 groups. There were no significant differences in the proportion of patients with irreversible intimal lesions or the index of pulmonary vascular disease (IPVD; a measure of the degree of pulmonary arteriopathy progression) between the 2 groups. In addition, after propensity score matching for patient background (n=43 in each group), there were no significant differences in IPVD (P=0.29) or the ratio of irreversible intimal changes between the D and N groups (P=0.39). Multivariate analysis identified age (P<0.0001) and PAP (P=0.03) as the only risk factors for progression of pulmonary arteriopathy. CONCLUSIONS: Histopathologically, early progression of pulmonary arteriopathy in patients with trisomy 21 was not proved compared with patients without trisomy 21. Although we cannot exclude the possibility of bias in the Group D and N patients who were slated for lung biopsy, factors other than pulmonary arteriopathy may affect the marked progression of clinical PH in trisomy 21 patients.

TÍTULO / TITLE:   - Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

Enlace al Resumen

REVISTA / JOURNAL:    - Pediatr Int. 2018 Mar 25. doi: 10.1111/ped.13567.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/ped.13567

AUTORES / AUTHORS: - Kucuk M; et al.

INSTITUCIÓN / INSTITUTION: - Izmir Dr, Behcet Uz Children’s Hospital, Department of Pediatric Cardiology, Izmir, Turkey. 

RESUMEN / SUMMARY: - Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. METHODS: Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. RESULTS: Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. CONCLUSION: Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved.

TÍTULO / TITLE:   - Cerebral vasoreactivity and intima-media thickness in Down syndrome: A case-control study.

Enlace al Resumen

REVISTA / JOURNAL:    - J Neurol Sci. 2018 Feb 15;385:57-63

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jns.2017.11.013

AUTORES / AUTHORS: - Colella M; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurology, University of Messina, Italy; E.O. Ospedali Galliera, Genova, Italy.  

RESUMEN / SUMMARY: - Subjects with Down Syndrome (DS) have high prevalence of cerebral vascular amyloidosis, cognitive decline and dementia. In Alzheimer Disease, impaired vasoreactivity has been reported as the results of vascular amyloid deposition. Aim of our study was to verify presence of impaired cerebral vasoreactivity and to study carotid intima media-thickness (IMT) by carotid and transcranial ultrasound. We studied 25 DS and compared them with 25 age- and sex-matched normal controls. Vasomotor reactivity was evaluated by means of breath-holding index (BHI) test. There was no difference in IMT, both considering the two side separately (left: 0.70+/-0.10 vs 0.69+/-0.12mm, p=0.6) (right: 0.67+/-0.13 vs 0.68+/-0.10mm, p=0.5), and considering the sum of both sides (1.38+/-0.22 vs 1.38+/-0.23mm, p=1). There was a significant difference in peak systolic velocities (PSV) (139.75+/-27.67 vs. 123.89+/-25.73cm/s, p=0.04) and in pulsatility index (PI) (0.95+/-0.14 vs. 0.86+/-0.12, p=0.02). BHI was significantly lower in DS than in controls (1.15+/-0.38 vs 1.88+/-0.72, p<0.001). In conclusion, subjects with DS have increased PSV and PI, and show a reduction of BHI, expression of impaired vasomotor reserve, possibly due to micro-vascular impairment. Larger study with longitudinal design is needed to verify our data.

TÍTULO / TITLE:   - Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery.

Enlace al Resumen

REVISTA / JOURNAL:    - Pediatr Crit Care Med. 2018 Mar 15. doi: 10.1097/PCC.0000000000001537.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/PCC.0000000000001537

AUTORES / AUTHORS: - Goot BH; et al

INSTITUCIÓN / INSTITUTION: - The Heart Institute, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado, Denver School of Medicine, Aurora, CO. 

RESUMEN / SUMMARY: - To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. DESIGN: Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. SETTING: A 16-bed cardiac ICU at an university-affiliated hospital. PATIENTS: Forty-two patients (20 Down syndrome, 22 controls) were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. CONCLUSIONS: This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.

Ear/Nasal - Otorrinolaringología

TÍTULO / TITLE:   - Challenges and outcomes of cholesteatoma management in children with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Int J Pediatr Otorhinolaryngol. 2018 Mar;106:80-84. doi: 10.1016/j.ijporl.2018.01.016. Epub 2018 Feb

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ijporl.2018.01.016

AUTORES / AUTHORS: - Ghadersohi S; ... Billings KR

INSTITUCIÓN / INSTITUTION: - Ann & Robert H. Lurie Children’s Hospital of Chicago, Division of Pediatric Otolaryngology-Head and Neck Surgery, Chicago, IL, United States; Northwestern University Feinberg School of Medicine, Department of Otolaryngology-Head and Neck Su 

RESUMEN / SUMMARY: - The high incidence of chronic otitis media with effusion and Eustachian tube dysfunction in children with Down syndrome (DS) may predispose them to cholesteatoma formation. Establishing the diagnosis, choosing the appropriate operative intervention, and post-operative care can be challenging. OBJECTIVE: To describe management strategies for cholesteatoma diagnosis, surgical treatment, and post-operative management in children with Down syndrome. METHODS: Retrospective case series of 14 patients (17 total ears) with Down syndrome diagnosed with cholesteatoma over a 9-year period. RESULTS: A total of 14 patients with cholesteatoma (3 with bilateral disease) were analyzed. Thirteen ears (76.5%) had >/=2 tympanostomy tubes insertions prior to cholesteatoma diagnosis, and otorrhea and hearing loss were the most common presenting symptoms. Common pre-operative CT scan findings included mastoid sclerosis and ossicular erosion. The average age at first surgery was 9.8 years, and the average follow-up was 4.3 years. For acquired cholesteatoma, most ears were managed with canal wall up (CWU) approaches, but ultimately 6/15 (40.0%) required canal wall down (CWD) approaches. Postoperatively, 3 (20.0%) ears developed new tympanic membrane retraction pockets, but no recurrent cholesteatoma. Four (26.7%) ears developed recurrent disease, and 3 (20.0%) had residual disease at secondary procedures. Ossiculoplasty was performed in 4 ears. Twelve (70.6%) ears were rehabilitated with hearing aids or FM systems. CONCLUSIONS: The diagnosis of cholesteatoma in Down syndrome was associated with otorrhea, hearing loss, and CT scan findings of ossicular erosion and mastoid sclerosis. Most cases were managed with CWU surgical approaches. Hearing aid use was common post-operatively.

TÍTULO / TITLE:   - Lingual tonsillectomy in children with Down syndrome: Is it safe?

Enlace al Resumen

REVISTA / JOURNAL:    - Int J Pediatr Otorhinolaryngol. 2018 Feb;105:52-55. doi: 10.1016/j.ijporl.2017.11.027. Epub 2017 Nov

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ijporl.2017.11.027

AUTORES / AUTHORS: - Skirko JR;Jensen; ELFriedman NR;

INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology and Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, United States. 

RESUMEN / SUMMARY: - Evaluate peri-operative course and morbidity in children with Down syndrome (DS) who underwent a lingual tonsillectomy (LT) for residual obstructive sleep apnea (rOSA). METHODS: Retrospective case series for children with DS who underwent LT for rOSA from April 2011 to July 2016. Our primary outcomes were length of stay, readmission and complications. Surgical effectiveness was evaluated by change in the obstructive apnea-hypopnea-index(OAHI) and oxygen saturation nadir. RESULTS: Thirty-nine patients underwent LT. The mean length of stay was 1.3 days with n = 21(72%) staying one night. One subject (2.6%) had a post-operative bleed that did not require operative intervention. No other major complications occurred. In terms of effectiveness of surgery, twenty-nine children had sufficient data for inclusion. Median OAHI did not appreciably change (p = 0.07) from before surgery. Five subjects (17%) were cured of OSA (OAHI < 2/hour) and a mix of improvement and worsening was identified. The lowest oxygen saturation improved from 78% (SD = 7) before surgery to 82% (SD = 6) after surgery (p = 0.003). CONCLUSION: LT has a favorable post-operative course but its effectiveness at curing rOSA in the DS population has not been established/proven. Further research is indicated to determine optimal surgical management for DS children with LTH. 

TÍTULO / TITLE:   - External Auditory Canal Dimensions, Age, and Cerumen Retention or Impaction in Persons With Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Ann Otol Rhinol Laryngol. 2018 Apr;127(4):253-257. doi: 10.1177/0003489418756678. Epub 2018 Feb 9.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0003489418756678

AUTORES / AUTHORS: - Dy AES; Lapena JFF Jr.

INSTITUCIÓN / INSTITUTION: - 1 Department of Otorhinolaryngology, Philippine General Hospital, University of the Philippines Manila, Manila, Metro Manila, Philippines. 

RESUMEN / SUMMARY: - To investigate associations between age, external auditory canal (EAC) dimensions, and cerumen retention/impaction among persons with Down syndrome (DS). METHODS: This cross-sectional study evaluated EAC dimensions, cerumen retention/impaction, and middle ear status with pneumatoscopy after extraction in 130 persons with DS. Descriptive and inferential statistics correlated age, presence of impacted/retained cerumen, and EAC diameter. RESULTS: Of 260 ears in 67 males and 63 females with average age of 9.48 years, 72.3% (188) had EAC of 1 year (95% CI, 1.45-17.02, P = .011). The odds of having cerumen problems with an EAC diameter of

TÍTULO / TITLE:   - Wideband acoustic absorbance in children with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Braz J Otorhinolaryngol. 2018 Jan 10. pii: S1808-8694(18)30001-6. doi: 10.1016/j.bjorl.2017.12.006.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.bjorl.2017.12.006

AUTORES / AUTHORS: - Durante AS; et al

INSTITUCIÓN / INSTITUTION: - Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), Curso de Fonoaudiologia, Sao Paulo, SP, Brazil. 

RESUMEN / SUMMARY: - Tympanometry is currently the most frequently used tool for assessing the status of the middle ear, commonly assessed using a single 226Hz tone. However, the use of the Acoustic Immittance Measures with a wideband stimulus is a promising high-resolution evaluation, especially in individuals known to have middle ear alterations, such as Down syndrome patients. OBJECTIVE: The aim of this study was to analyze the acoustic absorbance measurements in children with Down syndrome. METHODS: Cross-sectional study, approved by the institution’s ethics committee. Data were collected from 30 children, with a mean age of 8.4 years, 15 with Down syndrome (DS-study group) and 15 children with typical development and no hearing complaints (control group). Energy absorbance was measured at frequencies of 226-8000Hz at ambient pressure and at peak pressure as a function of frequency using TITAN equipment. Statistical analysis was performed using the established level of statistical significance of 5%. RESULTS: With the 226Hz probe tone, 30 ears of the control group and 22 of the study group exhibited Type A tympanograms, whereas Type B was observed in eight children in the study group. The mean acoustic absorbance ratio of the study group was lower than that of the control group at frequencies centered at 2520Hz (p=0.008) for those with normal tympanometry results, and 226-4000Hz (p<0.03) for those with a Type B tympanometry curve. CONCLUSION: The low energy absorption in the presence of normal tympanograms in children with Down syndrome may suggest middle ear abnormalities.

Endocrinology/Nutrition - Endocrinología/Nutrición

TÍTULO / TITLE:   - Measuring feeding difficulties in toddlers with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Appetite. 2018 Mar 27;126:61-65. doi: 10.1016/j.appet.2018.03.018.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.appet.2018.03.018

AUTORES / AUTHORS: - van Dijk M; Lipke-Steenbeek W

INSTITUCIÓN / INSTITUTION: - Heymans Institute for Psychological Research, University of Groningen, Grote Kruisstraat 2/1, 9712 TS, Groningen, The Netherlands.  

RESUMEN / SUMMARY: - Early feeding problems occur frequently across the population, but have a higher incidence in children with Down syndrome (DS). Early identification can possibly be improved with the help of a valid screening instrument based on caregiver reports. In a previous study, we investigated the concurrent validity of the Dutch version of the Montreal Children’s Hospital Feeding Scale (MCH-FS, SEP in Dutch) in a sample of typically developing toddlers, and we found a correlation between the score on the instrument and observed behavior during a regular meal. The current pilot study was a replication in a sample of children with DS (aged 1; 0-3; 0) and their primary caregivers (n=32). The results showed that children in the sample did not score higher on the SEP than children in their respective norm groups. In addition, when caregivers reported more symptoms of feeding problems on the SEP, children showed more food refusal and negative affect during the observed meal. This suggests that the screening instrument is particularly associated with negative mealtime interactions. This is in contrast with earlier results, which mainly indicated a relation with eating skills.

Gastroenterology - Gastroenterología

TÍTULO / TITLE:   - Prevalence of celiac disease in patients with Down syndrome: a meta-analysis.

Enlace al Resumen

REVISTA / JOURNAL:    - Oncotarget. 2017 Dec 23;9(4):5387-5396. doi: 10.18632/oncotarget.23624. eCollection 2018 Jan 12.

Enlace a la Editora de la Revista http://dx.doi.org/10.18632/oncotarget.23624

AUTORES / AUTHORS: - Du Y; et al

INSTITUCIÓN / INSTITUTION: - Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China. 

