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AGING - ENVEJECIMIENTO

TÍTULO / TITLE:    - Candidate gene analysis for Alzheimer’s disease in adults with Down syndrome.

REVISTA / JOURNAL:    - Neurobiol Aging. 2017 May 3. pii: S0197-4580(17)30146-X. doi: 10.1016/j.neurobiolaging.2017.04.018.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.neurobiolaging.2017.04.018

AUTORES / AUTHORS: - Lee JH; Lee AJ; et al.

INSTITUCIÓN / INSTITUTION: - Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, School of Public Health,   JHL2@columbia.edu

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) overexpress many genes on chromosome 21 due to trisomy and have high risk of dementia due to the Alzheimer’s disease (AD) neuropathology. However, there is a wide range of phenotypic differences (e.g., age at onset of AD, amyloid beta levels) among adults with DS, suggesting the importance of factors that modify risk within this particularly vulnerable population, including genotypic variability. Previous genetic studies in the general population have identified multiple genes that are associated with AD. This study examined the contribution of polymorphisms in these genes to the risk of AD in adults with DS ranging from 30 to 78 years of age at study entry (N = 320). We used multiple logistic regressions to estimate the likelihood of AD using single-nucleotide polymorphisms (SNPs) in candidate genes, adjusting for age, sex, race/ethnicity, level of intellectual disability and APOE genotype. This study identified multiple SNPs in APP and CST3 that were associated with AD at a gene-wise level empirical p-value of 0.05, with odds ratios in the range of 1.5-2. SNPs in MARK4 were marginally associated with AD. CST3 and MARK4 may contribute to our understanding of potential mechanisms where CST3 may contribute to the amyloid pathway by inhibiting plaque formation, and MARK4 may contribute to the regulation of the transition between stable and dynamic microtubules.

TÍTULO / TITLE:    - Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome.

REVISTA / JOURNAL:    - Sci Rep. 2017 Apr 3;7:45561. doi: 10.1038/srep45561.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/srep45561

AUTORES / AUTHORS: - Kazim SF; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurochemistry, and SUNY Downstate/NYSIBR Center for Developmental Neuroscience, New York State Institute for Basic Research (NYSIBR), Staten Island, NY 10314, USA.; The Robert F. Furchgott Center for Neural and Behavioral Sc  

RESUMEN / SUMMARY: - Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3beta) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model.

TÍTULO / TITLE:    - Down syndrome: age-dependence of PiB binding in postmortem frontal cortex across the lifespan.

REVISTA / JOURNAL:    - Neurobiol Aging. 2017 Jun;54:163-169. doi: 10.1016/j.neurobiolaging.2017.03.005. Epub 2017 Mar 14.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.neurobiolaging.2017.03.005

AUTORES / AUTHORS: - LeVine H 3rd; ... and Head E;

INSTITUCIÓN / INSTITUTION: - Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.   elizabeth.head@uky.edu

RESUMEN / SUMMARY: - Beta-amyloid (Abeta) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh compound B (PiB) ligand has facilitated studies linking Abeta, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro 3H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (n = 25) and DS (n = 39). In DS, 3H-PiB binding was significantly associated with age. After age 40 years in DS, 3H-PiB binding rose dramatically along with increasing individual variability. 3H-PiB binding correlated with the amount of Abeta42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and cerebral amyloid angiopathy in DS brain.

TÍTULO / TITLE:    - Long-term effect of neonatal inhibition of APP gamma-secretase on hippocampal development in the Ts65Dn mouse model of Down syndrome.

REVISTA / JOURNAL:    - Neurobiol Dis. 2017 Jul;103:11-23. doi: 10.1016/j.nbd.2017.03.012. Epub 2017 Mar 28.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2017.03.012

AUTORES / AUTHORS: - Stagni F; ... Bartesaghi R;

INSTITUCIÓN / INSTITUTION: - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.   renata.bartesaghi@unibo.it

RESUMEN / SUMMARY: - Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed. Previous evidence showed that neonatal treatment with ELND006, an inhibitor of gamma-secretase, reinstates the Shh pathway and fully restores neurogenesis in Ts65Dn pups. In the framework of potential therapies for DS, it is extremely important to establish whether the positive effects of early intervention are retained after treatment cessation. Therefore, the goal of the current study was to establish whether early treatment with ELND006 leaves an enduring trace in the brain of Ts65Dn mice. Ts65Dn and euploid pups were treated with ELND006 in the postnatal period P3-P15 and the outcome of treatment was examined at ~one month after treatment cessation. We found that in treated Ts65Dn mice the pool of proliferating cells in the hippocampal dentate gyrus (DG) and total number of granule neurons were still restored as was the number of pre- and postsynaptic terminals in the stratum lucidum of CA3, the site of termination of the mossy fibers from the DG. Accordingly, patch-clamp recording from field CA3 showed functional normalization of the input to CA3. Unlike in field CA3, the number of pre- and postsynaptic terminals in the DG of treated Ts65Dn mice was no longer fully restored. The finding that many of the positive effects of neonatal treatment were retained after treatment cessation provides proof of principle demonstration of the efficacy of early inhibiti

TÍTULO / TITLE:    - Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline.

REVISTA / JOURNAL:    - Neurobiol Aging. 2017 Apr 18;56:41-49. doi: 10.1016/j.neurobiolaging.2017.04.006.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.neurobiolaging.2017.04.006

AUTORES / AUTHORS: - Cole JH; et al.

INSTITUCIÓN / INSTITUTION: - Computational, Cognitive & Clinical Neuroimaging Laboratory (C3NL), Division of Brain Sciences, Imperial College London, London, UK.   james.cole@imperial.ac.uk

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer’s disease-factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [11C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants’ was +2.49 years, significantly greater than controls (p < 0.001). The variability in brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment.

TÍTULO / TITLE:    - The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome.

REVISTA / JOURNAL:    - Neuropathol Appl Neurobiol. 2017 Apr 28. doi: 10.1111/nan.12406.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/nan.12406

AUTORES / AUTHORS: - Milenkovic I; et al

INSTITUCIÓN / INSTITUTION: - Department of Neurology, Medical University of Vienna, Vienna, Austria.;Institute of Neurology, Neurodegeneration Research Group, Medical University of Vienna, Vienna, Austria.  

RESUMEN / SUMMARY: - AIMS: Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion. METHODS: Using morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life. RESULTS: We observed in DS a critical loss of physiological phosphorylation of tau. Rhombencephalic structures showed prominent differences between controls and DS using antibodies AT8 (Ser-202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau did not differ between groups, as confirmed by immunostaining for the HT-7 antibody (epitope between 159 and 163 of the human tau) as well. DISCUSSION: Our observations suggest functional tau disturbance in DS brains during development, rather than axonal loss. This supports the role of tau as a further important player in the pathophysiology of cognitive impairment in DS and related AD.

TÍTULO / TITLE:    - A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.

REVISTA / JOURNAL:    - J Alzheimers Dis. 2017;58(2):401-411. doi: 10.3233/JAD-160965.

Enlace a la Editora de la Revista http://dx.doi.org/10.3233/JAD-160965

AUTORES / AUTHORS: - Rafii MS; et al.

INSTITUCIÓN / INSTITUTION: - Alzheimer’s Therapeutic Research Institute (ATRI) at University of Southern California, San Diego, CA, USA.; Department of Neurosciences, University of California, San Diego, CA, USA.  

RESUMEN / SUMMARY: - BACKGROUND: ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer’s disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. OBJECTIVE: To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. RESULTS: There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. CONCLUSION: Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.

TÍTULO / TITLE:    - Hippocampal overexpression of Down syndrome cell adhesion molecule in amyloid precursor protein transgenic mice.

REVISTA / JOURNAL:    - Braz J Med Biol Res. 2017 May 15;50(6):e6049. doi: 10.1590/1414-431X20176049.

AUTORES / AUTHORS: - Jia YL; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, China.; The Central Hospital of Kaifeng, Kaifeng, Henan Province, China.  

RESUMEN / SUMMARY: - Down syndrome cell adhesion molecule (DSCAM) is located within the Down syndrome critical region of chromosome 21. DSCAM is a broadly expressed neurodevelopmental protein involved in synaptogenesis, neurite outgrowth, and axon guidance. We previously demonstrated DSCAM overexpression in the cortex of amyloid precursor protein (APP) transgenic mice, suggesting possible regulatory interactions between APP and DSCAM. APP mice exhibit deficits in hippocampus-dependent learning and memory. In this preliminary study, we examined age-related changes in DSCAM expression within the hippocampus in 16 APP transgenic mice (1, 3, 6 and 12 months old). Hippocampus-dependent spatial memory was assessed in APP mice and age-matched wild type littermates (WTs) using the Morris water maze (MWM). The cellular distribution of hippocampal DSCAM and total expression at both mRNA and protein levels were measured by immunohistochemistry, qRT-PCR, and western blotting, respectively. APP mice exhibited spatial memory deficits in the MWM. Intense DSCAM immunoreactivity was observed in the dentate gyrus granule cell layer and hippocampal stratum pyramidale. Total hippocampal DSCAM mRNA and protein expression levels were substantially higher in APP mice than WTs at 1 and 3 months of age. Expression decreased with age in both groups but remained higher in APP mice. DSCAM is overexpressed in the hippocampus over the first 12 months of life in APP mice, but especially during maturation to adulthood. In conclusion, these results suggest an association between DSCAM and APP mice, which is characterized by neuropathology and behavioral deficits. These results provide some clues for future studies on the role of DSCAM overexpression in the precocious cognitive decline observed in APP transgenic mice.

TÍTULO / TITLE:    - Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal-dominant Alzheimer’s disease.

REVISTA / JOURNAL:    - Alzheimers Dement. 2017 Apr 29. pii: S1552-5260(17)30146-2. doi: 10.1016/j.jalz.2017.03.007.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jalz.2017.03.007

AUTORES / AUTHORS: - Carmona-Iragui M; ... Fortea J;

INSTITUCIÓN / INSTITUTION: - Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autonoma de Barcelona, Barcelona, España; Barcelona Down Medical Center, Fundacio Catalana de Sindrome de Down,   jfortea@santpau.cat

RESUMEN / SUMMARY: - We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer’s disease (AD) (early-onset AD [EOAD]). METHODS: Neuroimaging features of CAA, apolipoprotein (APOE), and cerebrospinal fluid amyloid beta (Abeta) 40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68). RESULTS: CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. APOE epsilon4 genotype was borderline significantly associated with CAA in sporadic EOAD (P = .06) but not with DS or ADAD. There were no differences in Abeta040 levels between groups or between subjects with and without CAA. DISCUSSION: CAA is more frequently found in genetically determined AD than in sporadic EOAD. Cerebrospinal fluid Abeta40 levels are not a useful biomarker for CAA in AD.

TÍTULO / TITLE:    - Cerebrospinal fluid biomarkers for Alzheimer’s disease in Down syndrome.

REVISTA / JOURNAL:    - Alzheimers Dement (Amst). 2017 Mar 20;8:1-10. doi: 10.1016/j.dadm.2017.02.006. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.dadm.2017.02.006

AUTORES / AUTHORS: - Dekker AD; et al.c

INSTITUCIÓN / INSTITUTION: - Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands, Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Antwer  

RESUMEN / SUMMARY: - Down syndrome (DS), present in nearly six million people, is associated with an extremely high risk to develop Alzheimer’s disease (AD). Amyloid-beta and tau pathology are omnipresent from age 40 years onward, but clinical symptoms do not appear in all DS individuals. Dementia diagnostics is complex in this population, illustrating the great need for predictive biomarkers. Although blood biomarkers have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid-beta42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the general population and are increasingly used in clinical practice. Surprisingly, CSF biomarkers have been barely evaluated in DS. Breaking the taboo on CSF analyses would finally allow for the elucidation of its utility in (differential) diagnoses and staging of disease severity. A sensitive and specific biomarker profile for AD in DS would be of paramount importance to daily care, adaptive caregiving, and specific therapeutic interventions.

TÍTULO / TITLE:    - Pharmacokinetic Properties of Memantine Following a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down’s Syndrome.

REVISTA / JOURNAL:    - Basic Clin Pharmacol Toxicol. 2017 May 30. doi: 10.1111/bcpt.12816.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/bcpt.12816

AUTORES / AUTHORS: - Victorino DB; et al.

INSTITUCIÓN / INSTITUTION: - Division of Neurology and Epilepsy, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.  