RESUMEN / SUMMARY: - The association between Down syndrome and celiac disease has been reported by many studies. However, the prevalence of celiac disease (CD) in Down syndrome (DS) varies considerably across studies (from 0 % to 19 %). The aim of this study was to use meta-analysis to exam the prevalence of CD in patients with DS. Methods: A systematic search of English articles from Pubmed, Web of Science and CNKI without year limitation. Data were extracted by two independent observers and pooled using a random effects model by the Comprehensive Meta-Analysis Version 2 software. Results: A pooled analysis, based on 31 studies included 4383 individuals, revealed prevalence of biopsy-confirmed CD of 5.8 % (95 % CI = 4.7-7.2 %) in patients with DS. Sub-group analysis showed a slightly higher prevalence of CD in children with DS (6.6 %; 17 studies), than in age mixed samples with both children and adults (5.1 %; 13 studies). In addition, most of the studies included in this meta-analysis were from Europe and America, with the prevalence of celiac disease of 6 % (21 studies) and 5.7 % (6 studies) in DS patients, respectively. Furthermore, meta-regression analysis suggested that proportion of antibody-positive individuals that underwent small intestine biopsy had moderating effect on the outcome of the meta-analysis. Conclusions: These results demonstrated that patients (children) with Down syndrome had high prevalence of CD (more than one in twenty). The prevalence is high enough to motivate screening CD in DS children.

TÍTULO / TITLE:   - Measuring feeding difficulties in toddlers with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Appetite. 2018 Mar 27;126:61-65. doi: 10.1016/j.appet.2018.03.018.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.appet.2018.03.018

AUTORES / AUTHORS: - van Dijk M; Lipke-Steenbeek W

INSTITUCIÓN / INSTITUTION: - Heymans Institute for Psychological Research, University of Groningen, Grote Kruisstraat 2/1, 9712 TS, Groningen, The Netherlands. 

RESUMEN / SUMMARY: - Early feeding problems occur frequently across the population, but have a higher incidence in children with Down syndrome (DS). Early identification can possibly be improved with the help of a valid screening instrument based on caregiver reports. In a previous study, we investigated the concurrent validity of the Dutch version of the Montreal Children’s Hospital Feeding Scale (MCH-FS, SEP in Dutch) in a sample of typically developing toddlers, and we found a correlation between the score on the instrument and observed behavior during a regular meal. The current pilot study was a replication in a sample of children with DS (aged 1; 0-3; 0) and their primary caregivers (n=32). The results showed that children in the sample did not score higher on the SEP than children in their respective norm groups. In addition, when caregivers reported more symptoms of feeding problems on the SEP, children showed more food refusal and negative affect during the observed meal. This suggests that the screening instrument is particularly associated with negative mealtime interactions. This is in contrast with earlier results, which mainly indicated a relation with eating skills.

TÍTULO / TITLE:   - Role of monocyte chemoattractant protein-1 in liver fibrosis with transient myeloproliferative disorder in down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Hepatol Commun. 2018 Feb 1;2(3):230-236. doi: 10.1002/hep4.1150. eCollection 2018 Mar.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/hep4.1150

AUTORES / AUTHORS: - Kobayashi K et al.

INSTITUCIÓN / INSTITUTION: - Department of PathologyKokuritsu Kenkyu Kaihatsu Hojin Kokuritsu Seiiku Iryo Kenkyu CenterTokyoJapan. 

RESUMEN / SUMMARY: - Liver fibrosis is a common complication associated with transient myeloproliferative disorder (TMD) in Down syndrome (DS). The exact molecular pathogenesis that regulates disease progression is largely unknown. We recently found serum and/or urinary monocyte chemoattractant protein-1 (MCP-1) as a novel biomarker of liver fibrosis. This study was an in vitro analysis to investigate the fibrogenic activity of MCP-1 using the collagen-producing LX-2 human hepatic stellate cell line. We also examined the fibrogenic activity of serum from a male neonate with DS in whom late-onset liver fibrosis developed even after the resolution of TMD. MCP-1 stimulated both cell growth and collagen synthesis of LX-2 in a dose-dependent manner. Patient serum obtained during the active disease phase significantly up-regulated fibrogenic activity, which was suppressed in the presence of MCP-1-blocking antibody. Transient transforming growth factor beta 1 stimulation primed LX-2 to induce prolonged hypersecretion of MCP-1 in the culture supernatant and in collagen synthesis, which was suppressed with MCP-1 blocking antibody as well. Conclusion: MCP-1 accounts for the prolonged activation of collagen-producing hepatic stellate cells in both a paracrine and autocrine manner, thereby promoting liver fibrosis. Anti-cytokine therapy targeting the fibrogenic cytokines of MCP-1, for example, herbal medicine, could provide a new therapeutic intervention for liver fibrosis associated with TMD in DS. (Hepatology Communications 2018;2:230-236).

Genetics - Genética

TÍTULO / TITLE:   - Association between DSCR4 gene methylation in plasma in early pregnancy and Down’s syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Exp Ther Med. 2018 Mar;15(3):2749-2754. doi: 10.3892/etm.2018.5754. Epub 2018 Jan 16.

Enlace a la Editora de la Revista http://dx.doi.org/10.3892/etm.2018.5754

AUTORES / AUTHORS: - Hu L; Zhou C;

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China. 

RESUMEN / SUMMARY: - Down’s syndrome (DS), a chromosomal abnormal genetic disease caused by a local or total copy of chromosome 21, leads to patients suffering from delayed body growth, special facies, mild to moderate mental retardation and other symptoms, seriously affecting the life of patients. The aim of the present study was to examine the association between Down’s syndrome critical region 4 (DSCR4) gene methylation in plasma in high-risk pregnant women with DS in early pregnancy (hereinafter referred to as pregnant women in early pregnancy) and DS, in order to screen new epigenetic markers for the clinical diagnosis of DS. DNA in peripheral blood cells and plasma in pregnant women in early pregnancy were treated with hydrosulphite. DSCR4 genes with different methylation levels were amplified by methylation-specific polymerase chain reaction (PCR), and the methylation difference of the CpG site of the DSCR4 amplification product in peripheral blood DNA was verified via restriction endonuclease analysis. The expression of DSCR4 with different methylation levels in peripheral blood of pregnant women in early pregnancy were detected via reverse transcriptase-quantitative PCR (RT-qPCR), and the DSCR4 gene functions were studied via the intervention in DSCR4 expression with small interfering RNA (siRNA). Methylation-specific PCR and restriction endonuclease analysis revealed that DSCR4 genes were differentially methylated in peripheral blood DNA in pregnant women in early pregnancy. Additionally, DSCR4 showed a low methylation status in plasma but a high methylation status in peripheral blood cells. RT-qPCR revealed that non-methylated DSCR4 was highly expressed in the peripheral blood of pregnant women in early pregnancy, and thus was an epigenetic marker of fetal DS. siRNA results showed that the downregulation of DSCR4 inhibited cell migration and invasion, but had no effect on cell proliferation. The results suggest that the DSCR4 gene was differentially methylated in peripheral b

TÍTULO / TITLE:   - The genetic background and application of Down syndrome mouse models.

Enlace al Resumen

REVISTA / JOURNAL:    - Yi Chuan. 2018 Mar 20;40(3):207-217. doi: 10.16288/j.yczz.17-279.

Enlace a la Editora de la Revista http://dx.doi.org/10.16288/j.yczz.17-279

AUTORES / AUTHORS: - Meng XW; et al

INSTITUCIÓN / INSTITUTION: - Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China. 

RESUMEN / SUMMARY: - Down syndrome (DS), trisomy chromosome 21 (Hsa21), is the most common genetic disease caused by chromosome aberration in the human genome. Modeling DS in mice has been challenging since the orthologs of Hsa21 genes map to separate segments of three mouse chromosomes, Mmu16, Mmu17, and Mmu10. Although the early Ts65Dn mouse model exhibited various DS phenotypes, the duplicated fragments were randomly generated by ionizing radiation and did not include all Hsa21 orthologs. In 2004, the successful use of the Cre/LoxP recombination technique in chromosomal engineering in the construction of the Ts1Rhr mouse strain solved the problem of duplication of specific chromosome segment, resulting in the establishment of specific DS mouse models with accurate triplication of particular genes and associated phenotypes. In this review, we briefly introduce the different DS mouse models and discuss their advantages and limitations by focusing on the triplication of Hsa21 orthologs and manifestations of DS phenotypes, thereby providing some references for the selection of specific mouse models in DS research.

TÍTULO / TITLE:   - Widespread domain-like perturbations of DNA methylation in whole blood of Down syndrome neonates.

Enlace al Resumen

REVISTA / JOURNAL:    - PLoS One. 2018 Mar 30;13(3):e0194938. doi: 10.1371/journal.pone.0194938. eCollection 2018.

Enlace a la Editora de la Revista http://dx.doi.org/10.1371/journal.pone.0194938

AUTORES / AUTHORS: - Henneman P et al.

INSTITUCIÓN / INSTITUTION: - Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. 

RESUMEN / SUMMARY: - Down syndrome (DS) is the most frequent genetic cause of intellectual disability. Despite the fact that more than 50 years have passed since the discovery of its genetic aberrations, the exact pathogenesis of the DS phenotype has remained largely unexplained. It was recently hypothesized that the DS pathogenesis involves complex (epi)genetic, molecular and cellular determinants. To date, many reports have addressed epigenetic aberrations associated with DS at different developmental stages/ages and tissue types, but to our best knowledge not in DS newborns. This study aimed to investigate genome-wide methylation patterns in DS newborns compared to non-trisomic newborns. METHOD: We analyzed blood samples obtained from ten newborns with DS and five age-matched non-trisomic newborns. Epigenetic profiles were obtained from extracted DNA using the Illumina Infinium 450K array. Since aberrant blood cell distribution is known to be present in DS, we applied two distinct models: with and without correction for estimated blood cell distribution. RESULTS: Differentially methylated position (DMP) analysis of the uncorrected model detected 19525 significant hits (51,2% hypomethylated). In the corrected model, we found 121953 significant DMPs (49,8% hypomethylated). Independent of the used model we observed a chromosome 21 dosage effect. Moreover, we detected 46 and 145 differentially methylated regions in the uncorrected and corrected model respectively, both showing hypomethylation overrepresentation. Replication analyses of DMPs and DMRs found by Bacalini et al. (2015) showed a large overlap. CONCLUSION: In this study, we found methylation profile differences between DS newborns and controls reflecting a systematically affected epigenetic profile. The observed chromosome 21 dosage effect suggests the involvement of affected essential regulatory factors/regions or altered expression of chromatin modeling enzymes located on chromosome 21. Additional research is necessary to sub

TÍTULO / TITLE:   - Interrelation of the gene 4dkn1a (rs 1801270) polymorphic state and level of development of caries in children with down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Georgian Med News. 2018 Feb;(Issue):112-116.

Enlace a la Editora de la Revista

AUTORES / AUTHORS: - Nazaryan R; et al.

INSTITUCIÓN / INSTITUTION: - Kharkiv National Medical University, Kharkiv National University named after V.Karazin, Ukraine. 

RESUMEN / SUMMARY: - Study is devoted for rs1801270 polymorphism of CDKN1A gene due to the level of intensity of caries development in children with Down syndrome. The full development of oral cavity organs is ensured through a complex of genes whose protein products control different stages of this difficult process. Changes in gene structure, as well as disturbance of their expression may lead to abnormalities of development of teeth and periodontal tissues. Analysis of the polymorphism of CDKN1A gene Ser31Arg in children living in Kharkiv region has shown that the frequency of genotypes and alleles corresponds to the theoretically expected distribution by Hardy-Weinberg in the core (chi2=0.12) and control (chi2=1.29) groups. There is no significant differences in the frequency of alleles of CDKN1A gene in the group of healthy children and children with Down syndrome (p=0.978). There is an association of heterozygous option C/A of the studied marker Ser31Arg of CDKN1A gene with the level of intensity of caries development (by Leus) in children with Down syndrome under 10 years old.

TÍTULO / TITLE:   - Down syndrome and microRNAs.

Enlace al Resumen

REVISTA / JOURNAL:    - Biomed Rep. 2018 Jan;8(1):11-16. doi: 10.3892/br.2017.1019. Epub 2017 Nov 17.

Enlace a la Editora de la Revista http://dx.doi.org/10.3892/br.2017.1019

AUTORES / AUTHORS: - Bras A; et al.

INSTITUCIÓN / INSTITUTION: - Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculty of Medical Sciences, NOVA University of Lisbon, 1169-056 Lisbon, Portugal. 

RESUMEN / SUMMARY: - In recent years numerous studies have indicated the importance of microRNAs (miRNA/miRs) in human pathology. Down syndrome (DS) is the most prevalent survivable chromosomal disorder and is attributed to trisomy 21 and the subsequent alteration of the dosage of genes located on this chromosome. A number of miRNAs are overexpressed in down syndrome, including miR-155, miR-802, miR- 125b-2, let-7c and miR-99a. This overexpression may contribute to the neuropathology, congenital heart defects, leukemia and low rate of solid tumor development observed in patients with DS. MiRNAs located on other chromosomes and with associated target genes on or off chromosome 21 may also be involved in the DS phenotype. In the present review, an overview of miRNAs and the haploinsufficiency and protein translation of specific miRNA targets in DS are discussed. This aimed to aid understanding of the pathogenesis of DS, and may contribute to the development of novel strategies for the prevention and treatment of the pathologies of DS.