RESUMEN / SUMMARY: - Memantine is a drug approved for the treatment of moderate-to-severe Alzheimer’s disease (AD), and there is ongoing research on the potential expansion of its clinical applicability. Published data on the pharmacokinetics of memantine in the mouse is still incomplete, particularly for chronic administration regimens and mouse models of specific genetic disorders. Down’s syndrome (DS) is a genetic disorder known to affect multiple organs and systems, with the potential to alter significantly drug pharmacokinetics. Here, we describe a simple, efficient and sensitive GC/MS-based procedure for the determination of memantine concentrations in murine blood and tissue samples. We analysed pharmacokinetic properties of memantine, particularly its distribution in blood, brain and liver in the Ts65Dn mouse model of DS and euploid F1 hybrid mice after single intraperitoneal administrations of increasing doses of this drug. We also determined steady-state memantine concentrations in plasma, brain and liver following chronic oral administration of this drug in adult male Ts65Dn mice, euploid littermate controls and nursing or pregnant Ts65Dn mice. Our results revalidated the acute dose of memantine used in previously published work, determined the appropriate amount of memantine to be mixed into mouse chow to achieve steady and pharmacologically relevant plasma and tissue levels of this drug, and demonstrated that memantine can be transferred from mother to offspring via maternal milk and placenta. Most of these findings are potentially applicable not only to the study of DS but also to other neurodevelopmental and neurodegenerative disorders.

TÍTULO / TITLE:    - Down syndrome, increased risk of dementia and lipid disturbances.

REVISTA / JOURNAL:    - Dev Period Med. 2017;21(1):69-73.

AUTORES / AUTHORS: - Klosowska A; et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Hematology and Oncology, Department of General Nursery Medical University of Gdansk, Poland.  

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common chromosomal aberration and genetically determined cause of intellectual disability. DS patients often present with some congenital defects and chronic diseases, including early onset dementia, which affects 70% of DS patients over 55 years of age and has a clinical presentation similar to Alzheimer disease (AD). The symptoms of DS originate from excessive genetic material within the “critical region” of the 21st chromosome. The “critical region” encompasses genes potentially associated with increase risk of dementia, e.g. the APP gene (amyloid beta precursor protein) which leads to excessive amyloid beta production. Post-mortem studies of DS patients’ brains revealed diffuse deposition of the insoluble form of amyloid beta (Abeta), which is a characteristic feature of AD. Moreover, those changes were commonly observed in subjects > 31 years old. The pathomechanisms of AD have not been fully elucidated and scientists are still searching for new risk factors that may contribute to the development of this common illness. Recent research proved that lipid disturbance, especially disorders in the metabolism of HDL (high density lipoprotein) may play a crucial role in this pathogenic process. There are many studies examining lipid and lipoprotein concentration in the DS population, but up to now there are insufficient studies comparing these parameters with memory impairment, which may be a useful model for better understanding of the dementia pathomechanism.

TÍTULO / TITLE:    - Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice.

REVISTA / JOURNAL:    - Sci Rep. 2017 Apr 4;7(1):619. doi: 10.1038/s41598-017-00682-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-017-00682-y

AUTORES / AUTHORS: - Yin X; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, 10314, USA.;Key Laboratory of Neuroregeneration of Jiangsu and Ministry of  

RESUMEN / SUMMARY: - ch is equally expressed in adult human brain. Imbalanced expression in 3R-tau and 4R-tau has been found in several sporadic and inherited tauopathies, suggesting that dysregulation of tau exon 10 is sufficient to cause neurodegenerative diseases. We previously reported that Dyrk1A, which is overexpressed in Down syndrome brains, regulates alternative splicing of exogenous tau exon 10. In the present study, we investigated the regulation of endogenous tau exon 10 splicing by Dyrk1A. We found that inhibition of Dyrk1A enhanced tau exon 10 inclusion, leading to an increase in 4R-tau/3R-tau ratio in differentiated-human neuronal progenitors and in the neonatal rat brains. Accompanied with overexpression of Dyrk1A, 3R-tau was increased and 4R-tau was decreased in the neonatal brains of Ts65Dn mice, a model of Down syndrome. Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. Thus, Dyrk1A might be an ideal therapeutic target for Alzheimer’s disease, especially for Down syndrome and EGCG which inhibits Dyrk1A may have potential effect on the treatment or prevention of this disease.

CARDIOLOGY - CARDIOLOGÍA

TÍTULO / TITLE:    - Attrition in patients with single ventricle and trisomy 21: outcomes after a total cavopulmonary connection.

REVISTA / JOURNAL:    - Interact Cardiovasc Thorac Surg. 2017 May 1;24(5):747-754. doi: 10.1093/icvts/ivw413.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/icvts/ivw413

AUTORES / AUTHORS: - Polimenakos AC;et al.

INSTITUCIÓN / INSTITUTION: - Division of Pediatric Cardiovascular Surgery, Advocate Children’s Hospital, Oak Lawn, IL, USA.; Children’s Hospital of Georgia Heart Center, Medical College of Georgia, Augusta, GA, USA.  

RESUMEN / SUMMARY: - Data are limited regarding the management of children with trisomy 21 (T21) syndrome and a functional single ventricle (FSV). We evaluated patients with T21 and a FSV who had a total cavopulmonary connection (TCPC). METHODS: From September 1999 to August 2012, 139 patients with a FSV underwent a TCPC. Sixty-five had unbalanced atrioventricular septal defect. Thirteen had T21. Three (of 13) had heterotaxy syndrome. The mean age at the Fontan operation was 27.6 +/- 12.1 months. RESULTS: The initial procedure was pulmonary artery banding in 9 patients, systemic-to-pulmonary shunt in 2 and Damus-Kaye-Stansel/Norwood procedure in 2. Median follow-up was 69 months (interquartile range 25-75, 21-99). There was 1 death after a Damus-Kaye-Stansel/Norwood procedure and one interstage death after a bidirectional Glenn procedure. Nine (of 11) survivors underwent a Fontan operation. A fenestrated Fontan procedure was the predominate operation in 78%. One patient was deemed unsuitable for a Fontan operation. There was 1 takedown and 1 late death after the Fontan operation. Heterotaxy syndrome did not affect outcome ( P > 0.05). There was no statistical difference in the pre-Fontan McGoon ratio, hospital length of stay, duration of pleural drainage and Fontan-related adverse events between patients with a dominant right ventricle and those with a left ( P > 0.05). CONCLUSIONS: A TCPC in patients with T21 and an FSV is associated with reproducible, satisfactory outcomes. An assisted-Glenn procedure with pulsatile pulmonary blood flow and a fenestrated Fontan may be associated with attenuated perioperative morbidity and late attrition.

DENTAL - DENTAL

TÍTULO / TITLE:    - Congenital Absence of Salivary Glands in Fetuses with Trisomy 21.

REVISTA / JOURNAL:    - Isr Med Assoc J. 2017 Jan;19(1):12-14.

Enlace a la Editora de la Revista Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Israel.;Galilee Faculty of Medicine, Bar Ilan University, Safed, Israel.

AUTORES / AUTHORS: - Odeh M; Bronshtein M;Bornstein J;

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Galilee Faculty of Medicine,University of Haifa, Bar Ilan University, Safed, Galilee Medical Center, Nahariya, Israel  

RESUMEN / SUMMARY: - BACKGROUND: The congenital absence of salivary glands has been reported in children but never in fetuses with trisomy 21. OBJECTIVES: To determine whether the congenital absence of salivary glands can be detected prenatally between 13 and 16 weeks of gestation in normal and trisomy 21 fetuses using transvaginal ultrasound. METHODS: We performed a retrospective analysis of recordings of normal and trisomy 21 fetuses. Inclusion criteria were a single viable fetus and good visualization of the anatomic area of the salivary glands on both sides of the fetal face. All videos were reviewed by one examiner who reported the presence or absence of one or more salivary glands and was blinded to the fetal karyotype. RESULTS: Of the 45 videos reviewed, 4 were excluded from the study: namely, a non-viable fetus, twin pregnancy, and in 2 there was unsatisfactory visualization of the anatomic area of the salivary glands. Of the remaining 41 fetuses, 24 had trisomy 21 and 17 were normal. In the trisomy 21 fetuses, 8 (33.3%) had congenital absence of one or more salivary glands compared to 1 of 17 normal fetuses (5.9%) (P < 0.05). CONCLUSIONS: Congenital absence of the salivary glands has a high specificity but low sensitivity for detecting trisomy 21 fetuses.

TÍTULO / TITLE:    - Effectiveness of audiovisual distraction with computerized delivery of anesthesia during the placement of stainless steel crowns in children with Down syndrome.

REVISTA / JOURNAL:    - Eur J Dent. 2017 Jan-Mar;11(1):1-5. doi: 10.4103/ejd.ejd_288_16.

Enlace a la Editora de la Revista http://dx.doi.org/10.4103/ejd.ejd_288_16

AUTORES / AUTHORS: - Fakhruddin KS; et al

INSTITUCIÓN / INSTITUTION: - Department of Preventive and Restorative Dentistry, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Department of Endodontics, Faculty of Dentistry, Hacettepe University, Ankara, Turkiye.  

RESUMEN / SUMMARY: - Assessing effectiveness of audiovisual (AV) distraction with/without video eyewear and computerized delivery system-intrasulcular (CDS-IS) for local anesthesia during placement of stainless steel crowns for the management of pathological tooth grinding in children with Down syndrome. MATERIALS AND METHODS: This clinical study includes 22 children (13 boys and 9 girls), with mean age being 7.1 years. The study involved three sessions 1-week apart. During Session I, dental prophylaxis to the upper jaw was done while watching a movie projected on the ceiling without video eyewear whereas prophylaxis for the lower jaw and impressions of both jaws were taken while watching another movie using eyewear projection. After 1 week, during Session II/III, children had their upper and lower second primary molars which were prepared and steel crowns inserted, respectively, while watching movies which were projected using video eyewear under the effect of CDS-IS local anesthesia. Changes in pulse oximeter and heart rate were recorded every 5 min. Independent sample t-test was used to assess significance of changes during each visit. RESULTS: A statistically significant difference (P < 0.03) was observed in mean pulse rate between dental prophylaxis without video eyewear and during dental prophylaxis and dental impression taken while children were distracted using AV distracter with video eyewear. We observed an increase in mean pulse rate during tooth preparation use dental drills, but this does not lead to disruptive behavior as children were being distracted by AV distracter with video eyewear. CONCLUSION: Routine psychological (Tell-Show-Do) intervention along with visual distraction using video eyewear and use of CDS-IS system for anesthetic delivery is recommended as an effective behavior management technique for children with Down syndrome during invasive dental treatment.

EAR/NASAL - OTORRINOLARINGOLOGÍA

TÍTULO / TITLE:    - Obstructive sleep apnea in Down syndrome: Benefits of surgery and noninvasive respiratory support.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 May 24. doi: 10.1002/ajmg.a.38283.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38283

AUTORES / AUTHORS: - Dudoignon B; et al

INSTITUCIÓN / INSTITUTION: - AP-HP, Hopital Necker-Enfants Malades, Pediatric Noninvasive Ventilation and Sleep Unit, Paris, France.  

RESUMEN / SUMMARY: - Children with Down syndrome are at increased risk of obstructive sleep apnea (OSA). The aim of the study was to describe the management of OSA in a large cohort of children with Down syndrome. A retrospective analysis of sleep studies and consequent management was performed for all consecutive Down syndrome patients evaluated between September 2013 and April 2016. The data of 57 patients were analyzed: 51/53 had an interpretable overnight polygraphy and 4 the recording of nocturnal gas exchange. Mean age at baseline sleep study was 6.2 +/- 5.9 years. Eighteen patients (32%) had prior upper airway surgery. Mean apnea-hypopnea index (AHI) was 14 +/- 16 events/hr with 41 of the 51 (80%) patients having OSA with an AHI> 1 event/hr and 20 patients (39%) having an AHI >/=10 events/hr. Consequently, eight patients (14%) had upper airway surgery. OSA improved in all patients except two who needed noninvasive respiratory support. Nineteen (33%) patients required noninvasive respiratory support. Mean age at noninvasive respiratory support initiation was 7 +/- 7 years. On 11 patients with objective adherence data available, mean compliance at 2 +/- 1 years of treatment was excellent with an average use per night of 8 hr46 +/- 3 hr59 and 9 patients using the noninvasive respiratory support >4 hr/night. Noninvasive respiratory support was associated with an improvement of nocturnal gas exchange. The prevalence of OSA is high in Down syndrome. Upper airway surgery is not always able to correct OSA. Noninvasive respiratory support represents then an effective treatment for OSA and good compliance may be achieved in a majority of patients.

TÍTULO / TITLE:    - The Efficacy of Adenotonsillectomy for Obstructive Sleep Apnea in Children with Down Syndrome: A Systematic Review.

REVISTA / JOURNAL:    - Otolaryngol Head Neck Surg. 2017 May 1:194599817703921. doi: 10.1177/0194599817703921.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0194599817703921

AUTORES / AUTHORS: - Nation J; Brigger M

INSTITUCIÓN / INSTITUTION: - 1 Otolaryngology/Head and Neck Surgery, Rady Children’s Hospital San Diego/University of California, San Diego, San Diego, California, USA.  