Hematology/Oncology - Hematología/Oncología

TÍTULO / TITLE:   - Loss of Full-Length GATA1 Expression in Megakaryocytes Is a Sensitive and Specific Immunohistochemical Marker for the Diagnosis of Myeloid Proliferative Disorder Related to Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Am J Clin Pathol. 2018 Mar 7;149(4):300-309. doi: 10.1093/ajcp/aqy001.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/ajcp/aqy001

AUTORES / AUTHORS: - Lee WY; et al

INSTITUCIÓN / INSTITUTION: - Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA. 

RESUMEN / SUMMARY: - Objectives: Myeloid proliferative disorders associated with Down syndrome (MPD-DS), including transient abnormal myelopoiesis and myeloid leukemia associated with Down syndrome (DS), harbor mutations of GATA1, a transcription factor essential for erythroid and megakaryocytic development. These mutations result in a N-terminally truncated GATA1 (GATA1s) and prohibit the production of the full-length GATA1 (GATA1f). Here, we demonstrate the utility of immunohistochemical GATA1f reactivity in diagnosing MPD-DS. Methods: Immunohistochemical studies for GATA1f expression were performed on bone marrow biopsy specimens. Results: In all cases of MPD-DS, megakaryocytes lacked GATA1f expression. In contrast, GATA1f expression was detected in megakaryocytes in all specimen types from patients without DS (normal bone marrows, pediatric myelodysplastic syndrome, juvenile myelomonocytic leukemia, adult acute megakaryocytic leukemia [pediatric and adult; without trisomy 2]), as well as normal bone marrows from patients with DS. Conclusions: The lack of GATA1f expression is a sensitive and specific immunohistochemical marker for MPD-DS.

TÍTULO / TITLE:   - Down syndrome associated childhood myeloid leukemia with yet unreported acquired chromosomal abnormalities and a new potential adverse marker: dup(1)(q25q44).

Enlace al Resumen

REVISTA / JOURNAL:    - Mol Cytogenet. 2018 Mar 13;11:22. doi: 10.1186/s13039-018-0370-8. eCollection 2018.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13039-018-0370-8

AUTORES / AUTHORS: - Moassass F; et al.

INSTITUCIÓN / INSTITUTION: - Molecular Biology and Biotechnology Department, Human Genetics Division, Chromosomes Laboratory, Atomic Energy Commission of Syria, P.O. Box 6091, Damascus, Syria.0000 0000 9342 9009grid.459405.9 

RESUMEN / SUMMARY: - Children with constitutional trisomy 21, i.e. Down syndrome (DS, OMIM -190685) have a 10 to 20-fold increased risk for a hematopoietic malignancy. They may suffer from acute lymphoblastic leukemia or acute myeloid leukemia (AML). AML referred to as myeloid leukemia of Down syndrome (ML-DS) is observed especially after birth at an early gestational age and characterized by enhanced white blood cell count, failure of spontaneous remission, liver fibrosis or liver dysfunction, and is significantly associated with early death. There are only few studies yet focusing on the clonal cytogenetic changes during evolution of ML-DS. Case presentation: In a 1.4-year-old boy with DS an immunophenotype consistent with AML-M1 according to French-American-British (FAB) classification was diagnoses. Cytogenetic and molecular cytogenetic analyses revealed, besides constitutional free trisomy 21, an unbalanced translocation as der(16)t(1;16)(q25.3;q24), plus a balanced translocation t(3;20)(q25;q13.1). A poor clinical outcome was observed here. Conclusions: To the best of our knowledge, an ML-DS case associated with identical acquired chromosomal abnormalities was not previously reported. Our findings suggest that especially partial trisomy 1q25 to 1q44 may be indicative for a poor prognosis in ML-DS.

TÍTULO / TITLE:   - Role of monocyte chemoattractant protein-1 in liver fibrosis with transient myeloproliferative disorder in down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Hepatol Commun. 2018 Feb 1;2(3):230-236. doi: 10.1002/hep4.1150. eCollection 2018 Mar.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/hep4.1150

AUTORES / AUTHORS: - Kobayashi K et al.

INSTITUCIÓN / INSTITUTION: - Department of PathologyKokuritsu Kenkyu Kaihatsu Hojin Kokuritsu Seiiku Iryo Kenkyu CenterTokyoJapan. 

RESUMEN / SUMMARY: - Liver fibrosis is a common complication associated with transient myeloproliferative disorder (TMD) in Down syndrome (DS). The exact molecular pathogenesis that regulates disease progression is largely unknown. We recently found serum and/or urinary monocyte chemoattractant protein-1 (MCP-1) as a novel biomarker of liver fibrosis. This study was an in vitro analysis to investigate the fibrogenic activity of MCP-1 using the collagen-producing LX-2 human hepatic stellate cell line. We also examined the fibrogenic activity of serum from a male neonate with DS in whom late-onset liver fibrosis developed even after the resolution of TMD. MCP-1 stimulated both cell growth and collagen synthesis of LX-2 in a dose-dependent manner. Patient serum obtained during the active disease phase significantly up-regulated fibrogenic activity, which was suppressed in the presence of MCP-1-blocking antibody. Transient transforming growth factor beta 1 stimulation primed LX-2 to induce prolonged hypersecretion of MCP-1 in the culture supernatant and in collagen synthesis, which was suppressed with MCP-1 blocking antibody as well. Conclusion: MCP-1 accounts for the prolonged activation of collagen-producing hepatic stellate cells in both a paracrine and autocrine manner, thereby promoting liver fibrosis. Anti-cytokine therapy targeting the fibrogenic cytokines of MCP-1, for example, herbal medicine, could provide a new therapeutic intervention for liver fibrosis associated with TMD in DS. (Hepatology Communications 2018;2:230-236).

Molecular biology/Biochemistry - Biología molecular/Bioquímica

TÍTULO / TITLE:   - Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism.

Enlace al Resumen

REVISTA / JOURNAL:    - Sci Rep. 2018 Feb 14;8(1):2977. doi: 10.1038/s41598-018-20834-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-018-20834-y

AUTORES / AUTHORS: - Caracausi M; et al

INSTITUCIÓN / INSTITUTION: - Department of Experimental, Diagnostic and Specialty Medicine, (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126, Bologna, BO, Italy. 

RESUMEN / SUMMARY: - Down syndrome (DS) is caused by the presence of a supernumerary copy of the human chromosome 21 (Hsa21) and is the most frequent genetic cause of intellectual disability (ID). Key traits of DS are the distinctive facies and cognitive impairment. We conducted for the first time an analysis of the Nuclear Magnetic Resonance (NMR)-detectable part of the metabolome in plasma and urine samples, studying 67 subjects with DS and 29 normal subjects as controls selected among DS siblings. Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to of 80% accuracy) between the DS and the control groups. The univariate analysis of plasma and urine revealed a significant alteration for some interesting metabolites. Remarkably, most of the altered concentrations were consistent with the 3:2 gene dosage model, suggesting effects caused by the presence of three copies of Hsa21 rather than two: DS/normal ratio in plasma was 1.23 (pyruvate), 1.47 (succinate), 1.39 (fumarate), 1.33 (lactate), 1.4 (formate). Several significantly altered metabolites are produced at the beginning or during the Krebs cycle. Accounting for sex, age and fasting state did not significantly affect the main result of both multivariate and univariate analysis.

Neurobiology - Neurobiología

TÍTULO / TITLE:   - Developmental excitatory-to-inhibitory GABA polarity switch is delayed in Ts65Dn mice, a genetic model of Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Neurobiol Dis. 2018 Mar 14;115:1-8. doi: 10.1016/j.nbd.2018.03.005.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2018.03.005

AUTORES / AUTHORS: - Lysenko LV; ... Kleschevnikov AM

INSTITUCIÓN / INSTITUTION: - Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla 92093, CA, United States; School of Biomedicine, Far Eastern Federal University, Sukhanova 8, Vladivostok 690950, Russian Federation. 

RESUMEN / SUMMARY: - Down syndrome (DS) is the most frequent genetic cause of developmental abnormalities leading to intellectual disability. One notable phenomenon affecting the formation of nascent neural circuits during late developmental periods is developmental switch of GABA action from depolarizing to hyperpolarizing mode. We examined properties of this switch in DS using primary cultures and acute hippocampal slices from Ts65Dn mice, a genetic model of DS. Cultures of DIV3-DIV13 Ts65Dn and control normosomic (2N) neurons were loaded with FURA-2AM, and GABA action was assessed using local applications. In 2N cultures, the number of GABA-activated cells dropped from ~100% to 20% between postnatal days 3-13 (P3-P13) reflecting the switch in GABA action polarity. In Ts65Dn cultures, the timing of this switch was delayed by 2-3days. Next, microelectrode recordings of multi-unit activity (MUA) were performed in CA3 slices during bath application of the GABAA agonist isoguvacine. MUA frequency was increased in P8-P12 and reduced in P14-P22 slices reflecting the switch of GABA action from excitatory to inhibitory mode. The timing of this switch was delayed in Ts65Dn by approximately 2days. Finally, frequency of giant depolarizing potentials (GDPs), a form of primordial neural activity, was significantly increased in slices from Ts65Dn pups at P12 and P14. These experimental evidences show that GABA action polarity switch is delayed in Ts65Dn model of DS, and that these changes lead to a delay in maturation of nascent neural circuits. These alterations may affect properties of neural circuits in adult animals and, therefore, represent a prospective target for pharmacotherapy of cognitive impairment in DS.

TÍTULO / TITLE:   - Sleep Behavior and EEG Oscillations in Aged Dp(16)1Yey/+ Mice: A Down Syndrome Model.

Enlace al Resumen

REVISTA / JOURNAL:    - Neuroscience. 2018 Apr 15;376:117-126. doi: 10.1016/j.neuroscience.2018.02.009. Epub 2018 Feb 16.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.neuroscience.2018.02.009

AUTORES / AUTHORS: - Levenga J; ... Hoeffer CA

INSTITUCIÓN / INSTITUTION: - Institute for Behavioral Genetics, University of Colorado, Boulder, United States; Department of Integrative Physiology, University of Colorado, Boulder, United States; Linda Crnic Institute, Anschutz Medical School, Denver, CO, United Stat 

RESUMEN / SUMMARY: - Down syndrome (DS) results from the triplication of genes located on human chromosome 21 (Hsa21). Though many cognitive and behavioral impairments are associated with DS, sleep disturbances remain poorly understood despite being a reported phenotype in approximately 60% of individuals diagnosed with DS. In this study, sleep and electroencephalography (EEG) oscillations were recorded from aged (12-14mos.) Dp(16)1Yey/+ mice (Dp16), a mouse model of DS. We observed disrupted sleep demonstrated by increased activity during the dark phase and increased time awake at the expense of NREM sleep compared to wild-type mice. In addition, we found that Dp16 mice display significant differences in relative EEG power distribution among oscillation frequencies in both sleep and awake states. These results in Dp16 mice are consistent with sleep disturbances found in individuals with DS, and the abnormal EEG oscillations in aged Dp16 mice suggest a potential role for GABAergic activity in these sleep and EEG abnormalities. These sleep and EEG data reflect underlying differences in neuronal activity at the network level and thus are causative agents rather than merely symptoms of DS.

TÍTULO / TITLE:   - Rapid forgetting of social learning in the Ts65Dn mouse model of Down syndrome: New evidence for hippocampal dysfunction.

Enlace al Resumen

REVISTA / JOURNAL:    - Behav Neurosci. 2018 Feb;132(1):51-56. doi: 10.1037/bne0000227.

Enlace a la Editora de la Revista http://dx.doi.org/10.1037/bne0000227

AUTORES / AUTHORS: - Powers BE; et al

INSTITUCIÓN / INSTITUTION: - Division of Nutritional Sciences, Cornell University. 

RESUMEN / SUMMARY: - The Ts65Dn mouse model of Down syndrome recapitulates the hallmark areas of dysfunction that characterize the human disorder, including impaired performance in tasks designed to tap hippocampus-dependent learning and memory. Unfortunately, performance in the water maze tasks most commonly used for this purpose can be affected by behavioral and/or physiological abnormalities characteristic of Ts65Dn mice (e.g., thigmotaxis, susceptibility to hypothermia, stress reactivity), which complicates interpretation of impaired performance. The current study assessed hippocampal function in Ts65Dn mice using the social transmission of food preference (STFP) paradigm, which does not entail water escape or aversive reinforcement, and thus avoids these interpretive confounds. We tested Ts65Dn mice and disomic controls on this task using 1- and 7-day retention intervals. The Ts65Dn mice exhibited normal learning and memory following the 1-day retention interval, but rapid forgetting of the socially acquired information, evidenced by impaired performance following the 7-day retention interval. The STFP paradigm can be a valuable tool for studies using the Ts65Dn mouse model to evaluate potential therapies that may ameliorate hippocampal dysfunction and aging-related cognitive decline in Down syndrome.

TÍTULO / TITLE:   - Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons.

Enlace al Resumen

REVISTA / JOURNAL:    - Stem Cell Reports. 2018 Feb 28. pii: S2213-6711(18)30069-9. doi: 10.1016/j.stemcr.2018.02.001.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.stemcr.2018.02.001

AUTORES / AUTHORS: - Huo HQ; et al.

INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China; Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China 

RESUMEN / SUMMARY: - The brain of Down syndrome (DS) patients exhibits fewer interneurons in the cerebral cortex, but its underlying mechanism remains unknown. By morphometric analysis of cortical interneurons generated from DS and euploid induced pluripotent stem cells (iPSCs), we found that DS GABA neurons are smaller and with fewer neuronal processes. The proportion of calretinin over calbindin GABA neurons is reduced, and the neuronal migration capacity is decreased. Such phenotypes were replicated following transplantation of the DS GABAergic progenitors into the mouse medial septum. Gene expression profiling revealed altered cell migratory pathways, and correction of the PAK1 pathway mitigated the cell migration deficit in vitro. These results suggest that impaired migration of DS GABAergic neurons may contribute to the reduced number of interneurons in the cerebral cortex and hippocampus in DS patients.

TÍTULO / TITLE:   - Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice.

Enlace al Resumen

REVISTA / JOURNAL:    - Elife. 2018 Feb 27;7. pii: 31543. doi: 10.7554/eLife.31543.

Enlace a la Editora de la Revista http://dx.doi.org/10.7554/eLife.31543

AUTORES / AUTHORS: - Raveau M et al.

INSTITUCIÓN / INSTITUTION: - Laboratory for Neurogenetics, RIKEN, Brain Science Institute, Saitama, Japan. 

RESUMEN / SUMMARY: - Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the ‘over-suppression’ theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice.

TÍTULO / TITLE:   - DYRK1A inhibition and cognitive rescue in a Down syndrome mouse model are induced by new fluoro-DANDY derivatives.

Enlace al Resumen

REVISTA / JOURNAL:    - Sci Rep. 2018 Feb 12;8(1):2859. doi: 10.1038/s41598-018-20984-z.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-018-20984-z

AUTORES / AUTHORS: - Neumann F; et al.

INSTITUCIÓN / INSTITUTION: - : Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Universite Paris-Sud, Universite Paris-Saclay, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.  

RESUMEN / SUMMARY: - Inhibition of DYRK1A kinase, produced by chromosome 21 and consequently overproduced in trisomy 21 subjects, has been suggested as a therapeutic approach to treating the cognitive deficiencies observed in Down syndrome (DS). We now report the synthesis and potent DYRK1A inhibitory activities of fluoro derivatives of 3,5-di(polyhydroxyaryl)-7-azaindoles (F-DANDYs). One of these compounds (3-(4-fluorophenyl)-5-(3,4-dihydroxyphenyl)-1H-pyrrolo[2,3-b]pyridine, 5a) was selected for in vivo studies of cognitive rescuing effects in a standard mouse model of DS (Ts65Dn line). Using the Morris water maze task, Ts65Dn mice treated i.p. with 20 mg/kg of 5a performed significantly better than Ts65Dn mice treated with placebo, confirming the promnesiant effect of 5a in the trisomic mice. Overall, these results demonstrate for the first time that selective and competitive inhibition of DYRK1A kinase by the F-DANDY derivative 5a may provide a viable treatment strategy for combating the memory and learning deficiencies encountered in DS.

Neurology - Neurología

TÍTULO / TITLE:   - Abnormal development of the inferior temporal region in fetuses with down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Brain Pathol. 2018 Mar 6. doi: 10.1111/bpa.12605.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/bpa.12605

AUTORES / AUTHORS: - Guidi S; ... Bartesaghi R

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

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetic condition associated with impairment in several cognitive domains. Previous evidence showed a notable neurogenesis reduction in the hippocampal region of DS fetuses, which may account for the impairment of declarative memory that characterizes DS starting from early life stages. The fusiform gyrus (FG) and the inferior temporal gyrus (ITG) play a key role in visual recognition memory, a function that is impaired in children and adults with DS. The goal of the current study was to establish whether fetuses with DS (17-21 weeks of gestation) exhibit neuroanatomical alterations in the FG and ITG that may underlie recognition memory impairment. We found that the FG and ITG of fetuses with DS had a reduced thickness and fewer cells in comparison with euploid fetuses. Moreover, DS fetuses had fewer cells expressing the neuronal marker NeuN than euploid fetuses, but a similar number of cells expressing the astrocytic marker GFAP and, consequently, a higher percentage of astrocytes. Immunohistochemistry for calretinin (CR), a marker of GABAergic interneurons, showed that in DS fetuses the ratio of CR-positive versus CR-negative cells was greater than in euploid fetuses, both in the FG (+77%) and ITG (+61%). An increased ratio of CR-positive versus CR-negative cells was also found in the entorhinal cortex, hippocampus and dentate gyrus. Results provide novel evidence that the FG and ITG of DS fetuses exhibit numerous developmental defects. These defects may underlie the functional alterations in visual recognition memory observed in children with DS. This article is protected by copyright. All rights reserved.

TÍTULO / TITLE:   - Cerebral Angiography in Moyamoya Syndrome Secondary to Vasculopathy in Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - J Vasc Interv Neurol. 2017 Dec;9(6):55-56.

Enlace a la Editora de la Revista

AUTORES / AUTHORS: - Shehabeldin M; et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: -

Ophtalmology - Oftalmología

TÍTULO / TITLE:   - Repeatability of Monocular Acuity Testing in Adults with and without Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Optom Vis Sci. 2018 Mar;95(3):202-211. doi: 10.1097/OPX.0000000000001185.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/OPX.0000000000001185

AUTORES / AUTHORS: - Ravikumar A et al.

INSTITUCIÓN / INSTITUTION: - Texas Institute for Measurement, Evaluation and Statistics, University of Houston, Houston, Texas 

RESUMEN / SUMMARY: - Individuals with Down syndrome may experience greater difficulty reliably performing visual acuity (VA) tests because of intellectual disability and limitations in visual quality. This study evaluated the repeatability of acuity (Bailey-Lovie [BL] and HOTV) in subjects with and without Down syndrome. METHODS: High-contrast VA was measured in both eyes of 30 subjects with Down syndrome (mean, 30 years; range, 18 to 50 years) and 24 control subjects without Down syndrome (mean, 29 years; range, 18 to 50 years). In the Down syndrome group, 23 subjects performed BL, and 7 subjects performed HOTV. All control subjects performed both BL and HOTV, but for HOTV analysis, only seven age-matched control subjects were included. For each eye, subjects performed VA three times on different charts (computer controlled, single-line display) until five total letters were missed on each chart. A repeated-measure ANOVA was used to compare the acuity measures between groups. RESULTS: The average logMAR VA for subjects with Down syndrome was approximately six lines worse than the control subjects (BL: Down syndrome = right eye: 0.51 +/- 0.16, left eye: 0.53 +/- 0.18; control = right eye: -0.06 +/- 0.06, left eye: -0.06 +/- 0.08, P < .0001; HOTV: Down syndrome = right eye: 0.47 +/- 0.19, left eye: 0.46 +/- 0.16; control: right eye = -0.11 +/- 0.09, left eye: -0.07 +/- 0.07, P < .001). Bailey-Lovie VA repeatability (1.96 * Sw * radical2) was 0.13 logMAR (6.5 letters) for Down syndrome and 0.09 logMAR (4.5 letters) for control subjects. HOTV VA repeatability was 0.16 logMAR (eight letters) for both Down syndrome and control subjects. CONCLUSIONS: Despite poorer acuity in individuals with Down syndrome, repeatability of VA measurements was comparable to control subjects for both BL and HOTV techniques.

TÍTULO / TITLE:   - Different visual development: norms for visual acuity in children with Down’s syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Clin Exp Optom. 2018 Mar 30. doi: 10.1111/cxo.12684.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/cxo.12684

AUTORES / AUTHORS: - Zahidi AA; et al

INSTITUCIÓN / INSTITUTION: - School of Optometry & Vision Sciences, Cardiff University, Cardiff, UK. 

RESUMEN / SUMMARY: - Visual acuity is known to be poorer in children with Down’s syndrome than in age-matched controls. However, to date, clinicians do not have access to norms for children with Down’s syndrome that allow differential discrimination of healthy from anomalous visual development in this population. METHODS: The Down’s Syndrome Vision Research Unit at Cardiff University has been monitoring visual development in a large cohort of children since 1992. Cross-sectional data on binocular visual acuity were retrospectively analysed for 159 children up to 12 years of age in order to establish binocular acuity norms. Longitudinal binocular acuity data were available for nine children who were seen regularly over the 12 years age-range. Monocular acuity was successfully recorded less often in the cohort, but analysis of scores for 69 children allowed assessment of inter-ocular acuity differences and binocular summation. RESULTS: In comparison with published norms for the various acuity tests used, binocular acuity was consistently poorer in children with Down’s syndrome from the age of three years and stabilised at around 0.25 logMAR from the age of four years. Inter-ocular acuity difference and binocular summation were both 0.06 logMAR, which is similar to the reported values in children without Down’s syndrome. CONCLUSIONS: The study provides eye-care practitioners with the expected values for binocular acuity in children with Down’s syndrome and demonstrates the visual disadvantage that children with Down’s syndrome have when compared with their typically developing peers. The results emphasise the responsibility that practitioners have to notify parents and educators of the relatively poor vision of children with Down’s syndrome, and the need for classroom modifications.

TÍTULO / TITLE:   - Changes in refractive characteristics in Japanese children with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Jpn J Ophthalmol. 2018 Mar;62(2):231-236. doi: 10.1007/s10384-018-0565-x. Epub 2018 Jan 30.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10384-018-0565-x

AUTORES / AUTHORS: - Horio J;Kaneko H; et al.

INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan 

RESUMEN / SUMMARY: - To investigate the refractive characteristics of Japanese children with Down syndrome. STUDY DESIGN: Retrospective study. METHODS: The clinical records of refractive errors and ocular manifestations in children with Down syndrome who visited the Aichi Children’s Health and Medical Center between November 2001 and January 2016 were retrospectively reviewed. The children were divided into the 3 following groups depending on their age: group 1 (

Orthopedics - Ortopedía

TÍTULO / TITLE:   - Mid-Term Results of Periacetabular Osteotomy for the Treatment of Hip Dysplasia Associated with Down Syndrome: Minimum Follow-up of Five Years.

Enlace al Resumen

REVISTA / JOURNAL:    - J Bone Joint Surg Am. 2018 Mar 7;100(5):428-434. doi: 10.2106/JBJS.17.00957.

Enlace a la Editora de la Revista http://dx.doi.org/10.2106/JBJS.17.00957

AUTORES / AUTHORS: - Maranho DA; et al

INSTITUCIÓN / INSTITUTION: - Department of Orthopedic Surgery (D.A.M., M.B.M., Y.-J.K., and E.N.N.) and Clinical Research Center (K.A.W.), Boston Children’s Hospital, Boston, Massachusetts.; 

RESUMEN / SUMMARY: - The treatment of hip dysplasia in patients with Down syndrome is challenging. We investigated the clinical, functional, and radiographic outcomes of periacetabular osteotomy (PAO) as well as factors associated with its failure at a minimum of 5 years of follow-up. METHODS: Between 1992 and 2011, 19 patients with Down syndrome (26 hips) underwent PAO at a mean age of 16.2 +/- 4.7 years. Hip pain and function were assessed with use of the modified Harris hip score (HHS) and the Gross Motor Function Classification System (GMFCS). The criteria for PAO failure were progression of osteoarthritis with a recommendation for total hip arthroplasty or hip arthrodesis, or an HHS of <60 points. Preoperative and most recent radiographs were assessed for measurement of the lateral and anterior center-edge angles, Tonnis angle, extrusion index, and anterior and posterior wall indices, and for evaluation of the Tonnis grade of osteoarthritis. RESULTS: At an average follow-up of 13.1 +/- 5.2 years (range, 5.4 to 24 years), 13 (62%) of 21 hips with an HHS demonstrated good or excellent HHS results (median, 91 points; interquartile range, 65 to 96 points). Ninety-five percent of the patients were independent in ambulation. All radiographic parameters significantly improved after PAO. Eight (31%) of the 26 hips were considered to have failed the procedure. Tonnis grade-2 osteoarthritis (4 hips compared with 1 hip; p = 0.008; odds ratio [OR] = 17.00) and older patient age at the time of the procedure (19.6 +/- 6.7 compared with 14.7 +/- 2.4 years; p = 0.017; OR = 1.36 per year) were demonstrated to be factors associated with PAO failure in an analysis of hips that failed compared with those without failure at the time of latest follow-up. CONCLUSIONS: PAO improves radiographic deformity and helps to preserve independent ambulation in patients with hip dysplasia and Down syndrome. Although nearly 70% of the hips were preserved at an average of 13 years postoperatively, 1 in 3 hips met the

TÍTULO / TITLE:   - Preliminary results of an anteverting triple periacetabular osteotomy for the treatment of hip instability in Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - J Child Orthop. 2018 Feb 1;12(1):55-62. doi: 10.1302/1863-2548.12.170174.

Enlace a la Editora de la Revista http://dx.doi.org/10.1302/1863-2548.12.170174

AUTORES / AUTHORS: - Maranho DA; et al

INSTITUCIÓN / INSTITUTION: - Department of Orthopedic Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA and Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. 

RESUMEN / SUMMARY: - To investigate the outcomes of an anteverting triple periacetabular osteotomy for the treatment of hip instability in skeletally immature patients with Down syndrome. Methods: We evaluated 16 patients (21 hips) with Down syndrome and hip instability who underwent an anteverting triple periacetabular osteotomy between 2007 and 2016. There were nine females and seven males with an average age of 7.4 years SD 2.0. We assessed the level of hip pain, gait ability and clinical stability at a minimum of one year after surgery. Radiographic evaluation included pre- and postoperative lateral centre-edge angle (LCEA), Tonnis acetabular angle and extrusion index. Result: After an average follow-up of 4.1 years SD 2.6, 20 of 21 hips (95%) remained clinically stable. In all, 12 of 16 (75%) patients had a full gait without a major limp, but three patients (19%) had a persistent limp. Of the 21 procedures, one hip (5%) was considered a failure due to persistent instability. There was a mean increase of 18.3 masculine SD 15.3 masculine of the LCEA (p < 0.001); a mean decrease of 15.2 masculine SD 11.6 masculine (p< 0.001) for the Tonnis angle and the extrusion index had a mean decrease of 0.27 SD 0.20 (p < 0.001). The most common complications were minor and included nonunion of the pubis or ischium (24%) and stress fractures of the pubis and ischium (14%). Only one patient required unplanned surgery for the treatment of an infection; which was considered a major complication. Conclusion: The anteverting triple periacetabular osteotomy provided global deformity correction and achieved hip stability in 95% of the hips after a mean follow-up of 4.1 years. Level of Evidence: Therapeutic level IV.

Physiotherapy - Fisioterapia

TÍTULO / TITLE:   - Walking performance in adolescents and young adults with Down syndrome: the role of obesity and sleep problems.

Enlace al Resumen

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2018 Apr;62(4):339-348. doi: 10.1111/jir.12474. Epub 2018 Feb 27.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12474

AUTORES / AUTHORS: - Chen CJJ; Ringenbach SDR

INSTITUCIÓN / INSTITUTION: - School of Nutrition and Health Promotion, Program of Exercise Science and Health Promotion, Arizona State University, Phoenix, AZ, USA. 

RESUMEN / SUMMARY: - High prevalence of obesity and features of obstructive sleep apnea (OSA) are major health issues in individuals with Down syndrome (DS), and both may also affect adversely on their daily activities. Further, lower levels of physical work capacity (PWC) have been reported in this population compared to their peers with intellectual disabilities. However, no study examines the relationships between obesity and sleep problems with PWC in individuals with DS. Thus, this study investigated the influence of body mass index (BMI) and different types of sleep problems on PWC in adolescents and young adults with DS (14-31 years). METHODS: The incremental treadmill walking trial was used to assess PWC. RESULTS: The negative associations were indicated between BMI and walking steps (p = .03) as well as features with OSA and walking steps (p = .04). Thus, BMI and OSA were included in the regression analysis to estimate the walking steps achieved during walking trials. In addition, Bland-Altman plots demonstrated no overestimation and underestimation of variability in the difference between actual and estimated walking steps developed by using BMI and OSA. CONCLUSIONS: Obesity and sleep problem are potentially detrimental to walking performance (i.e., fewer walking steps) in individuals with DS. Thus, individuals with DS may adopt a slow walk speed due to the increased balance deficits and physical fatigue that result from obesity and sleep fragmentation, respectively. Exercise interventions, which have the potential to reduce obesity and OSA, are recommended to improve the accomplishment of PWC in individuals with DS.

TÍTULO / TITLE:   - Factors affecting participation in physical activities in Saudi children with Down syndrome: mothers’ perspectives.

Enlace al Resumen

REVISTA / JOURNAL:    - Disabil Rehabil. 2018 Jan 30:1-12. doi: 10.1080/09638288.2018.1433241.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/09638288.2018.1433241

AUTORES / AUTHORS: - Alwhaibi RM; Aldugahishem HM

INSTITUCIÓN / INSTITUTION: - Rehabilitation Department , College of Health and Rehabilitation Sciences, Princess Nourah University , Riyadh , Saudi Arabia. 

RESUMEN / SUMMARY: - Physical activity provides a wide range of benefits. Several studies conducted in various countries have examined factors influencing participation in physical activities in children with Down syndrome. This study aimed to explore factors affecting participation in physical activities in Saudi children with DS, from their mothers’ perspectives. MATERIALS AND METHODS: In-depth interviews were conducted with 36 mothers of children with Down syndrome to explore facilitators of and barriers to their children’s participation in physical activities. All audio recordings were transcribed, validated, reviewed by the authors independently, and organized into themes. RESULTS: Transcript analysis resulted in four facilitators (mother’s support and siblings’ involvement, involvement of peers, type of physical activity experience, and child’s physical ability, behavioral, and psychological status), and six barriers (conditions associated with Down syndrome, family responsibility, social barriers, environmental constraints, electronic devices, and mother’s personal psychological barriers). CONCLUSIONS: The results regarding perceived barriers indicated a need to develop and implement programs involving family consultation. Environmental modifications should be made to accommodate the needs of children with Down syndrome. A well-organized partnership should be established and activated between private investors and the Ministries of Education, Social Affairs, and Health, to support the promotion of physical activity. Implications for rehabilitation The efficacy of home- and Internet-based programs for Saudi children with Down syndrome (DS) should be evaluated. Cultural and climactic conditions in Saudi Arabia suggest the need for environmental modifications to help children with DS engage in physical activity. Well-organized partnerships between private investors and the Ministries of Education, Social Affairs, and Health may be required to achieve higher participation of children

TÍTULO / TITLE:   - Can early physical therapy positively affect the onset of independent walking in infants with Down syndrome? A retrospective cohort study.

Enlace al Resumen

REVISTA / JOURNAL:    - Minerva Pediatr. 2018 Feb 19. pii: S0026-4946.18.05041-7. doi: 10.23736/S0026-4946.18.05041-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.23736/S0026-4946.18.05041-7

AUTORES / AUTHORS: - Corrado B; et al.

INSTITUCIÓN / INSTITUTION: - U.O.S.D. Fisiochinesiterapia, A.O.U. Policlinico Federico II, Naples, Italy  

RESUMEN / SUMMARY: - The development of both gross and fine motor skills in a child with Down syndrome is generally delayed. The most seriously affected stage is the achievement of independent walking ability, which influences the onset of all following motor and cognityive skills. The study objectives were (a) to assess the time taken to achieve independent walking ability in a cohort of children with Down syndrome, (b) to examine differences in walking onset by patient characteristics, (c) to verify the effect of early physical therapy (Neurodevelopmental Treatment on the basis of Bobath Concept practised within the first months of life) in the achievement of that skill. METHODS: A retrospective study was carried out on a cohort of 86 children with Down Syndrome. The knowledge of the exact age of walking onset and information about comorobities and rehabilitation practised since birth were the eligibility criteria. RESULTS: The average age at which walking began in the sample was 26 months (Standard Deviation = 9.66). Some patient characteristics proved to be related negatively to the walking onset: gender male, trisomy 21, improved joint ligamentous laxity. When practised, early physical therapy was able to contrast the delay in walking. CONCLUSIONS: NDT-Bobath is a well-known and valid instrument for a child with Down syndrome to attain his highest possible psychomotor functioning level. This study pointed out for the first time ever its capability to contrast the delay on walking onset, which can influences positively the development of the following motor and cognitive skills.

TÍTULO / TITLE:   - Changes in cognitive function after a 12-week exercise intervention in adults with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Disabil Health J. 2018 Feb 26. pii: S1936-6574(18)30038-4. doi: 10.1016/j.dhjo.2018.02.003.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.dhjo.2018.02.003

AUTORES / AUTHORS: - Ptomey LT; et al

INSTITUCIÓN / INSTITUTION: - Cardiovascular Research Institute, Division of Internal Medicine, The University of Kansas Medical Center, Kansas City, KS, 66160, USA. 

RESUMEN / SUMMARY: - Between 250,000 and 400,000 individuals in the United States are diagnosed with Down syndrome (DS). Nearly all adults with DS will develop Alzheimer’s disease pathology starting in their thirties. Recent studies suggest that increased physical activity (PA) may be important for maintaining components of cognition, including memory. OBJECTIVE: The purpose of this study was to evaluate changes in cognitive function after completion of a 12-week exercise intervention in adults with DS. METHODS: Participants were randomized to attend 30-minute group exercise sessions 1 or 2 times a week for 12 weeks. The exercise sessions were delivered via video conferencing on a tablet computer to groups of 5-8 participants. Sessions consisted of aerobic based exercises such as walking and jogging to music, dancing, as well as strength based exercises such as vertical jumps, bicep curls, and squats. Cognitive function was measured at baseline and end of study using the Cantab Dementia Battery for iPads, which assessed the cognitive domains of memory, attention, and reaction time. RESULTS: Twenty-seven participants (27.9+/-7.1 years of age, 40.7% female) enrolled and completed the 12-week intervention. Participants randomized to 1 session/week averaged 26.6+/-3.0min/week of PA from the group exercise session. Participants randomized to 2 sessions/week averaged 57.7+/-15.3min/week of PA from the group exercise sessions. Participants improved their performance on the two memory variables (p=0.048 and p=0.069). CONCLUSION: Increased exercise may have positive changes on memory and other cognitive functions.

TÍTULO / TITLE:   - Oxygen uptake efficiency slope during exercise in adults with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2018 Mar 24. doi: 10.1111/jar.12449.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12449

AUTORES / AUTHORS: - Mendonca GV et al

INSTITUCIÓN / INSTITUTION: - Laboratory of Motor Behavior, Faculdade de Motricidade Humana, Universidade de Lisboa, Portugal, Lisbon, Portugal. 

RESUMEN / SUMMARY: - Persons with Down syndrome (DS) have low aerobic exercise capacity. The present authors sought to compare the oxygen uptake efficiency slope (OUES) between adults with and without DS performing graded exercise testing (GXT) and to investigate its relationship with peak oxygen uptake (VO2peak ) in both groups of participants. METHOD: Twenty-three participants with DS and 24 non-disabled controls performed GXT with VO2 measurements. OUES was calculated from data of the first 75%, 90% and 100% GXT time. Multiple linear regression analyses were computed to explore associations between the independent (OUES and DS) and the dependent variables (VO2peak ). RESULTS: VO2peak , GXT time and OUES were lower in participants with DS (p < .05). OUES and DS explained 69.3% of the variance in VO2peak . CONCLUSIONS: Our findings show that OUES values are lower in persons with DS. Additionally, it was shown that OUES has predictive value for VO2peak estimations in DS.

TÍTULO / TITLE:   - Muscle stem cell dysfunction impairs muscle regeneration in a mouse model of Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Sci Rep. 2018 Mar 9;8(1):4309. doi: 10.1038/s41598-018-22342-5.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-018-22342-5

AUTORES / AUTHORS: - Pawlikowski B; et al...Olwin BB

INSTITUCIÓN / INSTITUTION: - Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO, 80309, United States 

RESUMEN / SUMMARY: - Down syndrome, caused by trisomy 21, is characterized by a variety of medical conditions including intellectual impairments, cardiovascular defects, blood cell disorders and pre-mature aging phenotypes. Several somatic stem cell populations are dysfunctional in Down syndrome and their deficiencies may contribute to multiple Down syndrome phenotypes. Down syndrome is associated with muscle weakness but skeletal muscle stem cells or satellite cells in Down syndrome have not been investigated. We find that a failure in satellite cell expansion impairs muscle regeneration in the Ts65Dn mouse model of Down syndrome. Ts65Dn satellite cells accumulate DNA damage and over express Usp16, a histone de-ubiquitinating enzyme that regulates the DNA damage response. Impairment of satellite cell function, which further declines as Ts65Dn mice age, underscores stem cell deficiencies as an important contributor to Down syndrome pathologies.

TÍTULO / TITLE:   - Using computational support in motor ability analysis of individuals with Down syndrome: Literature review.

Enlace al Resumen

REVISTA / JOURNAL:    - Comput Methods Programs Biomed. 2018 Apr;157:145-152. doi: 10.1016/j.cmpb.2018.01.029. Epub 2018 Jan

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.cmpb.2018.01.029

AUTORES / AUTHORS: - Siebra CA; Siebra HA

INSTITUCIÓN / INSTITUTION: - Health Science Faculty and Informatics Faculty, Federal University of Paraiba, Joao Pessoa, PB 58058-600 Brazil. 

RESUMEN / SUMMARY: - The lack of motor ability is one of the main Down syndrome (DS) effects. However, there are several types of motor disorders that can be attenuated or corrected if they are early identified and properly analyzed. OBJECTIVES: The aim of our study is to support the local Physical Activity research group, which works with about 25 DS children, by means of computational resources for motor analysis. To that end, we first needed to identify the main computational approaches that support the motor analysis of DS individuals, if they are already connected to intervention programs, and potential opportunities to extend the current state of the art. METHOD: We carried out a systematic review that identified 28 papers from the current literature. These papers were then analyzed to answer the research questions defined in our study. RESULTS: Our main findings were: (1) the temporal distribution of papers shows this area is new and it is starting to create a body of knowledge that in fact supports motor treatments of DS individuals; (2) there is a diversity of studies that consider different research directions such as comparisons of motor features of DS with non-DS individuals, characterization of DS motor features, and approaches for intervention programs to improve DS motor abilities; (3) there are several types of sensing hardware that enables the development of studies from different perspectives; (4) spatial monitoring is performed but only in laboratory conditions; (5); mathematical tools are largely used while strategies based on artificial intelligence for automated analysis are ignored; and (6) proposals for DS post-intervention monitoring are not found in the literature. CONCLUSION: DS motor analysis is still a new research area and it is not mature yet. Thus, the use of computational resources is very pragmatic and focused only on mathematical tools that support the numerical analysis of the acquired data. The main proposals for motor analysis are performed in labor

Prenatal diagnosis - Diagnóstico

TÍTULO / TITLE:   - Have we done our last amniocentesis? Updates on cell-free DNA for Down syndrome screening.