RESUMEN / SUMMARY: - Objective Determine the efficacy of adenotonsillectomy in children with Down syndrome. Data Sources Databases included PubMed, EMBASE, CINAHL, and Google Scholar. The search was inclusive of all references available through January 5, 2017. Review Methods A systematic review of the medical literature addressing adenotonsillectomy in treating obstructive sleep apnea in children with Down syndrome was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were pooled using a random-effects model where possible. The quality of studies was graded using the Methodological Index for Nonrandomized Studies criteria. Results Of the 957 articles screened, 5 met inclusion for the qualitative analysis and 3 met criteria for the quantitative analysis. The findings of the qualitative analysis were that adenotonsillectomy has a positive effect on children with Down syndrome but in many cases is noncurative, up to 75% need postoperative breathing support, there is a high rate of immediate postoperative airway needs, and there is no change in sleep efficiency or architecture. The articles consistently reported moderate success in improving polysomnographic parameters, and limited pooling of the data demonstrated a mean decrease of the apnea-hypopnea index by 51% (95% confidence interval [CI], 46%-55%). Conclusion A 51% reduction in the preoperative apnea-hypopnea index can be expected with the intervention of adenotonsillectomy alone in children with Down syndrome. This information is useful for counseling and managing patient and family expectations. It also serves as a reminder to clinicians to obtain a postoperative sleep study, as many of these patients will need nighttime airway support or secondary sleep surgery.

TÍTULO / TITLE:    - The effect of adenotonsillectomy on obstructive sleep apnea in children with Down syndrome.

REVISTA / JOURNAL:    - Acta Otolaryngol. 2017 Apr 11:1-8. doi: 10.1080/00016489.2017.1312016.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/00016489.2017.1312016

AUTORES / AUTHORS: - Abdel-Aziz M; et al

INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology, Faculty of Medicine , Cairo University , Cairo , Egypt.  

RESUMEN / SUMMARY: - Children with Down syndrome (DS) are liable to develop obstructive sleep apnea (OSA) due to many anatomical airway abnormalities. The tonsils and adenoid occupy part of the airway space, and their removal may be helpful in relieving airway obstruction. The aim of this study was to assess the effectiveness of adenotonsillectomy in the treatment of OSA in those children. METHODS: Fifty DS children with difficult breathing were recruited, and they were subjected to polysomnographic examination (PSG). Patients with apnea-hypopnea index (AHI) > 1 were considered to have OSA. Adenotonsillectomy was performed for patients who had OSA and adenotonsillar hypertrophy, and after 3 months PSG was done for them with recording of the same preoperative parameters. RESULTS: Forty-three children demonstrated OSA on PSG, and they were included in the study. The preoperative mean AHI was 9.18 (+/- 6.17) that improved postoperatively to 2.72 (+/- 3.80) with its normalization in 72% of patients. Also, significant improvement of arousal index, minimum oxygen saturation, desaturation index, and peak end-tidal CO2 was achieved postoperatively. CONCLUSION: Adenotonsillectomy is an effective method for the treatment of OSA in children with DS. However, the condition may persist in some children who usually have airway narrowing at multiple levels.

TÍTULO / TITLE:    - Wideband acoustic immittance in children with Down syndrome: prediction of middle-ear dysfunction, conductive hearing loss and patent PE tubes.

REVISTA / JOURNAL:    - Int J Audiol. 2017 Apr 22:1-13. doi: 10.1080/14992027.2017.1314557.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/14992027.2017.1314557

AUTORES / AUTHORS: - Hunter LL; ... Shott SR

INSTITUCIÓN / INSTITUTION: - a Divisions of Otolaryngology and. Audiology , Cincinnati Children’s Hospital Medical Center , Cincinnati , OH , USA.  

RESUMEN / SUMMARY: - The purpose of this study was to evaluate pressurised wideband acoustic immittance (WAI) tests in children with Down syndrome (DS) and in typically developing children (TD) for prediction of conductive hearing loss (CHL) and patency of pressure equalising tubes (PETs). DESIGN: Audiologic diagnosis was determined by audiometry in combination with distortion-product otoacoustic emissions, 0.226 kHz tympanometry and otoscopy. WAI results were compared for ears within diagnostic categories (Normal, CHL and PET) and between groups (TD and DS). STUDY SAMPLE: Children with DS (n = 40; mean age 6.4 years), and TD children (n = 48; mean age 5.1 years) were included. RESULTS: Wideband absorbance was significantly lower at 1-4 kHz in ears with CHL compared to NH for both TD and DS groups. In ears with patent PETs, wideband absorbance and group delay (GD) were larger than in ears without PETs between 0.25 and 1.5 kHz. Wideband absorbance tests were performed similarly for prediction of CHL and patent PETs in TD and DS groups. CONCLUSIONS: Wideband absorbance and GD revealed specific patterns in both TD children and those with DS that can assist in detection of the presence of significant CHL, assess the patency of PETs, and provide frequency-specific information in the audiometric range.

ENDOCRINOLOGY/NUTRITION - ENDOCRINOLOGÍA/NUTRICIÓN

TÍTULO / TITLE:    - Incorporating thyroid markers in Down syndrome screening protocols.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 May;37(5):510-514. doi: 10.1002/pd.5047. Epub 2017 Apr 24.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5047

AUTORES / AUTHORS: - Dhaifalah I et al.

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, Columbia University Medical Centre, New York, NY, USA.  

RESUMEN / SUMMARY: - OBJECTIVE: The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. METHODS: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. RESULTS: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. CONCLUSIONS: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost.

GENETICS - GENÉTICA

TÍTULO / TITLE:    - Generation of Integration-Free Induced Pluripotent Stem Cells from Urine-Derived Cells Isolated from Individuals with Down Syndrome.

REVISTA / JOURNAL:    - Stem Cells Translational Medicine 2017;6:1465-1476. http://stemcells.alphamedpress.org/

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/sctm.16-0128

AUTORES / AUTHORS: - M Lee Y; et al

INSTITUCIÓN / INSTITUTION: - Division of Pediatric Neurology, Department of Pediatrics.  

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetic disorder caused by trisomy 21 (T21). Over the past two decades, the use of mouse models has led to significant advances in the understanding of mechanisms underlying various phenotypic features and comorbidities secondary to T21 and even informed the design of clinical trials aimed at enhancing the cognitive abilities of persons with DS. In spite of its success, this approach has been plagued by all the typical limitations of rodent modeling of human disorders and diseases. Recently, several laboratories have succeeded in producing T21 human induced pluripotent stem cells (T21-iPSCs) from individuals with DS, which is emerging as a promising complementary tool for the study of DS. Here, we describe the method by which we generated 10 T21-iPSC lines from epithelial cells in urine samples, presumably from kidney epithelial origin, using nonintegrating episomal vectors. We also show that these iPSCs maintain chromosomal stability for well over 20 passages and are more sensitive to proteotoxic stress than euploid iPSCs. Furthermore, these iPSC lines can be differentiated into glutamatergic neurons and cardiomyocytes. By culturing urine-derived cells and maximizing the efficiency of episomal vector transfection, we have been able to generate iPSCs noninvasively and effectively from participants with DS in an ongoing clinical trial, and thus address most shortcomings of previously generated T21-iPSC lines. These techniques should extend the application of iPSCs in modeling DS and other neurodevelopmental and neurodegenerative disorders, and may lead to future human cell-based platforms for high-throughput drug screening.

TÍTULO / TITLE:    - A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation.

REVISTA / JOURNAL:    - Sci Rep. 2017 Apr 10;7(1):764. doi: 10.1038/s41598-017-00714-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-017-00714-7

AUTORES / AUTHORS: - Omori S; et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.;  

RESUMEN / SUMMARY: - Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and the three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence of supernumerary chromosome 21 in Down syndrome may perturb the nuclear architecture at different levels, which is normally optimised to maintain the physiological balance of gene expression. However, it has not been clearly elucidated whether and how aberrant configuration of chromosomes affects gene activities. To investigate the effects of trisomy 21 on nuclear organisation and gene expression, we performed three-dimensional fluorescent imaging analysis of chromosome-edited human induced pluripotent stem cells (iPSCs), which enabled identification of the parental origin of the three copies of chromosome 21. We found that two copies of maternal chromosomes resulting from meiotic nondisjunction had a higher tendency to form an adjacent pair and were located relatively distant from the nuclear membrane, suggesting the conserved interaction between these homologous chromosomes. Transcriptional profiling of parental-origin-specific corrected disomy 21 iPSC lines indicated upregulated expression of the maternal alleles for a group of genes, which was accompanied by a fluctuating expression pattern. These results suggest the unique effects of a pair of maternal chromosomes in trisomy 21, which may contribute to the pathological phenotype.

GROWTH/DEVELOPMENT - CRECIMIENTO/DESARROLLO

TÍTULO / TITLE:    - Comparison of bioelectrical impedance and DXA for measuring body composition among adults with Down syndrome.

REVISTA / JOURNAL:    - Disabil Health J. 2017 Mar 22. pii: S1936-6574(17)30051-1. doi: 10.1016/j.dhjo.2017.03.009.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.dhjo.2017.03.009

AUTORES / AUTHORS: - Esco MR; et al

INSTITUCIÓN / INSTITUTION: - Department of Kinesiology, University of Alabama, USA.   mresco@bamaed.ua.edu

RESUMEN / SUMMARY: - BACKGROUND: Individuals with Down syndrome (DS) have been shown to display high levels of adiposity and a unique body shape. Laboratory methods used to evaluate body composition might be too cumbersome for this special population. Therefore, field methods are desired due to their non-invasive nature. OBJECTIVE: to determine the agreement between dual energy x-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) for measuring body fat percentage BF% and fat-free mass (FFM) among adults with DS. METHODS: Twenty-one adults (male: n = 10; female: n = 11) with DS participated in this study. BF% and FFM were determined by DXA and BIA. RESULTS: There was a significant mean difference between DXA and BIA for BF% (41.33 +/- 8.98% and 34.23 +/- 9.22%, respectively) and FFM (41.80 +/- 8.74 kg and 46.95 +/- 9.92 kg, respectively). The correlation between the two devices for BF% and FFM were significant (r = 0.89 and r = 0.94, respectively, p < 0.001 for both). The standard error of estimate and total error values were 4.38% and 8.27%, respectively, for BF% and 3.04 kg and 6.13 kg, respectively, for FFM. The 95% limits of agreement ranged from -15.64% below to 1.46% above the constant error (CE) of -7.09% for BF% and from -1.52 kg below to 11.83 kg above the CE of 5.15 kg for FFM. CONCLUSIONS: The significant mean differences and large amount of individual error suggest that BIA may not be an appropriate surrogate body composition measure compared to DXA in adults with DS.

HEMATOLOGY/ONCOLOGY - HEMATOLOGÍA/ONCOLOGÍA

TÍTULO / TITLE:    - Therapy reduction in patients with Down Syndrome Myeloid Leukemia: The international ML-DS 2006 trial.

REVISTA / JOURNAL:    - Blood. 2017 Apr 11. pii: blood-2017-01-765057. doi: 10.1182/blood-2017-01-765057.

Enlace a la Editora de la Revista http://dx.doi.org/10.1182/blood-2017-01-765057

AUTORES / AUTHORS: - Uffmann M; Rasche M; Zimmermann M; von Neuhoff C; Creutzig U; Dworzak M; Scheffers L; Hasle H; Zwaan CM; Reinhardt D; Klusmann JH;

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany.   klusmann.jan-henning@mh-hannover.de

RESUMEN / SUMMARY: - Children with Down syndrome and myeloid leukemia (ML-DS) have a superior outcome compared to non-DS patients, but suffer from higher constitutional susceptibility to cytotoxic drugs. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multi-center, open-label, non-randomized ML-DS 2006 trial, by the NOPHO, DCOG and AML-BFM study groups. In comparison to the historical control arm (reduced intensity protocol for ML-DS patients from the AML-BFM 98 trial) treatment intensity was reduced by lowering the cumulative dose of etoposide (950 mg/m2 to 450 mg/m2) and intrathecal CNS-prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (5yr-OS; 89+/-;3% vs. 90+/-;4%, Plog-rank=0.64), event-free survival (5yr-EFS; 87+/-;3% vs. 89+/-;4%, Plog-rank=0.71) and cumulative incidence of relapse/non-response (CIR; 6+/-;3% vs. 6+/-;2%, PGray=0.03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5yr-EFS 58+/-;16% vs. 88+/-;3% Plog rank=0.0008) and gain of chromosome 8 (CIR 16+/-;7% vs 3+/-;2%, PGray=0.02; 5yr-EFS 73+/-;8% vs 91+/-;4%, Plog rank=0.018) were identified as independent prognostic factors predicting a worse EFS. Five out of seven relapsed patients (71%) with cytogenetic data had trisomy 8. Thus, our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair the excellent outcome. The trial was registered at EudraCT as -2007-006219-2.

TÍTULO / TITLE:    - Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children’s Oncology Group AAML0431 trial

REVISTA / JOURNAL:    - Blood. 2017 Apr 7. pii: blood-2017-01-764324. doi: 10.1182/blood-2017-01-764324.

Enlace a la Editora de la Revista http://dx.doi.org/10.1182/blood-2017-01-764324

AUTORES / AUTHORS: - Taub JW; Berman JN; Hitzler JK; Sorrell AD; Lacayo NJ; Mast K; Head D; Raimondi S; Hirsch B; Ge Y; Gerbing RB; Wang YC; et al.

INSTITUCIÓN / INSTITUTION: - Division of Hematology/Oncology, Children’s Hospital of Michigan, Wayne State University, Detroit, MI, United States   jtaub@med.wayne.edu

RESUMEN / SUMMARY: - Patients with myeloid leukemia of Down syndrome (ML-DS) have a favorable event-free survival (EFS), but experience significant treatment-related morbidity and mortality. ML-DS blast cells ex vivo have increased sensitivity to cytarabine (araC) and daunorubicin, suggesting that optimizing drug dosing may improve outcomes while reducing toxicity. The Children’s Oncology Group (COG) AAML0431 trial consisted of 4 cycles of Induction and 2 cycles of Intensification therapy based on the treatment schema of the previous COG A2971 trial with several modifications. High-dose araC (HD-araC) was used in the second Induction cycle instead of the Intensification cycle and one of four daunorubicin containing induction cycles was eliminated. For 204 eligible patients, 5-year EFS was 89.9% and overall survival (OS) was 93.0%. The 5-year OS for 17 patients with refractory/relapsed leukemia was 34.3%. We determined the clinical significance of minimal residual disease (MRD) levels as measured by flow cytometry on day 28 of Induction I. MRD measurements, available for 146 of the 204 patients, were highly predictive of treatment outcome; 5-year disease-free survival for MRD-negative patients (n=125) was 92.7% versus 76.2% for MRD-positive patients (n=21) (log-rank P =0.011). Our results indicated that earlier use of HD-araC led to better EFS and OS in AAML0431 than in past COG studies. A 25% reduction in the cumulative daunorubicin dose did not impact outcome. MRD, identified as a new prognostic factor for ML-DS patients, can be used for risk stratification in future clinical trials. The trial was registered at https://clinicaltrials.gov/ as NCT00369317.

TÍTULO / TITLE:    - Suppressors and activators of JAK-STAT signaling at diagnosis and relapse of acute lymphoblastic leukemia in Down syndrome.

REVISTA / JOURNAL:    - Proc Natl Acad Sci U S A. 2017 May 16;114(20):E4030-E4039. doi: 10.1073/pnas.1702489114. Epub 2017 M

Enlace a la Editora de la Revista http://dx.doi.org/10.1073/pnas.1702489114

AUTORES / AUTHORS: - Schwartzman O; ... Chen Z et al.

INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, China;   zchen@stn.sh.cn Arndt.Borkhardt@med.uni-duesseldorf.de sizraeli@sheba.health.gov.il

RESUMEN / SUMMARY: - Children with Down syndrome (DS) are prone to development of high-risk B-cell precursor ALL (DS-ALL), which differs genetically from most sporadic pediatric ALLs. Increased expression of cytokine receptor-like factor 2 (CRLF2), the receptor to thymic stromal lymphopoietin (TSLP), characterizes about half of DS-ALLs and also a subgroup of sporadic “Philadelphia-like” ALLs. To understand the pathogenesis of relapsed DS-ALL, we performed integrative genomic analysis of 25 matched diagnosis-remission and -relapse DS-ALLs. We found that the CRLF2 rearrangements are early events during DS-ALL evolution and generally stable between diagnoses and relapse. Secondary activating signaling events in the JAK-STAT/RAS pathway were ubiquitous but highly redundant between diagnosis and relapse, suggesting that signaling is essential but that no specific mutations are “relapse driving.” We further found that activated JAK2 may be naturally suppressed in 25% of CRLF2pos DS-ALLs by loss-of-function aberrations in USP9X, a deubiquitinase previously shown to stabilize the activated phosphorylated JAK2. Interrogation of large ALL genomic databases extended our findings up to 25% of CRLF2pos, Philadelphia-like ALLs. Pharmacological or genetic inhibition of USP9X, as well as treatment with low-dose ruxolitinib, enhanced the survival of pre-B ALL cells overexpressing mutated JAK2. Thus, somehow counterintuitive, we found that suppression of JAK-STAT “hypersignaling” may be beneficial to leukemic B-cell precursors. This finding and the reduction of JAK mutated clones at relapse suggest that the therapeutic effect of JAK specific inhibitors may be limited. Rather, combined signaling inhibitors or direct targeting of the TSLP receptor may be a useful therapeutic strategy for DS-ALL.

TÍTULO / TITLE:    - Treatment results in children with myeloid leukemia of Down syndrome in Saudi Arabia: A multicenter SAPHOS leukemia group study

REVISTA / JOURNAL:    - Leuk Res. 2017 Apr 12;58:48-54. doi: 10.1016/j.leukres.2017.04.004.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.leukres.2017.04.004

AUTORES / AUTHORS: - Jastaniah W; et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Faculty of Medicine, Umm AlQura University, Makkah, Saudi Arabia; Princess Noorah Oncology Center, King Saud Bin Abdulaziz University and King Abdulaziz Medical City, Jeddah, Saudi Arabia   jastaniahwa@ngha.med.sa

RESUMEN / SUMMARY: - Despite the high incidence of Down syndrome (DS) in Arab countires, the incidence and outcomes of myeloid leukemia of DS (ML-DS) have not been studied. We evaluated 206 pediatric acute myeloid leukemia (AML) patients diagnosed between 2005 and 2012 and identified 31 (15%) ML-DS. The incidence of ML-DS was 48 per 100,000 compared to 0.6 per 100,000 for AML in non-DS children. Thus, patients with DS had 80-fold increased risk of ML-DS compared to AML in non-DS children. The median age at diagnosis was 1.8 years, male/female ratio was 1.2, majority (84%) of patients had FAB-M7 subtype, and the cytogenetic abnormalities were normal karyotype (constitutional trisomy 21) in 48%, additional trisomy in 23%, and other aberrations in 29%. Complete remission, cumulative incidences of relapse (CIR), toxic-death, and 5-year event-free survival (EFS) rates were 96.8%, 19.4%, 13.1%, and 67.7+/-8.4%; respectively. In the present study, multivariate analysis revealed favorable outcome (5-year EFS 86.7+/-8.8%) for patients with normal karyotype. The incidence and clinical characteristics of ML-DS in Saudi patients were comparable to other reports. However, there is a need to optimize risk stratification and treatment intensity to reduce CIR and toxic death rates to further improve outcomes of patients with ML-DS.

TÍTULO / TITLE:    - Collagenoma in a Patient With Down Syndrome: A Case Report and Review of the Literature.

REVISTA / JOURNAL:    - Am J Dermatopathol. 2017 Mar 16. doi: 10.1097/DAD.0000000000000873.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/DAD.0000000000000873

AUTORES / AUTHORS: - Choi SY; Park S

INSTITUCIÓN / INSTITUTION: - Departments of *Radiology, and daggerPathology, Ewha Womans University School of Medicine, Seoul, Korea.  

RESUMEN / SUMMARY: - A 26-year-old woman with Down syndrome presented with a 4-cm-sized palpable mass in the sacrococcygeal region. Histologic evaluation of the specimen revealed densely packed collagen fibers in the dermis, which is consistent with a collagenoma. Masson trichrome staining showed dense fibrosis, and elastic Van Gieson staining revealed a significant decrease in elastic tissue. The clinicopathologic characteristics of this patient and 4 previously reported cases are discussed in detail.

TÍTULO / TITLE:    - Attrition in patients with single ventricle and trisomy 21: outcomes after a total cavopulmonary connection.

REVISTA / JOURNAL:    - Interact Cardiovasc Thorac Surg. 2017 May 1;24(5):747-754. doi: 10.1093/icvts/ivw413.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/icvts/ivw413

AUTORES / AUTHORS: - Polimenakos AC;et al.

INSTITUCIÓN / INSTITUTION: - Division of Pediatric Cardiovascular Surgery, Advocate Children’s Hospital, Oak Lawn, IL, USA.; Division of Pediatric Cardiothoracic Surgery, Children’s Hospital of Georgia Heart Center, Medical College of Georgia, Augusta, GA, USA  

RESUMEN / SUMMARY: - OBJECTIVES: Data are limited regarding the management of children with trisomy 21 (T21) syndrome and a functional single ventricle (FSV). We evaluated patients with T21 and a FSV who had a total cavopulmonary connection (TCPC). METHODS: From September 1999 to August 2012, 139 patients with a FSV underwent a TCPC. Sixty-five had unbalanced atrioventricular septal defect. Thirteen had T21. Three (of 13) had heterotaxy syndrome. The mean age at the Fontan operation was 27.6 +/- 12.1 months. RESULTS: The initial procedure was pulmonary artery banding in 9 patients, systemic-to-pulmonary shunt in 2 and Damus-Kaye-Stansel/Norwood procedure in 2. Median follow-up was 69 months (interquartile range 25-75, 21-99). There was 1 death after a Damus-Kaye-Stansel/Norwood procedure and one interstage death after a bidirectional Glenn procedure. Nine (of 11) survivors underwent a Fontan operation. A fenestrated Fontan procedure was the predominate operation in 78%. One patient was deemed unsuitable for a Fontan operation. There was 1 takedown and 1 late death after the Fontan operation. Heterotaxy syndrome did not affect outcome ( P > 0.05). There was no statistical difference in the pre-Fontan McGoon ratio, hospital length of stay, duration of pleural drainage and Fontan-related adverse events between patients with a dominant right ventricle and those with a left ( P > 0.05). CONCLUSIONS: A TCPC in patients with T21 and an FSV is associated with reproducible, satisfactory outcomes. An assisted-Glenn procedure with pulsatile pulmonary blood flow and a fenestrated Fontan may be associated with attenuated perioperative morbidity and late attrition.

INFECTIOUS DISEASES - INFECCIONES

TÍTULO / TITLE:    - Quantitative, phenotypical and functional characterization of cellular immunity in pediatric individuals with Down syndrome.

REVISTA / JOURNAL:    - J Infect Dis. 2017 Apr 4. doi: 10.1093/infdis/jix168.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/infdis/jix168

AUTORES / AUTHORS: - Schoch J; et al

INSTITUCIÓN / INSTITUTION: - Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.  

RESUMEN / SUMMARY: - Background: Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. While the role of B-cells and antibodies is well characterized, knowledge regarding T-cells is limited. Methods: Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T-cells were flow-cytometrically analyzed after polyclonal and pathogen-specific stimulation (varicella-zoster virus (VZV), cytomegalovirus (CMV)). Results were correlated with IgG-responses. Results: Apart from general alterations in the percentage of lymphocytes and regulatory T-cells, Th1-, and Th17-cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4 T-cell frequencies were significantly higher in Down syndrome while their inhibitory receptor-expression (PD-1 and CTLA-4) was similar to controls, and cytokine-expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV-IgG-positive individuals, a higher percentage of VZV-specific T-cell positive subjects was seen in Down syndrome. Conclusions: Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls, but may require higher effector T-cell frequencies to ensure pathogen control.

TÍTULO / TITLE:    - National cohort study showed that infants with Down’s syndrome faced a high risk of hospitalisation for the respiratory syncytial virus.

REVISTA / JOURNAL:    - Acta Paediatr. 2017 May 28. doi: 10.1111/apa.13937.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/apa.13937

AUTORES / AUTHORS: - Grut V; et al

INSTITUCIÓN / INSTITUTION: - Unit of Research, Education and Development, Ostersund Hospital, Ostersund, Sweden.  

RESUMEN / SUMMARY: - AIM: The respiratory syncytial virus (RSV) is a leading cause of hospitalisation in infants. We investigated this risk in children with Down’s syndrome under two years of age, adjusted for other known risk factors. METHODS: This national, retrospective 1:2 matched cohort study comprised all Swedish children born with Down’s from 2006-2011, who were each randomly matched to two controls without Down’s. Data on RSV hospitalisation and risk factors for RSV were obtained from national registers. The risk for RSV hospitalisation was assessed using multivariable Cox regression with pairwise stratification. RESULTS: The study comprised 814 children with Down’s and 1,628 controls. We found that 82 children with Down’s (10.1%) and 22 controls (1.4%) were hospitalised for RSV. The hazard ratio for children with Down’s was 4.00 (95% confidence interval 1.58-10.13) for up to one year of age and 6.60 (95% confidence interval 2.83-15.38) for up to two years of age, adjusted for other risk factors. During the second year of life, RSV hospitalisation continued for children with Down’s, while it was minimal for the controls. CONCLUSION: Children with Down’s faced a high risk of RSV hospitalisation, which continued beyond the first year of age.

TÍTULO / TITLE:    - Brain tuberculoma, an unusual cause of stroke in a child with trisomy 21: a case report.