Enlace al Resumen

REVISTA / JOURNAL:    - ediatr Radiol. 2018 Apr;48(4):461-470. doi: 10.1007/s00247-017-3958-y. Epub 2018 Mar 17.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s00247-017-3958-y

AUTORES / AUTHORS: - Gray KJ; Wilkins-Haug LE;

INSTITUCIÓN / INSTITUTION: - Division of Maternal-Fetal Medicine, Brigham & Women’s Hospital, 75 Francis St., Boston, MA, 02115, USA 

RESUMEN / SUMMARY: - Prenatal aneuploidy screening changed significantly in 2012 when cell-free fetal deoxyribonucleic acid (DNA) was introduced as a noninvasive prenatal test. A noninvasive prenatal test detects cell free fragments of fetal DNA from the placenta circulating in maternal blood that coexist with cell-free DNA (cfDNA) of maternal origin. Using next-generation sequencing, the noninvasive prenatal test compares maternal and fetal cfDNA ratios for chromosomes of interest (i.e., 21, 18, 13, X, and Y) to assess chromosomal aneuploidy. Compared to traditional screening using ultrasound and serum markers, the noninvasive prenatal test has superior test characteristics, including a higher detection rate and positive predictive value, and a lower false-positive rate. The noninvasive prenatal test is already used for primary screening in high-risk women and is rapidly expanding to all women. Given its increasing use, understanding the noninvasive prenatal test’s limitations is critical. Discordant results (i.e. noninvasive prenatal test is positive for aneuploidy with a normal fetal karyotype) can occur because of biological processes such as aneuploidy confined to the placenta, a vanished twin, maternal aneuploidy or maternal cancer. Use of the noninvasive prenatal test for screening beyond the most common aneuploidies is not recommended. The noninvasive prenatal test is a major advance in prenatal aneuploidy screening but it is not diagnostic and does not replace invasive testing (i.e. chorionic villous sampling or amniocentesis) for confirmation of fetal chromosomal disorders.

TÍTULO / TITLE:   - Talking Points: Women’s Information Needs for Informed Decision-Making About Noninvasive Prenatal Testing for Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - J Genet Couns. 2018 Mar 17. pii: 10.1007/s10897-018-0250-8. doi: 10.1007/s10897-018-0250-8.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10897-018-0250-8

AUTORES / AUTHORS: - Dane AC; ... Miller YD;

INSTITUCIÓN / INSTITUTION: - School of Public Health and Social Work, Queensland University of Technology, Victoria Park Road, Kelvin Grove, QLD, 4059, Australia 

RESUMEN / SUMMARY: - Adequate knowledge is a vital component of informed decision-making; however, we do not know what information women value when making decisions about noninvasive prenatal testing (NIPT). The current study aimed to identify women’s information needs for decision-making about NIPT as a first-tier, non-contingent test with out-of-pocket expense and, in turn, inform best practice by specifying the information that should be prioritized when providing pre-test counseling to women in a time-limited scenario or space-limited decision support tool. We asked women (N = 242) in Australia to indicate the importance of knowing 24 information items when making a decision about NIPT and to choose two information items they would most value. Our findings suggest that women value having complete information when making decisions about NIPT. Information about the accuracy of NIPT and the pros and cons of NIPT compared to other screening and invasive tests were perceived to be most important. The findings of this study can be used to maximize the usefulness of time-limited discussions or space-limited decision support tools, but should not be routinely relied upon as a replacement for provision of full and tailored information when feasible.

TÍTULO / TITLE:   - Down’s Syndrome Screening and Reproductive Politics: Care, Choice, and Disability in the Prenatal Clinic.

Enlace al Resumen

REVISTA / JOURNAL:    - New Bioeth. 2018 Apr;24(1):95-97. doi: 10.1080/20502877.2018.1440723. Epub 2018 Feb 21.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/20502877.2018.1440723

AUTORES / AUTHORS: - Rodger D;

INSTITUCIÓN / INSTITUTION: - London South Bank University , London , UK. 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study.

Enlace al Resumen

REVISTA / JOURNAL:    - Genet Med. 2018 Mar 1. pii: gim20184. doi: 10.1038/gim.2018.4.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/gim.2018.4

AUTORES / AUTHORS: - Costa JM; et al

INSTITUCIÓN / INSTITUTION: - Laboratoire CERBA, Saint-Ouen l’Aumone, France. 

RESUMEN / SUMMARY: - PurposeCell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP).MethodsA prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322).ResultsOverall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed.ConclusioncfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.GENETICS in MEDICINE advance online publication, 1 March 2018; doi:10.1038/gim.2018.4.

TÍTULO / TITLE:   - Self-perceptions from people with Down syndrome in Japan.

Enlace al Resumen

REVISTA / JOURNAL:    - J Hum Genet. 2018 Feb 15. pii: 10.1038/s10038-018-0412-4. doi: 10.1038/s10038-018-0412-4.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s10038-018-0412-4

AUTORES / AUTHORS: - Wakai M;

INSTITUCIÓN / INSTITUTION: - Department of Genetic Counseling, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan. 

RESUMEN / SUMMARY: - Self-perception of people with Down Syndrome (DS) was originally studied in the United States in 2011; this study indicated that 99% of people with DS are happy with their lives. In this study, we investigated self-perceptions of people with DS in Japan and compared the results to the previous study made in the United States. The participants (n = 300) were 12 years old or older and members of Japan Down Syndrome Society (JDS). The questionnaire was collected between 30 October 2015 and 26 November 2015. Of 96(32%) responses, 76 (97%) agreed they are happy with their lives. We found that most people with DS in Japan also feel positive about themselves and their lives. Along with the start of Non-Invasive Prenatal Testing in Japan, DS draws an attention from Japanese people because maternal age has been increasing. This has resulted in the growth of the number of prenatal tests marketed in Japan. Therefore, we expect our results to be relevant to genetic counseling for the couples considering prenatal tests or parents raising their children with DS so that they have a clearer image about life with DS and can better visualize their life plans.

TÍTULO / TITLE:   - Importance of the integrated test in the Down’s syndrome screening algorithm.

Enlace al Resumen

REVISTA / JOURNAL:    - J Med Screen. 2018 Jan 1:969141317752533. doi: 10.1177/0969141317752533.

Enlace a la Editora de la Revista

AUTORES / AUTHORS: - Springer D et al.

INSTITUCIÓN / INSTITUTION: - Prediko Centre for Foetal Medicine, Zlin, Czech Republic Second Faculty of Medicine, Department of Clinical Biochemistry and Pathology, Charles University, Prague, Czech Republic. 

RESUMEN / SUMMARY: - Objective In the Czech Republic, over 97% of all pregnant women undergo some type of antenatal screening for Down’s syndrome. In about 95% of cases with a confirmed fetal chromosomal abnormality, the pregnancy is terminated. The most commonly used test is the first trimester combined test. We investigated the impact of implementing an integrated sequential test to improve the detection of Down’s syndrome pregnancies. Methods Data on the incidence of congenital defects, number of births, and affected pregnancies terminated are recorded in the National Registry of Congenital Anomalies. Anonymous data on cases of Down’s syndrome diagnosed antenatally or postnatally between 2010 and 2015 in one of the large antenatal care centers were analyzed. Results There were 600 diagnoses of Down’s syndrome (5.7 per 1000 births), 90% of which were made antenatally. Of antenatally detected cases, 80% were indicated for diagnostic procedure by multimarker screening results. In the multimarker screen positive group, 75% cases were first trimester positive and 25% second trimester positive (most of these had positive integrated test results). Among Down’s syndrome cases indicated for antenatal diagnosis by multimarker screening results 6.25% (n = 26) were first trimester negative, and became positive after integration with the second trimester screening results. Conclusions Results from five major Czech antenatal centers confirm that an integrated sequential test would detect 80-85% of Down’s syndrome fetuses in the first trimester and at least an extra 5-10% of Down’s syndrome pregnancies in the second trimester of pregnancy. These are important data that should be considered in implementing the national antenatal screening program.

TÍTULO / TITLE:   - Late-onset fetal bilateral pleural effusions associated with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Taiwan J Obstet Gynecol. 2018 Feb;57(1):133-136. doi: 10.1016/j.tjog.2018.01.001.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.tjog.2018.01.001

AUTORES / AUTHORS: - Lai ST; et al.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - We present two cases of late-onset bilateral fetal pleural effusions associated with fetal Down syndrome. CASE REPORTS: Case 1. A 33-year-old Vietnamese woman had undergone regular sonographic examinations since 23 weeks of gestation and no abnormality had been noted. However, bilateral moderate pleural effusions were found at 33 weeks of gestation, and massive pleural effusion, ascites and polyhydramnios developed at 34 weeks of gestation. Aspiration of the pleural effusion was subsequently performed. Clinical laboratory surveys of the aspiration fluid excluded toxoplasmosis and cytomegalovirus infection. Cytogenetic analysis of cultured lymphocytes derived from pleural effusion revealed a karyotype of 47,XX,+21. The parents elected to continue the pregnancy. Intrauterine fetal demise occurred at 37 weeks of gestation, and a macerated female baby was delivered. Postnatal cytogenetic analysis of the umbilical cord confirmed the prenatal diagnosis. Case 2. A 41-year-old Pakistani woman had undergone regular sonographic examinations and no abnormality had been noted. However, isolated bilateral mild pleural effusions were noted at 27 weeks of gestation. Amniocentesis revealed a karyotype of 47,XY,+21 and simultaneous array comparative genomic hybridization analysis of uncultured amniocytes confirmed the diagnosis of Down syndrome. The pregnancy was subsequently terminated. CONCLUSION: Fetuses with Down syndrome may present late-onset bilateral pleural effusions. Prenatal diagnosis of late-onset bilateral pleural effusions should raise the possibility of fetal Down syndrome and cytogenetic investigation is warranted.

Psychiatry - Psiquiatría

TÍTULO / TITLE:   - : Aripiprazole Treatment of Compulsive Behaviors Associated With Methylphenidate in a Child With Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - J Clin Psychopharmacol. 2018 Apr;38(2):159-161. doi: 10.1097/JCP.0000000000000839.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/JCP.0000000000000839

AUTORES / AUTHORS: - Sertdemir M;

INSTITUCIÓN / INSTITUTION: - Department of Child and Adolescent Psychiatry, Meram School of Medicine, Necmettin Erbakan University, Konya, Turkey 

RESUMEN / SUMMARY: -

Quality of life - Calidad de vida

TÍTULO / TITLE:   - Disparities in Access to Healthcare Transition Services for Adolescents with Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - J Pediatr. 2018 Mar 20. pii: S0022-3476(18)30160-4. doi: 10.1016/j.jpeds.2018.01.072.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jpeds.2018.01.072

AUTORES / AUTHORS: - Nugent J; et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Joint Base Langley-Eustis, Hampton, VA; Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 

RESUMEN / SUMMARY: - To compare healthcare transition planning in adolescents with Down syndrome with adolescents with other special healthcare needs. STUDY DESIGN: Data were drawn from the 2009-2010 National Survey of Children with Special Health Care Needs, a nationally representative sample with 17 114 adolescents aged 12-17 years. Parents were asked whether providers and the study child had discussed shifting to an adult provider, changing healthcare needs, maintaining health insurance coverage, and taking responsibility for self-care. The transition core outcome was a composite measure based on the results of these 4 questions. Multivariable logistic regression determined the association between Down syndrome and the transition core outcome as well as each of the 4 individual component measures. RESULTS: Although 40% of adolescents with other special healthcare needs met the transition core outcome, 11.0% of adolescents with Down syndrome met this outcome. Adolescents with Down syndrome were less likely to be encouraged to take responsibility for their health (32.2% vs 78.4%). After adjustment for demographic, socioeconomic, and health-related factors, adolescents with Down syndrome had 4 times the odds of not meeting the transition core outcome. For the component measures, Down syndrome adolescents had 4 times the odds of not being encouraged to take responsibility for self-care. Medical home access increased the odds of transition preparation. CONCLUSIONS: Adolescents with Down syndrome experience disparities in access to transition services. Provider goals for adolescents with Down syndrome should encourage as much independence as possible in their personal care and social lives.

TÍTULO / TITLE:   - Prevalence of physical conditions and multimorbidity in a cohort of adults with intellectual disabilities with and without Down syndrome: cross-sectional study.