REVISTA / JOURNAL:    - J Med Case Rep. 2017 Apr 18;11(1):114. doi: 10.1186/s13256-017-1258-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13256-017-1258-7

AUTORES / AUTHORS: - Kheir AEM; et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics and Child Health, Faculty of Medicine, University of Khartoum and Soba University Hospital, P.O. Box 102, Khartoum, Sudan.   moneimkheir62@hotmail.com

RESUMEN / SUMMARY: - BACKGROUND: Tuberculosis remains a public health problem in developing countries and is associated with lethal central nervous system complications. Intracranial tuberculomas occur in 13% of children with neurotuberculosis. Patients with trisomy 21 have an increased risk for stroke, which usually stems from cardiovascular defects. CASE PRESENTATION: We report a case of a 12-year-old Sudanese boy with trisomy 21 who was presented to our hospital with focal convulsions and right-sided weakness. The results of neuroimaging and histopathological examinations were consistent with cerebral tuberculoma. The patient had a good initial response to antituberculosis drugs and steroids. To the best of our knowledge, this is the first case report of multiple brain tuberculomas described in a child with trisomy 21. CONCLUSIONS: Patients with trisomy 21 have an increased risk for stroke. Our patient had an exceptional case of stroke caused by tuberculoma. The present case emphasizes the need to consider tuberculomas in the differential diagnosis of children with neurological symptoms living in areas of high tuberculosis incidence.

MOLECULAR BIOLOGY/BIOCHEMISTRY - BIOLOGÍA MOLECULAR/BIOQUÍMICA

TÍTULO / TITLE:    - The burden of trisomy 21 disrupts the proteostasis network in Down syndrome.

REVISTA / JOURNAL:    - PLoS One. 2017 Apr 21;12(4):e0176307. doi: 10.1371/journal.pone.0176307. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1371/journal.pone.0176307

AUTORES / AUTHORS: - Aivazidis S; et al

INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, United States of America.  

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21. Abnormalities in chromosome number have the potential to lead to disruption of the proteostasis network (PN) and accumulation of misfolded proteins. DS individuals suffer from several comorbidities, and we hypothesized that disruption of proteostasis could contribute to the observed pathology and decreased cell viability in DS. Our results confirm the presence of a disrupted PN in DS, as several of its elements, including the unfolded protein response, chaperone system, and proteasomal degradation exhibited significant alterations compared to euploid controls in both cell and mouse models. Additionally, when cell models were treated with compounds that promote disrupted proteostasis, we observed diminished levels of cell viability in DS compared to controls. Collectively our findings provide a cellular-level characterization of PN dysfunction in DS and an improved understanding of the potential pathogenic mechanisms contributing to disrupted cellular physiology in DS. Lastly, this study highlights the future potential of designing therapeutic strategies that mitigate protein quality control dysfunction.

TÍTULO / TITLE:    - Systematic review and meta-analysis shows a specific micronutrient profile in people with Down Syndrome: Lower blood calcium, selenium and zinc, higher red blood cell copper and zinc, and higher saliv

REVISTA / JOURNAL:    - PLoS One. 2017 Apr 19;12(4):e0175437. doi: 10.1371/journal.pone.0175437. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1371/journal.pone.0175437

AUTORES / AUTHORS: - Saghazadeh A; et al

INSTITUCIÓN / INSTITUTION: - Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran.;MetaCognition Interest Group (MCIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.  

RESUMEN / SUMMARY: - Different metabolic profiles as well as comorbidities are common in people with Down Syndrome (DS). Therefore it is relevant to know whether micronutrient levels in people with DS are also different. This systematic review was designed to review the literature on micronutrient levels in people with DS compared to age and sex-matched controls without DS. We identified sixty nine studies from January 1967 to April 2016 through main electronic medical databases PubMed, Scopus, and Web of knowledge. We carried out meta-analysis of the data on four essential trace elements (Cu, Fe, Se, and Zn), six minerals (Ca, Cl, K, Mg, Na, and P), and five vitamins (vitamin A, B9, B12, D, and E). People with DS showed lower blood levels of Ca (standard mean difference (SMD) = -0.63; 95% confidence interval (CI): -1.16 to -0.09), Se (SMD = -0.99; 95% CI: -1.55 to -0.43), and Zn (SMD = -1.30; 95% CI: -1.75 to -0.84), while red cell levels of Zn (SMD = 1.88; 95% CI: 0.48 to 3.28) and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57) were higher. They had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33) and Na (SMD = 1.04; 95% CI: 0.39 to 1.69). Our findings that micronutrient levels are different in people with DS raise the question whether these differences are related to the different metabolic profiles, the common comorbidities or merely reflect DS.

TÍTULO / TITLE:    - A Comprehensive Diverse ‘-omics’ Approach to Better Understanding the Molecular Pathomechanisms of Down Syndrome.

REVISTA / JOURNAL:    - Brain Sci. 2017 Apr 21;7(4). pii: E44. doi: 10.3390/brainsci7040044.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci7040044

AUTORES / AUTHORS: - Ishihara K; Akiba S

INSTITUCIÓN / INSTITUTION: - Department of Pathological Biochemistry, Division of Pathological Science, Kyoto Pharmaceutical University, 5 Misasagi Nakauchi-cho, Ymashina-ku, Kyoto 607-8414, Japan.   ishihara@mb.kyoto-phu.ac.jp

RESUMEN / SUMMARY: - Diverse ‘-omics’ technologies permit the comprehensive quantitative profiling of a variety of biological molecules. Comparative ‘-omics’ analyses, such as transcriptomics and proteomics, are powerful and useful tools for unraveling the molecular pathomechanisms of various diseases. As enhanced oxidative stress has been demonstrated in humans and mice with Down syndrome (DS), a redox proteomic analysis is useful for understanding how enhanced oxidative stress aggravates the state of individuals with oxidative stress-related disorders. In this review, ‘-omics’ analyses in humans with DS and mouse models of DS are summarized, and the molecular dissection of this syndrome is discussed.

NEUROBIOLOGY - NEUROBIOLOGÍA

TÍTULO / TITLE:    - Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

REVISTA / JOURNAL:    - Physiol Behav. 2017 Aug 1;177:230-241. doi: 10.1016/j.physbeh.2017.05.003. Epub 2017 May 3.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.physbeh.2017.05.003

AUTORES / AUTHORS: - Stringer M; ... Roper RJ;

INSTITUCIÓN / INSTITUTION: - IUPUI, Department of Biology, 723 West Michigan Street, SL 306, Indianapolis, IN 46202-3275, United States.   rjroper@iupui.edu

RESUMEN / SUMMARY: - Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis in

TÍTULO / TITLE:    - Morphological alterations in the hippocampus of the Ts65Dn mouse model for Down Syndrome correlate with structural plasticity markers.

REVISTA / JOURNAL:    - Histol Histopathol. 2017 Apr 4:11894. doi: 10.14670/HH-11-894.

Enlace a la Editora de la Revista http://dx.doi.org/10.14670/HH-11-894

AUTORES / AUTHORS: - Villarroya O; ... Varea E;

INSTITUCIÓN / INSTITUTION: - Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de Valencia, Valencia, España.   emilio.varea@uv.es

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common chromosomal aneuploidy. Although trisomy on chromosome 21 can display variable phenotypes, there is a common feature among all DS individuals: the presence of intellectual disability. This condition is partially attributed to abnormalities found in the hippocampus of individuals with DS and in the murine model for DS, Ts65Dn. To check if all hippocampal areas were equally affected in 4-5 month adult Ts65Dn mice, we analysed the morphology of dentate gyrus granule cells and cornu ammonis pyramidal neurons using Sholl method on Golgi-Cox impregnated neurons. Structural plasticity has been analysed using immunohistochemistry for plasticity molecules followed by densitometric analysis (Brain Derived Neurotrophic Factor (BDNF), Polysialylated form of the Neural Cell Adhesion Molecule (PSA-NCAM) and the Growth Associated Protein 43 (GAP43)). We observed an impairment in the dendritic arborisation of granule cells, but not in the pyramidal neurons in the Ts65Dn mice. When we analysed the expression of molecules related to structural plasticity in trisomic mouse hippocampus, we observed a reduction in the expression of BDNF and PSA-NCAM, and an increment in the expression of GAP43. These alterations were restricted to the regions related to dentate granule cells suggesting an interrelation. Therefore the impairment in dendritic arborisation and molecular plasticity is not a general feature of all Down Syndrome principal neurons. Pharmacological manipulations of the levels of plasticity molecules could provide a way to restore granule cell morphology and function.

TÍTULO / TITLE:    - Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome.

REVISTA / JOURNAL:    - Sci Rep. 2017 Apr 3;7:45561. doi: 10.1038/srep45561.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/srep45561

AUTORES / AUTHORS: - Kazim SF; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurochemistry, and SUNY Downstate/NYSIBR Center for Developmental Neuroscience, New York State Institute for Basic Research (NYSIBR), Staten Island, NY 10314, USA.;The Robert F. Furchgott Center for Neural and Behavioral Scie  

RESUMEN / SUMMARY: - Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3beta) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model.

NEUROLOGY - NEUROLOGÍA

TÍTULO / TITLE:    - Young children with Down syndrome show normal development of circadian rhythms, but poor sleep efficiency: a cross-sectional study across the first 60 months of life.

REVISTA / JOURNAL:    - Sleep Med. 2017 May;33:134-144. doi: 10.1016/j.sleep.2016.12.026. Epub 2017 Feb 10.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.sleep.2016.12.026

AUTORES / AUTHORS: - Fernandez F; .... Edgin EJ

INSTITUCIÓN / INSTITUTION: - Departments of Psychology and Neurology, BIO5 Institute, University of Arizona, Tucson, USA; Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, USA.   FabianF@email.arizona.edu

RESUMEN / SUMMARY: - OBJECTIVES: To evaluate sleep consolidation and circadian activity rhythms in infants and toddlers with Down syndrome (DS) under light and socially entrained conditions within a familiar setting. Given previous human and animal data suggesting intact circadian regulation of melatonin across the day and night, it was hypothesized that behavioral indices of circadian rhythmicity would likewise be intact in the sample with DS. METHODS: A cross-sectional study of 66 infants and young children with DS, aged 5-67 months, and 43 typically developing age-matched controls. Sleep and measures of circadian robustness or timing were quantified using continuous in-home actigraphy recordings performed over seven days. Circadian robustness was quantified via time series analysis of rest-activity patterns. Phase markers of circadian timing were calculated alongside these values. Sleep efficiency was also estimated based on the actigraphy recordings. RESULTS: This study provided further evidence that general sleep quality is poor in infants and toddlers with DS, a population that has sleep apnea prevalence as high as 50% during the preschool years. Despite poor sleep quality, circadian rhythm and phase were preserved in children with DS and displayed similar developmental trajectories in cross-sectional comparisons with a typically developing (TD) cohort. In line with past work, lower sleep efficiency scores were quantified in the group with DS relative to TD children. Infants born with DS exhibited the worst sleep fragmentation; however, in both groups, sleep efficiency and consolidation increased across age. Three circadian phase markers showed that 35% of the recruitment sample with DS was phase-advanced to an earlier morning schedule, suggesting significant within-group variability in the timing of their daily activity rhythms. CONCLUSIONS: Circadian rhythms of wake and sleep are robust in children born with DS. The present results suggest that sleep fragmentation and any result

TÍTULO / TITLE:    - Acute Cerebral Symptoms in a Child with Down Syndrome and Acute Leukemia - What has to be Considered?

REVISTA / JOURNAL:    - Klin Padiatr. 2017 May;229(3):177-179. doi: 10.1055/s-0042-124665. Epub 2017 Apr 4.

Enlace a la Editora de la Revista http://dx.doi.org/10.1055/s-0042-124665

AUTORES / AUTHORS: - Benecke N; et al

INSTITUCIÓN / INSTITUTION: - Klinik und Poliklinik fur Kinder- und Jugendmedizin, Bereich Hamatologie/Onkologie, Medizinische Fakultat der Technischen Universitat Dresden, BRD.  

RESUMEN / SUMMARY: -

OPHTALMOLOGY - OFTALMOLOGÍA

TÍTULO / TITLE:    - Performing corneal crosslinking under local anaesthesia in patients with Down syndrome.

REVISTA / JOURNAL:    - Int Ophthalmol. 2017 Apr 19. doi: 10.1007/s10792-017-0535-1.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10792-017-0535-1

AUTORES / AUTHORS: - Soeters N et al

INSTITUCIÓN / INSTITUTION: - Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, HP E03.136, Heidelberglaan 100, 3508 GX, Utrecht, The Netherlands.  

RESUMEN / SUMMARY: - PURPOSE: To report on the ability to perform corneal crosslinking (CXL) under local anaesthesia for the treatment of keratoconus in patients with Down syndrome. METHODS: Nine eyes of seven patients with both keratoconus and Down syndrome were scheduled for an epithelium-off CXL procedure under local anaesthesia. Exclusion criteria were a corneal thickness under 400 microm and the presence of corneal scars. A standardized clinical decision tool was used to estimate patient cooperation and the likelihood for a successful procedure under local rather than general anaesthesia. RESULTS: In seven eyes, the CXL was completed successfully. The treatment was aborted in two eyes due to insufficient corneal thickness (<400 microm) prior to ultraviolet-A irradiation, even after employing hypoosmolar riboflavin. No adverse events occurred post-operatively, except for one case of delayed epithelial healing (23 days). CONCLUSIONS: With a proper patient selection, CXL under local anaesthesia can be achieved in patients with Down syndrome.

TÍTULO / TITLE:    - Outcomes of Cataract Surgery in Children with Down Syndrome.

REVISTA / JOURNAL:    - J Ophthalmic Vis Res. 2017 Apr-Jun;12(2):243-244. doi: 10.4103/jovr.jovr_212_16.

Enlace a la Editora de la Revista http://dx.doi.org/10.4103/jovr.jovr_212_16

AUTORES / AUTHORS: - Saifee M; et al.

INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.  

RESUMEN / SUMMARY: - Cataract extraction in pediatric patients with Down syndrome does not appear to have a higher rate of surgical complications than does cataract surgery in the general pediatric population.

TÍTULO / TITLE:    - Brain tuberculoma, an unusual cause of stroke in a child with trisomy 21: a case report.

REVISTA / JOURNAL:    - J Med Case Rep. 2017 Apr 18;11(1):114. doi: 10.1186/s13256-017-1258-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13256-017-1258-7

AUTORES / AUTHORS: - Kheir AEM; et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics and Child Health, Faculty of Medicine, University of Khartoum and Soba University Hospital, P.O. Box 102, Khartoum, Sudan.   moneimkheir62@hotmail.com

RESUMEN / SUMMARY: - Tuberculosis remains a public health problem in developing countries and is associated with lethal central nervous system complications. Intracranial tuberculomas occur in 13% of children with neurotuberculosis. Patients with trisomy 21 have an increased risk for stroke, which usually stems from cardiovascular defects. CASE PRESENTATION: We report a case of a 12-year-old Sudanese boy with trisomy 21 who was presented to our hospital with focal convulsions and right-sided weakness. The results of neuroimaging and histopathological examinations were consistent with cerebral tuberculoma. The patient had a good initial response to antituberculosis drugs and steroids. To the best of our knowledge, this is the first case report of multiple brain tuberculomas described in a child with trisomy 21. CONCLUSIONS: Patients with trisomy 21 have an increased risk for stroke. Our patient had an exceptional case of stroke caused by tuberculoma. The present case emphasizes the need to consider tuberculomas in the differential diagnosis of children with neurological symptoms living in areas of high tuberculosis incidence.

PHYSIOTHERAPY - FISIOTERAPIA

TÍTULO / TITLE:    - Short-term motor learning through non-immersive virtual reality task in individuals with down syndrome.

REVISTA / JOURNAL:    - BMC Neurol. 2017 Apr 14;17(1):71. doi: 10.1186/s12883-017-0852-z.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12883-017-0852-z

AUTORES / AUTHORS: - de Mello Monteiro CB; et al.

INSTITUCIÓN / INSTITUTION: - School of Arts, Sciences and Humanities, University of Sao Paulo, Av. Arlindo Bettio, 1000, Ermelino Matarazzo, Sao Paulo, 03828-000, Brazil.  

RESUMEN / SUMMARY: - Down syndrome (DS) has unique physical, motor and cognitive characteristics. Despite cognitive and motor difficulties, there is a possibility of intervention based on the knowledge of motor learning. However, it is important to study the motor learning process in individuals with DS during a virtual reality task to justify the use of virtual reality to organize intervention programs. The aim of this study was to analyze the motor learning process in individuals with DS during a virtual reality task. METHODS: A total of 40 individuals participated in this study, 20 of whom had DS (24 males and 8 females, mean age of 19 years, ranging between 14 and 30 yrs.) and 20 typically developing individuals (TD) who were matched by age and gender to the individuals with DS. To examine this issue, we used software that uses 3D images and reproduced a coincidence-timing task. RESULTS: The results showed that all individuals improved performance in the virtual task, but the individuals with DS that started the task with worse performance showed higher difference from the beginning. Besides that, they were able to retain and transfer the performance with increase of speed of the task. CONCLUSION: Individuals with DS are able to learn movements from virtual tasks, even though the movement time was higher compared to the TD individuals. The results showed that individuals with DS who started with low performance improved coincidence- timing task with virtual objects, but were less accurate than typically developing individuals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02719600 .

TÍTULO / TITLE:    - Leisure Activity and Caregiver Involvement in Middle-Aged and Older Adults With Down Syndrome.

REVISTA / JOURNAL:    - Intellect Dev Disabil. 2017 Apr;55(2):97-109. doi: 10.1352/1934-9556-55.2.97.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1934-9556-55.2.97

AUTORES / AUTHORS: - Mihaila I; et al.

INSTITUCIÓN / INSTITUTION: - Iulia Mihaila and Sigan L. Hartley, University of Wisconsin - Madison.  

RESUMEN / SUMMARY: - The present study examined leisure activity and its association with caregiver involvement (i.e., residence and time spent with primary caregiver) in 62 middle-aged and older adults with Down syndrome (aged 30-53 years). Findings indicated that middle-aged and older adults with Down syndrome frequently participated in social and passive leisure activities, with low participation in physical and mentally stimulating leisure activities. Residence and time spent with primary caregiver were associated with participation in physical leisure activity. The findings suggest a need for support services aimed at increasing opportunities for participating in physical and mentally stimulating leisure activity by middle-aged and older adults with Down syndrome. These support services should partner with primary caregivers in order to best foster participation in physical leisure activity.

TÍTULO / TITLE:    - Physical Activity Patterns in Infants With and Without Down Syndrome.

REVISTA / JOURNAL:    - Pediatr Phys Ther. 2017 May 19. doi: 10.1097/PEP.0000000000000397.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/PEP.0000000000000397

AUTORES / AUTHORS: - Ketcheson L;

INSTITUCIÓN / INSTITUTION: - School of Kinesiology, University of Michigan, Ann Arbor, Michigan.  

RESUMEN / SUMMARY: - PURPOSE: Individuals with Down syndrome (DS) are at greater risk for obesity than their peers who are developing typically. One factor contributing to an early onset of obesity is low levels of physical activity (PA). However, there is little known regarding PA patterns during infancy. METHODS: The purpose of this study was to examine the daily PA patterns in 22 infants developing typically and 11 infants with Down syndrome (aged 1-12 months) using Actigraph GT3X+ (wrist and ankle). RESULTS: No significant differences between groups were identified in PA counts at the ankle. Both groups produced significantly more PA at the wrist than at the ankle and PA counts increased across months in age. CONCLUSION: This study represents an important first step in establishing baseline PA patterns during infancy.

PRENATAL DIAGNOSIS - DIAGNÓSTICO

TÍTULO / TITLE:    - Antepartum management and obstetric outcomes among pregnancies with Down syndrome from diagnosis to delivery.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 Apr 17. doi: 10.1002/pd.5054.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5054

AUTORES / AUTHORS: - Guseh SH Little SE;

INSTITUCIÓN / INSTITUTION: - Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.  

RESUMEN / SUMMARY: - OBJECTIVE: Little is known about the obstetric care of an ongoing pregnancy with trisomy 21. We sought to ascertain an obstetric profile for pregnancies with Down syndrome to help guide prenatal management. METHOD: Pregnancies managed for delivery with trisomy 21 between 2003 and 2014 were analyzed. We reviewed demographic data, diagnostic testing, prenatal surveillance, obstetric outcomes, and placental pathology. T-test, chi-squared test, and Fisher correction were used as indicated. RESULTS: Sixty-eight pregnancies were identified, and four women (5.9%) experienced a loss during the pregnancy. Among the remaining 64 pregnancies, the average gestational age at delivery was 36.9 weeks, growth restriction was present in 12 (17.5%), and major anomalies were present in 51 (75.0%). Delivery was undertaken for non-reassuring fetal surveillance in 35.9% of the pregnancies; 93% of which represented a change from prior reassuring surveillance and 52.6% of which demonstrated histopathologic evidence of placental insufficiency. None among increased maternal age, the presence of an anomaly, or growth restriction were significantly more common in the group with non-reassuring surveillance. CONCLUSION: There are high rates of fetal growth restriction, delivery for non-reassuring fetal status, and evidence of placental insufficiency among affected pregnancies, suggesting a role for antepartum surveillance. © 2017 John Wiley & Sons, Ltd.

TÍTULO / TITLE:    - Building a Progressive-Situational Model of Post-Diagnosis Information Seeking for Parents of Individuals With Down Syndrome.

REVISTA / JOURNAL:    - Glob Qual Nurs Res. 2016 Nov 29;3:2333393616680967. doi: 10.1177/2333393616680967. eCollection 2016

Enlace a la Editora de la Revista http://dx.doi.org/10.1177_2333393616680967

AUTORES / AUTHORS: - Gibson AN;

INSTITUCIÓN / INSTITUTION: - University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.  

RESUMEN / SUMMARY: - This grounded theory study used in-depth, semi-structured interview to examine the information-seeking behaviors of 35 parents of children with Down syndrome. Emergent themes include a progressive pattern of behavior including information overload and avoidance, passive attention, and active information seeking; varying preferences between tacit and explicit information at different stages; and selection of information channels and sources that varied based on personal and situational constraints. Based on the findings, the author proposes a progressive model of health information seeking and a framework for using this model to collect data in practice. The author also discusses the practical and theoretical implications of a responsive, progressive approach to understanding parents’ health information-seeking behavior.

TÍTULO / TITLE:    - The outcomes and prognostic factors of fetal hydrothorax associated with trisomy 21.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 May 11. doi: 10.1002/pd.5066.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5066

AUTORES / AUTHORS: - Yumoto Y; et al.

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Kyushu University Hospital, Kyushu University, Fukuoka, Japan.  

RESUMEN / SUMMARY: - OBJECTIVES: To determine the characteristics, outcomes, and prognostic factors of fetal hydrothorax (FHT) with trisomy 21. METHODS: A nationwide survey was conducted on FHT fetuses with trisomy 21 delivered after 22 weeks’ gestation between January 2007 and December 2011 at perinatal centers. RESULTS: The 91 cases of FHT with trisomy 21 included 28 (30.8%) diagnosed in utero and 63 (69.2%) diagnosed after birth. The natural remission rate was 6.6% (6/91). Thoracoamniotic shunting was performed in 14.3% (13/91) of cases. The survival rates of the hydropic, nonhydropic, and total cases were 47.0% (31/66), 84.0% (21/25), and 57.1% (52/91), respectively. The crude odds ratio for death was 8.2 (p = 0.003) for fetuses diagnosed at 26-30 weeks of gestational age (vs >/=30 weeks), 5.9 (p = 0.003) for hydrops, 4.0 (p = 0.04) for bilateral pleural effusion, 0.68 (p = 0.42) for associated cardiovascular anomalies, and 2.1 (p = 0.26) for thoracoamniotic shunting (vs no fetal therapy). CONCLUSIONS: The prognosis of FHT with trisomy 21 was not very poor, but it was still worse than that of primary FHT. Hydrops, an early gestational age at the diagnosis and bilateral effusion, but not associated anomalies, were risk factors for death. Fetal therapy showed no survival benefit for FHT with trisomy 21.

TÍTULO / TITLE:    - Aiding risk information learning through simulated experience (ARISE): Using simulated outcomes to improve understanding of conditional probabilities in prenatal Down syndrome screening.

REVISTA / JOURNAL:    - Patient Educ Couns. 2017 Apr 26. pii: S0738-3991(17)30250-1. doi: 10.1016/j.pec.2017.04.016.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.pec.2017.04.016

AUTORES / AUTHORS: - Wegier P; Shaffer VA

INSTITUCIÓN / INSTITUTION: - Department of Health Sciences, University of Missouri, Columbia, MO, USA.   wegierp@health.missouri.edu

RESUMEN / SUMMARY: - To determine whether the use of simulated experiences to communicate statistical information can improve an individual’s understanding of conditional probabilities-specifically the positive predictive value (PPV) of prenatal screening tests for Down syndrome. METHODS: In Experiment 1 (N=64) and Experiment 2 (N=180) participants were asked to estimate the PPV of a prenatal screening test for Down syndrome based on either (1) explicit statistics regarding the prevalence of Down syndrome and the sensitivity and specificity of a prenatal screening test for Down syndrome, or (2) experiencing up to 5000 simulated test results over a short time. RESULTS: Participants’ estimates of the PPV were more accurate when they had learned via simulated experiences (79% accuracy) compared with estimates based on explicitly described statistics (14%). Participants in the simulated experience condition also reported decreased interest in screening and decreased concern with a positive test result. CONCLUSION: Simulated experiences improve PPV estimates, compared to estimates derived from explicitly provided statistics, while also shifting attitudes away from screening. PRACTICE IMPLICATIONS: The use of simulated experiences may prove to be simple but powerful tool to communicate complex statistical information to patients in medical decision making situations.

TÍTULO / TITLE:    - First trimester ultrasound screening for trisomy 21 based on maternal age, fetal nuchal translucency and different methods of ductus venosus assessment.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 May 11. doi: 10.1002/pd.5065.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5065

AUTORES / AUTHORS: - Wagner P; et al

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, University of Tuebingen, Germany.  