Enlace al Resumen

REVISTA / JOURNAL:    - Bibliographic Citation British Medical J. (BMJ): <> Open. 2018 Feb 5;8(2). http://bmj.com/search.dtl

Enlace a la Editora de la Revista http://dx.doi.org/10.1136/bmjopen-2017-018292

AUTORES / AUTHORS: - Kinnear D; et al.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - To investigate the prevalence of multimorbidity in adults with intellectual disabilities with and without Down syndrome. DESIGN: Large, population-based cross-sectional study. SETTING: The geographical area of one Health Board, Scotland. PARTICIPANTS: All adults (aged 16+ years) known to general practitioners to have intellectual disabilities and adults receiving services provided or paid by intellectual disabilities health or social work services. 1023/1562 potential participants took part (65.5%); 562 (54.9%) men and 461 (45.1%) women, aged 43.9 years (16-83 years). 186 had Down syndrome and 837 did not. MAIN OUTCOME MEASURES: The prevalence of International Statistical Classification of Diseases, 10th revision, physical health conditions and multimorbidity detected at a comprehensive health assessment. RESULTS: The mean number of physical health conditions/participant was 11.04, and 98.7% had multimorbidity. The most prevalent conditions are painful and/or disabling and, in some cases, life threatening. The five most prevalent were visual impairment, obesity, epilepsy, constipation and ataxic/gait disorders. The pattern of multimorbidity differs from that seen in the general population and is spread across the entire adult life course. The extent of multimorbidity in the adults with Down syndrome was similar to that of the adults without Down syndrome, while the prevalence of individual conditions differed. CONCLUSIONS: This robustly designed study with a large population found an extremely high prevalence of multimorbidity in adults with intellectual disabilities across the entire adult life course. This increases complexity of medical management that secondary healthcare services and medical education are not yet geared towards, as these tend to focus on single conditions. This is in addition to complexity due to limitations in communication and understanding. As the physical conditions within their multimorbidity also differ from that seen in the older general

TÍTULO / TITLE:   - What factors influence recruitment to a birth cohort of infants with Down’s syndrome?

Enlace al Resumen

REVISTA / JOURNAL:    - Arch Dis Child. 2018 Mar 8. pii: archdischild-2017-314312. doi: 10.1136/archdischild-2017-314312.

Enlace a la Editora de la Revista http://dx.doi.org/10.1136/archdischild-2017-314312

AUTORES / AUTHORS: - Williams GM; et al.

INSTITUCIÓN / INSTITUTION: - The NIHR Bristol Biomedical Research Centre, Nutrition Theme, University of Bristol, Bristol, UK.; 

RESUMEN / SUMMARY: - To understand how to maximise recruitment of young infants with Down’s syndrome (DS) into research through qualitative interviews with parents and care providers. In complex neonatal and genetic conditions such as DS, frequently diagnosed after birth, parents may go through a period of adaptation. These factors need consideration when overcoming barriers to recruitment. PARTICIPANTS AND DESIGN: Participants, who were drawn from health professionals and volunteers working with families experiencing DS, were recruited using a purposive sampling strategy. Semistructured telephone interviews were completed with nine paediatricians, three research nurses and six family support workers. Five of those interviewed had a child with DS. The interviews were transcribed and analysed thematically. RESULTS: A positive decision to take part in a ‘from-birth’ cohort study depends on factors such as the child’s overall health, parent demographics (educational background and ethnicity), medical interactions that take place with the families (communication) and study logistics. The data suggest that recruitment methods need to take all these factors into consideration. Multiple recruitment methods should be considered including face to face, through parent and support groups, websites and social media. There also needs to be flexibility in the research timings to fit around the needs of the child and parents. CONCLUSION: Researchers need to be aware of the variable responses elicited by families to a diagnosis of DS for their baby and be sensitive to the child’s current medical status. This does not preclude recruitment into studies, but to maximise uptake good communication and flexibility is essential.

TÍTULO / TITLE:   - 50 years with Down syndrome: A longitudinal study.

Enlace al Resumen

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2018 Mar 2. doi: 10.1111/jar.12438.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12438

AUTORES / AUTHORS: - Carr J; Collins S

INSTITUCIÓN / INSTITUTION: - Tizard Centre, University of Kent, Canterbury, UK. Faculty of Social Sciences, University of Essex, Colchester, UK. 

RESUMEN / SUMMARY: - A population sample of people with Down syndrome, studied from infancy, has now been followed up at the age of 50 years. From the original sample of 54, there were 27 still in the study at the age of 50, all but four of the losses resulting from deaths. METHODS: Intelligence and language skills were tested and daily living skills assessed. Memory/cognitive deterioration was examined using two test instruments. Other aspects of the people’s lives were examined via carers’ reports. RESULTS: Scores on verbal tests showed little change. Those on a non-verbal test, on self-help skills and on both memory tests showed some decline, even when the scores of those already suffering from dementia were discounted. CONCLUSIONS: At the age of 50, those not already diagnosed with dementia showed some decline on most tests. While this may include scores of people who subsequently develop dementia, it may also reflect the normal ageing process in this population.

TÍTULO / TITLE:   - Quality of life in Down syndrome: a matter of perspective.

Enlace al Resumen

REVISTA / JOURNAL:    - Dev Med Child Neurol. 2018 Apr;60(4):337-338. doi: 10.1111/dmcn.13706. Epub 2018 Feb 14.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/dmcn.13706

AUTORES / AUTHORS: - Newton R

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Self-perceptions from people with Down syndrome in Japan.

Enlace al Resumen

REVISTA / JOURNAL:    - J Hum Genet. 2018 Feb 15. pii: 10.1038/s10038-018-0412-4. doi: 10.1038/s10038-018-0412-4.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s10038-018-0412-4

AUTORES / AUTHORS: - Wakai M;

INSTITUCIÓN / INSTITUTION: - Department of Genetic Counseling, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan. 

RESUMEN / SUMMARY: - Self-perception of people with Down Syndrome (DS) was originally studied in the United States in 2011; this study indicated that 99% of people with DS are happy with their lives. In this study, we investigated self-perceptions of people with DS in Japan and compared the results to the previous study made in the United States. The participants (n = 300) were 12 years old or older and members of Japan Down Syndrome Society (JDS). The questionnaire was collected between 30 October 2015 and 26 November 2015. Of 96(32%) responses, 76 (97%) agreed they are happy with their lives. We found that most people with DS in Japan also feel positive about themselves and their lives. Along with the start of Non-Invasive Prenatal Testing in Japan, DS draws an attention from Japanese people because maternal age has been increasing. This has resulted in the growth of the number of prenatal tests marketed in Japan. Therefore, we expect our results to be relevant to genetic counseling for the couples considering prenatal tests or parents raising their children with DS so that they have a clearer image about life with DS and can better visualize their life plans.

TÍTULO / TITLE:   - Early death and causes of death of people with Down syndrome: A systematic review.

Enlace al Resumen

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2018 Mar 24. doi: 10.1111/jar.12446.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12446

AUTORES / AUTHORS: - OLeary L et al.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - It is thought that people with Down syndrome die younger than the general population, but that survival rates are improving. METHODS: Five databases were searched for keywords related to intellectual disabilities, Down syndrome and mortality. Strict inclusion criteria were applied. Information from 34 selected studies was tabulated, extracted and synthesized. RESULTS: People with Down syndrome died about 28 years younger than the general population. Congenital heart anomalies, comorbidities, low birthweight, and Black and minority ethnicity influenced earlier age of death, as did younger maternal age and poorer parental education. Congenital heart anomalies and respiratory conditions were the leading causes of death, and more common than in the general population. Survival rates have improved over time, particularly for those with congenital heart anomalies. CONCLUSIONS: People with Down syndrome are living longer but still die younger of different causes than the general population. More robust comparative data are needed, and ethnic differences require further study.

TÍTULO / TITLE:   - Adaptive behavior in infants and toddlers with Down syndrome and fragile X syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Am J Med Genet B Neuropsychiatr Genet. 2018 Apr;177(3):358-368. doi: 10.1002/ajmg.b.32619. Epub 2018

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.b.32619

AUTORES / AUTHORS: - Will EA

INSTITUCIÓN / INSTITUTION: - Department of Psychology, University of South Carolina, Columbia, South Carolina. 

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) experience deficits across all domains of adaptive functioning, however little is known about the emergence and age-related changes of these impairments compared to other neurogenetic disorders with similar intellectual disability impairments, such as fragile X syndrome (FXS). Adaptive behavior is key for optimal functioning in these populations. Participants aged 5-45 months comprised three age-matched groups, DS (n = 64), FXS (n = 69), and typically developing controls (TD; n = 69). Adaptive behavior was measured on the Vineland Adaptive Behavior Scales-II. Regressions were used to examine adaptive behavior in a cross-sectional design across age. DS infants and toddlers evidenced deficits across all areas of adaptive behaviors compared to the age-matched TD group, with clear impairments present in the first year of life. Motor skills were the area of greatest weakness in children with DS with significant impairment evident at 12 months of age that remained low through 3 years. Compared to age-matched children with FXS, children with DS showed initially lower standard scores at 12 months of age, but slower declines in standard scores across age, resulting in less impaired functioning at 36 months. This is the first study to compare adaptive behavior in infants and toddlers with DS to FXS, and demonstrate the phenotypic specificity of adaptive profiles in this diagnostic group. These findings provide evidence that adaptive behavior should be a major target of intervention in children with FXS and DS, and that these differences are potentially driven by unique etiologies attributable to each disorder.

Respiratory - Respiratorio

TÍTULO / TITLE:   - Lingual tonsillectomy in children with Down syndrome: Is it safe?

Enlace al Resumen

REVISTA / JOURNAL:    - Int J Pediatr Otorhinolaryngol. 2018 Feb;105:52-55. doi: 10.1016/j.ijporl.2017.11.027. Epub 2017 N

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ijporl.2017.11.027

AUTORES / AUTHORS: - Skirko JR;

INSTITUCIÓN / INSTITUTION: - Division of Pediatric Otolaryngology-Head & Neck Surgery, University of Utah and Primary Children’s Hospital, United States.  

RESUMEN / SUMMARY: - Evaluate peri-operative course and morbidity in children with Down syndrome (DS) who underwent a lingual tonsillectomy (LT) for residual obstructive sleep apnea (rOSA). METHODS: Retrospective case series for children with DS who underwent LT for rOSA from April 2011 to July 2016. Our primary outcomes were length of stay, readmission and complications. Surgical effectiveness was evaluated by change in the obstructive apnea-hypopnea-index(OAHI) and oxygen saturation nadir. RESULTS: Thirty-nine patients underwent LT. The mean length of stay was 1.3 days with n = 21(72%) staying one night. One subject (2.6%) had a post-operative bleed that did not require operative intervention. No other major complications occurred. In terms of effectiveness of surgery, twenty-nine children had sufficient data for inclusion. Median OAHI did not appreciably change (p = 0.07) from before surgery. Five subjects (17%) were cured of OSA (OAHI < 2/hour) and a mix of improvement and worsening was identified. The lowest oxygen saturation improved from 78% (SD = 7) before surgery to 82% (SD = 6) after surgery (p = 0.003). CONCLUSION: LT has a favorable post-operative course but its effectiveness at curing rOSA in the DS population has not been established/proven. Further research is indicated to determine optimal surgical management for DS children with LTH. 

TÍTULO / TITLE:   - Is Trisomy 21 a Risk Factor for Rapid Progression of Pulmonary Arteriopathy?- Revisiting Histopathological Characteristics Using 282 Lung Biopsy Specimens.

Enlace al Resumen

REVISTA / JOURNAL:    - Circ J. 2018 Mar 16. doi: 10.1253/circj.CJ-17-0754.

Enlace a la Editora de la Revista http://dx.doi.org/10.1253/circj.CJ-17-0754

AUTORES / AUTHORS: - Masaki N; et al.

INSTITUCIÓN / INSTITUTION: - Division of Cardiovascular Surgery, Tohoku University Graduate School of Medicine. 

RESUMEN / SUMMARY: - Pulmonary hypertension (PH) is more progressive in trisomy 21 patients. However, pulmonary arteriopathic lesions in these patients have not been fully characterized histopathologically.Methods and Results:A retrospective review of a lung biopsy registry identified 282 patients: 188 patients with trisomy 21 (Group D) and 94 without (Group N). The mean age at lung biopsy was 3 and 7 months (P<0.0001). Pulmonary arterial pressure (PAP) and pulmonary vascular resistance were similar between the 2 groups. There were no significant differences in the proportion of patients with irreversible intimal lesions or the index of pulmonary vascular disease (IPVD; a measure of the degree of pulmonary arteriopathy progression) between the 2 groups. In addition, after propensity score matching for patient background (n=43 in each group), there were no significant differences in IPVD (P=0.29) or the ratio of irreversible intimal changes between the D and N groups (P=0.39). Multivariate analysis identified age (P<0.0001) and PAP (P=0.03) as the only risk factors for progression of pulmonary arteriopathy. CONCLUSIONS: Histopathologically, early progression of pulmonary arteriopathy in patients with trisomy 21 was not proved compared with patients without trisomy 21. Although we cannot exclude the possibility of bias in the Group D and N patients who were slated for lung biopsy, factors other than pulmonary arteriopathy may affect the marked progression of clinical PH in trisomy 21 patients.

TÍTULO / TITLE:   - Late-onset fetal bilateral pleural effusions associated with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Taiwan J Obstet Gynecol. 2018 Feb;57(1):133-136. doi: 10.1016/j.tjog.2018.01.001.