RESUMEN / SUMMARY: - To examine whether combining the dichotomous assessment of the a-wave and the Ductus venosus (DV) PIV measurement improves first-trimester-screening performance. METHODS: Retrospective study performed at the University Hospital of Tuebingen based on singleton pregnancies that underwent first-trimester-screening including DV flow assessment. In each case, the risk of trisomy 21 was calculated based on maternal age, fetal NT, and DV flow either as dichotomous classification of the a-wave, as measurement of the DV PIV, or both. RESULTS: There were 5280 euploid fetuses and 127 fetuses with trisomy 21. The DV a-wave was reversed in 2.3% and 66.1% in the euploid and trisomy 21 cases, respectively. The DV PIV measurements were above the 95th percentile in 8.3% and 77.2% the euploid and trisomy 21 cases, respectively. For a FPR of 3%, DR for trisomy 21 based on maternal age, fetal NT and DV flow is about 87% irrespective of whether DV is examined as a continuous or dichotomous variable. The combination of both resulted in a small decrease at 3% FPR. CONCLUSION: Assessment of the DV a-wave and the DV PIV result in similar DRs. Combining these two approaches does not appear to improve their individual screening performance.

TÍTULO / TITLE:    - Impact on spina bifida screening of shifting prenatal Down syndrome maternal serum screening from the second trimester to the first.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 Apr 28. doi: 10.1002/pd.5064.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5064

AUTORES / AUTHORS: - Spaggiari E... Muller F et al

INSTITUCIÓN / INSTITUTION: - Department of Biochemistry-Hormonology, Robert Debre Hospital, AP-HP, Paris, France.;Secretary and President of the French Association of the biologists accredited for maternal serum Down syndrome screening. Study Group listed in the append  

RESUMEN / SUMMARY: - Shifting screening for trisomy 21 to the first trimester has resulted in the loss of MSAFP screening for spina bifida. The aim of this study was to study the impact on open spina bifida prenatal screening. STUDY DESIGN: We reviewed prenatally diagnosed cases of spina bifida over three years: 2009 (only second-trimester screening, MSM2T), 2010 (transient period) and 2011 (majority first-trimester screening, MSM1T). Cases were assigned to three groups based on maternal serum markers (MSM2T, MSM1T and “not performed”). Gestational age at diagnosis of spina bifida was compared between these three groups and between the years 2009 and 2011. RESULTS: Median gestational ages at diagnosis of the 742 spina bifida cases between the three groups were 22 weeks [18+6 -23], 22+1 weeks [21+3 -23] and 21+4 weeks [14+1 -23], respectively (P < 0.005). The diagnosis was made at 14-20 weeks in 34.7% for MSM2T group versus 8.5% for MSM1T (P < 0.001). Spina bifida diagnosis at 14-20 weeks declined from 38.8% in 2009 to 13.3% in 2011 (P < 0.001). CONCLUSION: Loss of MSAFP had a tangible effect on the gestational age at diagnosis of spina bifida, and resulted in a decrease of 25% of cases of spina bifida detected before 20 weeks.

TÍTULO / TITLE:    - Noninvasive Prenatal Detection of Trisomy 21 by Targeted Semiconductor Sequencing: A Technical Feasibility Study.

REVISTA / JOURNAL:    - Fetal Diagn Ther. 2017 May 17. doi: 10.1159/000460248.

Enlace a la Editora de la Revista http://dx.doi.org/10.1159/000460248

AUTORES / AUTHORS: - Xi Y; et al

INSTITUCIÓN / INSTITUTION: - Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.  

RESUMEN / SUMMARY: - To develop an alternate noninvasive prenatal testing method for the assessment of trisomy 21 (T21) using a targeted semiconductor sequencing approach. METHODS: A customized AmpliSeq panel was designed with 1,067 primer pairs targeting specific regions on chromosomes 21, 18, 13, and others. A total of 235 samples, including 30 affected with T21, were sequenced with an Ion Torrent Proton sequencer, and a method was developed for assessing the probability of fetal aneuploidy via derivation of a risk score. RESULTS: Application of the derived risk score yields a bimodal distribution, with the affected samples clustering near 1.0 and the unaffected near 0. For a risk score cutoff of 0.345, above which all would be considered at “high risk,” all 30 T21-positive pregnancies were correctly predicted to be affected, and 199 of the 205 non-T21 samples were correctly predicted. The average hands-on time spent on library preparation and sequencing was 19 h in total, and the average number of reads of sequence obtained was 3.75 million per sample. CONCLUSION: With the described targeted sequencing approach on the semiconductor platform using a custom-designed library and a probabilistic statistical approach, we have demonstrated the feasibility of an alternate method of assessment for fetal T21.

TÍTULO / TITLE:    - Who is and isn’t having babies with Down syndrome in western Sydney: a ten year hospital cohort study.

REVISTA / JOURNAL:    - Aust N Z J Obstet Gynaecol. 2017 Apr;57(2):146-151. doi: 10.1111/ajo.12617. Epub 2017 Mar 29.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/ajo.12617

AUTORES / AUTHORS: - Moses RM; et al.

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, Westmead Hospital, Sydney, New South Wales, Australia.  

RESUMEN / SUMMARY: - Screening for Down syndrome (DS) is a key component of antenatal care, recommended to be universally offered to women irrespective of age or background. Despite this, the diagnosis of DS is often not made until the neonatal period. AIMS: To retrospectively describe and compare the differences in populations with an antenatal diagnosis (AD) and neonatal diagnosis (ND) of DS and to explore why an antenatal diagnosis was not made. MATERIALS AND METHODS: The cohorts were women cared for at Westmead Hospital whose pregnancy received a diagnosis of DS between 2006 and 2015. The demographic variables of the AD and ND cohorts were examined and reasons why an antenatal diagnosis was not made in the ND cohort were analysed. RESULTS: There were 127 diagnoses of DS in the 10-year period, of which 41% were in the ND cohort (n = 52) and 59% in the AD (n = 75). Declaring a religious affiliation rather than Nil Religion was significantly more common in the ND cohort (88.5%) and especially the ND sub-cohort who declined DS screening/testing (95.8%) than the AD cohort (72%, P < 0.05). Women who were not offered screening were significantly younger (P < 0.001) than those who were, with 69% and 20% being TÍTULO / TITLE:    - Prenatal Phenotype of Down Syndrome Using Three-Dimensional Virtual Reality.

REVISTA / JOURNAL:    - J Obstet Gynaecol Can. 2017 May 5. pii: S1701-2163(17)30255-4. doi: 10.1016/j.jogc.2017.03.100.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jogc.2017.03.100

AUTORES / AUTHORS: - Werner H;... Araujo Junior E;

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics, Paulista School of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.   araujojred@terra.com.br

RESUMEN / SUMMARY: - Down syndrome is a chromosomal abnormality characterized by an additional acrocentric chromosome, resulting in an aneuploid number of 47 chromosomes (trisomy 21). Fetal face phenotype of Down syndrome is typical in the second trimester and characterized by plane face and a big and protruding tongue. CASE: We present a case of Down syndrome at 29 weeks of gestation in which the fetal face was created using 3-D virtual reality model from 3-D ultrasound scan data. CONCLUSION: A 3-D virtual model from 3-D ultrasound or magnetic resonance imaging scan data allowed an immersive real environment, improving the understanding of fetal congenital anomalies by the parents and the medical team.

TÍTULO / TITLE:    - Proteomic profile of serum of pregnant women carring a fetus with Down syndrome using nano uplc Q-tof ms/ms technology.

REVISTA / JOURNAL:    - J Matern Fetal Neonatal Med. 2017 May 3:1-7. doi: 10.1080/14767058.2017.1319923.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/14767058.2017.1319923

AUTORES / AUTHORS: - Lopez Uriarte GA; et al.

INSTITUCIÓN / INSTITUTION: - a Departamento de Genetica, Facultad de Medicina , Hospital Universitario, Universidad Autonoma de Nuevo Leon , Monterrey , Mexico.  

RESUMEN / SUMMARY: - Prenatal diagnosis of Down syndrome (DS) is based on the calculated risk of maternal age, biochemical and ultrasonographic markers and recently by cfDNA. Differences in proteomic profiles may give an opportunity to find new biomarkers. OBJECTIVE: Characterize proteome of serum of mothers carrying DS fetus. MATERIAL AND METHODS: Blood serum samples of three groups of women were obtained, (a) 10 non-pregnant, (b) 10 pregnant with healthy fetus by ultrasound evaluation, (c) nine pregnant with DS fetus. Sample preparation was as follows: Albumin/IgG depletion, desalting, and trypsin digestion; the process was performed in nanoUPLC MS/MS. Data analysis was made with Mass Lynx 4.1 and ProteinLynx Global Server 3.0, peptide and protein recognition by MASCOT algorithm and UNIPROT-Swissprot database. RESULTS: Each group showed different protein profiles. Some proteins were shared between groups. Only sera from pregnant women showed proteins related to immune and clot pathways. Mothers with DS fetus had 42 specific proteins. CONCLUSIONS: We found a different serum protein profile in mothers carrying DS fetuses that do not reflect expression of genes in the extra chromosome. Further studies will be necessary to establish the role of these proteins in aneuploid fetus and analyze their possible use as potential biomarkers.

TÍTULO / TITLE:    - Detection Rate and Sonographic Signs of Trisomy 21 Fetuses at 14-17 Weeks of Gestation.

REVISTA / JOURNAL:    - Isr Med Assoc J. 2017 Jan;19(1):8-12.

AUTORES / AUTHORS: - Bronshtein E; et al.

INSTITUCIÓN / INSTITUTION: - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.  

RESUMEN / SUMMARY: - Early prenatal ultrasound is an important part of prenatal screening in Israel. No studies have described the rate of trisomy 21 [T21] identification at 14-17 weeks gestation. OBJECTIVES: To describe the rate of T21 identification by transvaginal sonograms (TVS) at 14-17 weeks gestation. METHODS: We conducted a historical prospective study. Since 1986, early TVS of 72,000 fetuses at 14-17 weeks gestation have been prospectively recorded together with prenatal screening data at a private ultrasound center (AL-KOL, Haifa). We calculated the fraction of T21 cases by dividing the total number of cases with abnormal sonographic findings by the total number of diagnosed T21 cases. We also examined the percentage of verified T21 cases that had completely normal prenatal screening tests prior to the early prenatal TVS, thus revealing the contribution of this examination to the existing prenatal screening. Fisher’s exact test was used to calculate odds ratios for each sonographic marker. RESULTS: Of 137 T21 fetuses, 123 had sonographic markers on early TVS, yielding a prediction capability of at least 89.87%. Of all T21 cases, 14% had completely normal nuchal translucency/first-trimester screening prior to the abnormal 14-17 week TVS findings. Isolated abnormal sonographic findings, which were found to increase the risk for T21, were common atrioventricular septal canal (odds ratio 88.88), duodenal atresia (OR 88.23), nuchal edema (OR 39.14), and hydrocephalus (OR 15.78). Fetal hydronephrosis/pyelectasis was non-significant when isolated (OR 1), and cardiac echogenic focus was associated with a decreased risk (OR 0.13). CONCLUSIONS: Early prenatal TVS at 14-17 weeks may identify almost 90% of T21 and adds 14% to the identification rate at the first-trimester screening.

TÍTULO / TITLE:    - Congenital Absence of Salivary Glands in Fetuses with Trisomy 21.

REVISTA / JOURNAL:    - Isr Med Assoc J. 2017 Jan;19(1):12-14.

AUTORES / AUTHORS: - Odeh M;Bronshtein M; Bornstein J;

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Israel.; Galilee Faculty of Medicine, Bar Ilan University, Safed. University of Haifa, Haifa, Israel.  

RESUMEN / SUMMARY: - The congenital absence of salivary glands has been reported in children but never in fetuses with trisomy 21. OBJECTIVES: To determine whether the congenital absence of salivary glands can be detected prenatally between 13 and 16 weeks of gestation in normal and trisomy 21 fetuses using transvaginal ultrasound. METHODS: We performed a retrospective analysis of recordings of normal and trisomy 21 fetuses. Inclusion criteria were a single viable fetus and good visualization of the anatomic area of the salivary glands on both sides of the fetal face. All videos were reviewed by one examiner who reported the presence or absence of one or more salivary glands and was blinded to the fetal karyotype. RESULTS: Of the 45 videos reviewed, 4 were excluded from the study: namely, a non-viable fetus, twin pregnancy, and in 2 there was unsatisfactory visualization of the anatomic area of the salivary glands. Of the remaining 41 fetuses, 24 had trisomy 21 and 17 were normal. In the trisomy 21 fetuses, 8 (33.3%) had congenital absence of one or more salivary glands compared to 1 of 17 normal fetuses (5.9%) (P < 0.05). CONCLUSIONS: Congenital absence of the salivary glands has a high specificity but low sensitivity for detecting trisomy 21 fetuses.