Enlace a la Editora de la Revista Taiwan J Obstet Gynecol. 2018 Feb;57(1):133-136. doi: 10.1016/j.tjog.2018.01.001.

AUTORES / AUTHORS: - Lai ST; et al.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - We present two cases of late-onset bilateral fetal pleural effusions associated with fetal Down syndrome. CASE REPORTS: Case 1. A 33-year-old Vietnamese woman had undergone regular sonographic examinations since 23 weeks of gestation and no abnormality had been noted. However, bilateral moderate pleural effusions were found at 33 weeks of gestation, and massive pleural effusion, ascites and polyhydramnios developed at 34 weeks of gestation. Aspiration of the pleural effusion was subsequently performed. Clinical laboratory surveys of the aspiration fluid excluded toxoplasmosis and cytomegalovirus infection. Cytogenetic analysis of cultured lymphocytes derived from pleural effusion revealed a karyotype of 47,XX,+21. The parents elected to continue the pregnancy. Intrauterine fetal demise occurred at 37 weeks of gestation, and a macerated female baby was delivered. Postnatal cytogenetic analysis of the umbilical cord confirmed the prenatal diagnosis. Case 2. A 41-year-old Pakistani woman had undergone regular sonographic examinations and no abnormality had been noted. However, isolated bilateral mild pleural effusions were noted at 27 weeks of gestation. Amniocentesis revealed a karyotype of 47,XY,+21 and simultaneous array comparative genomic hybridization analysis of uncultured amniocytes confirmed the diagnosis of Down syndrome. The pregnancy was subsequently terminated. CONCLUSION: Fetuses with Down syndrome may present late-onset bilateral pleural effusions. Prenatal diagnosis of late-onset bilateral pleural effusions should raise the possibility of fetal Down syndrome and cytogenetic investigation is warranted.

Surgery - Cirugía

TÍTULO / TITLE:   - Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery.

Enlace al Resumen

REVISTA / JOURNAL:    - Pediatr Crit Care Med. 2018 Mar 15. doi: 10.1097/PCC.0000000000001537.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/PCC.0000000000001537

AUTORES / AUTHORS: - Goot BH; et al

INSTITUCIÓN / INSTITUTION: - The Heart Institute, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado, Denver School of Medicine, Aurora, CO. 

RESUMEN / SUMMARY: - To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. DESIGN: Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. SETTING: A 16-bed cardiac ICU at an university-affiliated hospital. PATIENTS: Forty-two patients (20 Down syndrome, 22 controls) were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. CONCLUSIONS: This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.

Therapeutics - Terapéutica

TÍTULO / TITLE:   - Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery.

Enlace al Resumen

REVISTA / JOURNAL:    - Pediatr Crit Care Med. 2018 Mar 15. doi: 10.1097/PCC.0000000000001537.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/PCC.0000000000001537

AUTORES / AUTHORS: - Goot BH; et al

INSTITUCIÓN / INSTITUTION: - The Heart Institute, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado, Denver School of Medicine, Aurora, CO. 

RESUMEN / SUMMARY: - To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. DESIGN: Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. SETTING: A 16-bed cardiac ICU at an university-affiliated hospital. PATIENTS: Forty-two patients (20 Down syndrome, 22 controls) were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. CONCLUSIONS: This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.

TÍTULO / TITLE:   - DYRK1A inhibition and cognitive rescue in a Down syndrome mouse model are induced by new fluoro-DANDY derivatives.

Enlace al Resumen

REVISTA / JOURNAL:    - Sci Rep. 2018 Feb 12;8(1):2859. doi: 10.1038/s41598-018-20984-z.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-018-20984-z

AUTORES / AUTHORS: - Neumann F; et al.

INSTITUCIÓN / INSTITUTION: - Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Universite Paris-Sud, Universite Paris-Saclay, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.  

RESUMEN / SUMMARY: - Inhibition of DYRK1A kinase, produced by chromosome 21 and consequently overproduced in trisomy 21 subjects, has been suggested as a therapeutic approach to treating the cognitive deficiencies observed in Down syndrome (DS). We now report the synthesis and potent DYRK1A inhibitory activities of fluoro derivatives of 3,5-di(polyhydroxyaryl)-7-azaindoles (F-DANDYs). One of these compounds (3-(4-fluorophenyl)-5-(3,4-dihydroxyphenyl)-1H-pyrrolo[2,3-b]pyridine, 5a) was selected for in vivo studies of cognitive rescuing effects in a standard mouse model of DS (Ts65Dn line). Using the Morris water maze task, Ts65Dn mice treated i.p. with 20 mg/kg of 5a performed significantly better than Ts65Dn mice treated with placebo, confirming the promnesiant effect of 5a in the trisomic mice. Overall, these results demonstrate for the first time that selective and competitive inhibition of DYRK1A kinase by the F-DANDY derivative 5a may provide a viable treatment strategy for combating the memory and learning deficiencies encountered in DS.

Education - Educación

TÍTULO / TITLE:   - Personalized reading intervention for children with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - J Sch Psychol. 2018 Feb;66:67-84. doi: 10.1016/j.jsp.2017.07.006. Epub 2017 Sep 20

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jsp.2017.07.006

AUTORES / AUTHORS: - Lemons CJ; ... Fidler DJ

INSTITUCIÓN / INSTITUTION: - Peabody College of Vanderbilt University, United States. 

RESUMEN / SUMMARY: - The purpose of this replication study was to evaluate the potential efficacy and feasibility of an early reading intervention for children with Down syndrome. The intervention was developed in alignment with the Down syndrome behavioral phenotype. Six children between the ages of seven and ten years participated in a series of multiple-probe across lessons single-case design studies. Results indicate a functional relation between intervention and reading outcomes for four children. Results were mixed for one participant and no functional relation was demonstrated for another. The potential promise of pursuing aptitude-by-treatment interaction research for subgroups of learners with similar characteristics as an effort to personalize intervention is discussed.

TÍTULO / TITLE:   - Measuring feeding difficulties in toddlers with Down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Appetite. 2018 Mar 27;126:61-65. doi: 10.1016/j.appet.2018.03.018.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.appet.2018.03.018

AUTORES / AUTHORS: - van Dijk M; Lipke-Steenbeek W

INSTITUCIÓN / INSTITUTION: - Heymans Institute for Psychological Research, University of Groningen, Grote Kruisstraat 2/1, 9712 TS, Groningen, The Netherlands. 

RESUMEN / SUMMARY: - Early feeding problems occur frequently across the population, but have a higher incidence in children with Down syndrome (DS). Early identification can possibly be improved with the help of a valid screening instrument based on caregiver reports. In a previous study, we investigated the concurrent validity of the Dutch version of the Montreal Children’s Hospital Feeding Scale (MCH-FS, SEP in Dutch) in a sample of typically developing toddlers, and we found a correlation between the score on the instrument and observed behavior during a regular meal. The current pilot study was a replication in a sample of children with DS (aged 1; 0-3; 0) and their primary caregivers (n=32). The results showed that children in the sample did not score higher on the SEP than children in their respective norm groups. In addition, when caregivers reported more symptoms of feeding problems on the SEP, children showed more food refusal and negative affect during the observed meal. This suggests that the screening instrument is particularly associated with negative mealtime interactions. This is in contrast with earlier results, which mainly indicated a relation with eating skills.

TÍTULO / TITLE:   - Growth and Decline in Language and Phonological Memory Over Two Years Among Adolescents With Down Syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2018 Mar;123(2):103-118. doi: 10.1352/1944-7558-123.2.103.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-123.2.103

AUTORES / AUTHORS: - Conners FA; et al.

INSTITUCIÓN / INSTITUTION: - Frances A. Conners and Andrew S. Tungate, Department of Psychology, The University of Alabama. 

RESUMEN / SUMMARY: - Forty-two adolescents with Down syndrome (DS) ages 10 to 21 years completed a battery of language and phonological memory measures twice, 2 years apart. Individual differences were highly stable across two years. Receptive vocabulary scores improved, there was no change in receptive or expressive grammar scores, and nonword repetition scores declined. Digit memory and expressive vocabulary scores improved among younger adolescents, but generally held steady among older adolescents. These patterns may reveal key points in development at which interventions may be best applied. Further research is needed to understand specific processes in tasks that appear to be slowing or declining during adolescence. They may be important for understanding early aging and dementia in DS.

TÍTULO / TITLE:   - Enhancing the comprehension of visual metaphors in individuals with intellectual disability with or without down syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Res Dev Disabil. 2018 Mar;74:113-123. doi: 10.1016/j.ridd.2018.01.010. Epub 2018 Feb 3.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2018.01.010

AUTORES / AUTHORS: - Shnitzer-Meirovich S;... Mashal N

INSTITUCIÓN / INSTITUTION: - School of Education, Bar Ilan University, Ramat Gan, Israel; Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel. 

RESUMEN / SUMMARY: - This study is the first to investigate the effectiveness of deep and shallow intervention programs in the acquisition of visual metaphor comprehension in individuals with non-specific intellectual disability (NSID; aged 15-59, N=53) or Down syndrome (DS; aged 15-52, N=50). The deep intervention program was based on dynamic assessment model for enhancing analogical thinking. The shallow intervention program involves memorizing a metaphorical relationship between pairs of pictures. Visual metaphor comprehension was measured by the construction of a metaphorical connection between pairs of pictures. The results indicated that both etiology groups exhibited poor understanding of visual metaphors before the intervention. A significant improvement was observed in both interventions and both etiology groups, with greater improvement among individuals who underwent the deep processing. Moreover, the latter procedure led to greater generalization ability. The results also indicated that vocabulary contributed significantly to understanding unstudied metaphors and that participants with poorer linguistic abilities exhibited greater improvement in their metaphorical thinking. Thus, individuals with ID with or without DS are able to recruit the higher-order cognitive abilities required for visual metaphor comprehension.

TÍTULO / TITLE:   - Contributions of speech-language therapy to the integration of individuals with Down syndrome in the workplace.

Enlace al Resumen

REVISTA / JOURNAL:    - Codas. 2018 Mar 1;30(1):e20160144. doi: 10.1590/2317-1782/20172016144.

Enlace a la Editora de la Revista http://dx.doi.org/10.1590/2317-1782/20172016144

AUTORES / AUTHORS: - Barbosa TMMF; et al.

INSTITUCIÓN / INSTITUTION: - Departamento de Fonoaudiologia, Universidade Federal da Paraiba - UFPB - Joao Pessoa (PB), Brasil. 

RESUMEN / SUMMARY: - To analyze the contributions of speech-language therapy in the integration of young individuals with Down syndrome (DS) into the workplace, with reference to their professionalization. METHODS: A questionnaire was distributed to eight undergraduate students (tutors) who participated in a project with individuals with DS, five mothers of individuals with DS, and five employees from the institution in which the present study was conducted. The questionnaire assessed the communication, memory, behavior, social interaction, autonomy and independence of the participants with DS, called “trainees”. The trainees were employed in one of five routine work sectors at the university that conducted the present study. The data collected in this descriptive and cross-sectional study were analyzed quantitatively and qualitatively. The Research Ethics Committee of the affiliated institute approved the project. RESULTS: Mothers and tutors rated the trainees’ language skills as “good”. However, their ratings differed from those of the participating employees. After the trainees with DS were placed in a work environment, significant changes were observed in their communication and autonomy. There was no improvement in the trainees’ independence, but after training noticeable changes were observed in their social behavior and autonomy. CONCLUSION: Speech-language therapy during vocational training led to positive changes in the social behavior of individuals with DS, as evidenced by an increase in their autonomy and communication.

TÍTULO / TITLE:   - Adaptive behavior in infants and toddlers with Down syndrome and fragile X syndrome.

Enlace al Resumen

REVISTA / JOURNAL:    - Am J Med Genet B Neuropsychiatr Genet. 2018 Apr;177(3):358-368. doi: 10.1002/ajmg.b.32619. Epub 2018

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.b.32619

AUTORES / AUTHORS: - Will EA

INSTITUCIÓN / INSTITUTION: - Department of Psychology, University of South Carolina, Columbia, South Carolina. 

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) experience deficits across all domains of adaptive functioning, however little is known about the emergence and age-related changes of these impairments compared to other neurogenetic disorders with similar intellectual disability impairments, such as fragile X syndrome (FXS). Adaptive behavior is key for optimal functioning in these populations. Participants aged 5-45 months comprised three age-matched groups, DS (n = 64), FXS (n = 69), and typically developing controls (TD; n = 69). Adaptive behavior was measured on the Vineland Adaptive Behavior Scales-II. Regressions were used to examine adaptive behavior in a cross-sectional design across age. DS infants and toddlers evidenced deficits across all areas of adaptive behaviors compared to the age-matched TD group, with clear impairments present in the first year of life. Motor skills were the area of greatest weakness in children with DS with significant impairment evident at 12 months of age that remained low through 3 years. Compared to age-matched children with FXS, children with DS showed initially lower standard scores at 12 months of age, but slower declines in standard scores across age, resulting in less impaired functioning at 36 months. This is the first study to compare adaptive behavior in infants and toddlers with DS to FXS, and demonstrate the phenotypic specificity of adaptive profiles in this diagnostic group. These findings provide evidence that adaptive behavior should be a major target of intervention in children with FXS and DS, and that these differences are potentially driven by unique etiologies attributable to each disorder.

 Realizar busqueda