TÍTULO / TITLE:    - Development and evaluation of training resources to prepare health professionals for counselling pregnant women about non-invasive prenatal testing for Down syndrome: a mixed methods study.

REVISTA / JOURNAL:    - BMC Pregnancy Childbirth. 2017 Apr 27;17(1):132. doi: 10.1186/s12884-017-1315-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12884-017-1315-7

AUTORES / AUTHORS: - Oxenford K; et al

INSTITUCIÓN / INSTITUTION: - Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London, UK.  

RESUMEN / SUMMARY: - The availability of non-invasive prenatal testing (NIPT) for aneuploidies is expanding rapidly throughout the world. Training health professionals to offer NIPT in a way that supports informed choice is essential for implementation. The aim of this study was to develop and evaluate a training package for health professionals to support the introduction of NIPT into clinical practice. METHODS: Training on NIPT was offered to health professionals, primarily midwives, involved in Down syndrome screening and testing in eight hospitals located in England and Scotland as part of a research study evaluating the implementation of NIPT in the UK National Health Service. Training was evaluated using a mixed methods approach that included quantitative questionnaires at three time points and post-training qualitative interviews. The questionnaires measured confidence, self-perceived knowledge and actual knowledge about NIPT for Down syndrome. Interviews explored opinions about the training and experiences of offering NIPT. RESULTS: The training provided to the health professionals was found to positively impact on their confidence in discussing NIPT with women in their clinic, and both their perceived and actual knowledge and understanding of NIPT was improved. Knowledge remained weak in four areas; cell-free fetal DNA levels increase with gestation; turnaround time for NIPT results; cell-free fetal DNA is placental in origin; and NIPT false positive rate. CONCLUSIONS: Training materials, including a lesson plan, PowerPoint presentation and written factsheet on NIPT, have been developed and evaluated for use in educating midwives and supporting the introduction of NIPT. Implementation of training should include a greater focus on the areas where knowledge remained low. Some groups of midwives will need additional training or support to optimise their confidence in discussing NIPT with women.

TÍTULO / TITLE:    - The rate of invasive testing for trisomy 21 is reduced after implementation of NIPT.

REVISTA / JOURNAL:    - Dan Med J. 2017 Apr;64(4). pii: A5359.

AUTORES / AUTHORS: - Bjerregaard L; et al.

INSTITUCIÓN / INSTITUTION: -   louise.bjerregaard1202@gmail.com

RESUMEN / SUMMARY: - The non-invasive prenatal test (NIPT) was introduced in the North Denmark Region in March 2013. NIPT is offered as an alternative to invasive tests if the combined first trimester risk of trisomy 21 (T21) is >/= 1:300. The purpose of this study was to investigate the effect of NIPT implementation among high-risk pregnancies in a region with existing first-trimester combined screening for T21. The primary objective was to examine the effect on the invasive testing rate. METHODS: This was a retrospective observational study including high-risk singleton pregnancies in the North Denmark Region. The women were included in two periods, i.e. before and after the implementation of NIPT, respectively. Group 1 (before NIPT): n = 253 and Group 2 (after NIPT): n = 302. RESULTS: After NIPT implementation, the invasive testing rate fell from 70% to 48% (p< 0.01), and the number of high-risk women refusing further testing dropped from 26% to 3% (p < 0.01). NIPT successfully detected four cases of T21; however, two out of three sex-chromosomal abnormalities were false positives. No false negative NIPT results were revealed in this study. CONCLUSIONS: In the North Denmark Region, the implementation of NIPT in high-risk pregnancies significantly reduced the rate of invasive testing. However, the proportion of high-risk women who opted for prenatal tests increased as the majority of women who previously refused further testing now opted for the NIPT. FUNDING: none. TRIAL

TÍTULO / TITLE:    - Massively Parallel Sequencing (MPS) of Cell-Free Fetal DNA (cffDNA) for Trisomies 21, 18, and 13 in Twin Pregnancies.

REVISTA / JOURNAL:    - Twin Res Hum Genet. 2017 Jun;20(3):242-249. doi: 10.1017/thg.2017.23. Epub 2017 May 9.

Enlace a la Editora de la Revista http://dx.doi.org/10.1017/thg.2017.23

AUTORES / AUTHORS: - Du E; et al

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology,Zhongnan Hospital of Wuhan University,Wuhan,China.  

RESUMEN / SUMMARY: - Massively parallel sequencing (MPS) technology has become increasingly available and has been widely used to screen for trisomies 21, 18, and 13 in singleton pregnancies. This study assessed the performance of MPS testing of cell-free fetal DNA (cffDNA) from maternal plasma for trisomies 21, 18, and 13 in twin pregnancies. Ninety-two women with twin pregnancies were recruited. The results were identified through karyotypes of amniocentesis or clinical examination and follow-up of the neonates. Fluorescent in-situ hybridization was used to examine the placentas postnatally in cases of false-positive results. The fetuses with autosomal trisomy 21 (n = 2) and trisomy 15 (n = 1) were successfully detected via MPS testing of cffDNA. There was one false-positive for trisomy 13 (n = 1), and fluorescence in-situ hybridization (FISH) identified confined placental mosaicism in this case. For twin pregnancies undergoing second-trimester screening for trisomy, MPS testing of cffDNA is feasible and can enhance the diagnostic spectrum of non-invasive prenatal testing, which could effectively reduce invasive prenatal diagnostic methods. In addition to screening for trisomy 21, 18, and 13 by cffDNA, MPS can detect fetal additional autosomal trisomy. False-positive results cannot completely exclude confined placental mosaicism.

TÍTULO / TITLE:    - Incorporating thyroid markers in Down syndrome screening protocols.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 May;37(5):510-514. doi: 10.1002/pd.5047. Epub 2017 Apr 24.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5047

AUTORES / AUTHORS: - Dhaifalah I et al.

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, Columbia University Medical Centre, New York, NY, USA.  

RESUMEN / SUMMARY: - The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. METHODS: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. RESULTS: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. CONCLUSIONS: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost.

PSYCHIATRY - PSIQUIATRÍA

TÍTULO / TITLE:    - The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and Practice Effects.

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 May;122(3):215-234. doi: 10.1352/1944-7558-122.3.215.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.3.215

AUTORES / AUTHORS: - Edgin JO;et al.

INSTITUCIÓN / INSTITUTION: - Jamie O. Edgin and Payal Anand, University of Arizona;  

RESUMEN / SUMMARY: - A multisite study investigated the test-retest reliability and practice effects of a battery of assessments to measure neurocognitive function in individuals with Down syndrome (DS). The study aimed to establish the appropriateness of these measures as potential endpoints for clinical trials. Neurocognitive tasks and parent report measures comprising the Arizona Cognitive Test Battery (ACTB) were administered to 54 young participants with DS (7-20 years of age) with mild to moderate levels of intellectual disability in an initial baseline evaluation and a follow-up assessment 3 months later. Although revisions to ACTB measures are indicated, results demonstrate adequate levels of reliability and resistance to practice effects for some measures. The ACTB offers viable options for repeated testing of memory, motor planning, behavioral regulation, and attention. Alternative measures of executive functioning are required.

TÍTULO / TITLE:    - Brief Report: Contrasting Profiles of Everyday Executive Functioning in Smith-Magenis Syndrome and Down Syndrome.

REVISTA / JOURNAL:    - J Autism Dev Disord. 2017 May 12. doi: 10.1007/s10803-017-3140-2.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10803-017-3140-2

AUTORES / AUTHORS: - Wilde L; Oliver C

INSTITUCIÓN / INSTITUTION: - Cerebra Centre for Neurodevelopmental Disorders, School of Psychology, University of Birmingham, Birmingham, B15 2TT, UK.   l.v.wilde@bham.ac.uk

RESUMEN / SUMMARY: - Everyday executive function (EF) was examined in Smith-Magenis syndrome (SMS), associated with high risk of behaviour disorder, and Down syndrome (DS), associated with relatively low risk of behaviour disorder. Caregivers of 13 children with SMS and 17 with DS rated everyday EF using the Behavioral Rating Inventory of Executive Functioning-Preschool. Greater everyday EF deficits relative to adaptive ability were evident in SMS than in DS. The SMS profile of everyday EF abilities was relatively uniform; in DS emotional control strengths and working memory weaknesses were evident. Findings implicate broad everyday EF difficulties in SMS compared to DS, corresponding with increased rates of behaviour disorder in SMS. Findings further suggest that everyday EF profiles may, in part, be syndrome related.

TÍTULO / TITLE:    - Acute Regression in Young People with Down Syndrome.

REVISTA / JOURNAL:    - Brain Sci. 2017 May 27;7(6). pii: E57. doi: 10.3390/brainsci7060057.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci7060057

AUTORES / AUTHORS: - Mircher C; et al

INSTITUCIÓN / INSTITUTION: - Jerome Lejeune Institute, Paris 75015, France   clotilde.mircher@institutlejeune.org

RESUMEN / SUMMARY: - Abstract: Adolescents and young adults with Down syndrome (DS) can present a rapid regression with loss of independence and daily skills. Causes of regression are unknown and treatment is most of the time symptomatic. We did a retrospective cohort study of regression cases: patients were born between 1959 and 2000, and were followed from 1984 to now. We found 30 DS patients aged 11 to 30 years old with history of regression. Regression occurred regardless of the cognitive level (severe, moderate, or mild intellectual disability (ID)). Patients presented psychiatric symptoms (catatonia, depression, delusions, stereotypies, etc.), partial or total loss of independence in activities of daily living (dressing, toilet, meals, and continence), language impairment (silence, whispered voice, etc.), and loss of academic skills. All patients experienced severe emotional stress prior to regression, which may be considered the trigger. Partial or total recovery was observed for about 50% of them. In our cohort, girls were more frequently affected than boys (64%). Neurobiological hypotheses are discussed as well as preventative and therapeutic approaches.

TÍTULO / TITLE:    - Emotion Recognition in Adolescents with Down Syndrome: A Nonverbal Approach.

REVISTA / JOURNAL:    - Brain Sci. 2017 May 23;7(6). pii: E55. doi: 10.3390/brainsci7060055.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci7060055

AUTORES / AUTHORS: - Pochon R; et al.

INSTITUCIÓN / INSTITUTION: - Cognition, Health and Socialization Laboratory, Higher School of Teaching and Education, University of Reims Champagne-Ardenne, 51097 Reims, France.   regis.pochon@univ-reims.fr

RESUMEN / SUMMARY: - Several studies have reported that persons with Down syndrome (DS) have difficulties recognizing emotions; however, there is insufficient research to prove that a deficit of emotional knowledge exists in DS. The aim of this study was to evaluate the recognition of emotional facial expressions without making use of emotional vocabulary, given the language problems known to be associated with this syndrome. The ability to recognize six emotions was assessed in 24 adolescents with DS. Their performance was compared to that of 24 typically developing children with the same nonverbal-developmental age, as assessed by Raven’s Progressive Matrices. Analysis of the results revealed no global difference; only marginal differences in the recognition of different emotions appeared. Study of the developmental trajectories revealed a developmental difference: the nonverbal reasoning level assessed by Raven’s matrices did not predict success on the experimental tasks in the DS group, contrary to the typically developing group. These results do not corroborate the hypothesis that there is an emotional knowledge deficit in DS and emphasize the importance of using dynamic, strictly nonverbal tasks in populations with language disorders.

QUALITY OF LIFE - CALIDAD DE VIDA

TÍTULO / TITLE:    - Corrigendum to “Having a son or daughter with Down syndrome: Perspectives from mothers and fathers. Am J Med Genet Part A 155:2335-2347.”

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 May;173(5):1453. doi: 10.1002/ajmg.a.38185. Epub 2017 Feb 16.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38185

AUTORES / AUTHORS: - Skotko BG;

INSTITUCIÓN / INSTITUTION: - Division of Medical Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.  

RESUMEN / SUMMARY: -

TÍTULO / TITLE:    - Neonatal characteristics and perinatal complications in neonates with Down syndrome.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 May;173(5):1279-1286. doi: 10.1002/ajmg.a.38165. Epub 2017 Apr 6.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38165

AUTORES / AUTHORS: - Ergaz-Shaltiel Z;... Tenenbaum A

INSTITUCIÓN / INSTITUTION: - Down Syndrome Center, Hadassah Medical Center, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.  

RESUMEN / SUMMARY: - The annual rate of Down syndrome (DS) births in Jerusalem is stable, regardless of prenatal screening, and diagnostic measures. We aimed to evaluate our historical cohort for obstetrical characteristics and the neonatal course and complications. We reviewed computerized medical files of neonates with the diagnosis of DS born in the four main hospitals in Jerusalem between the years 2000 and 2010 and evaluated for maternal history and primary neonatal hospitalization. A total of 403 neonates were diagnosed with DS. The average maternal age was 35.6 years, 73% were born via spontaneous vaginal delivery. In all gestational ages, the mean birth weight and head circumference percentiles were significantly lower than the general population (P < 0.001 for both) and at each week the HC percentile was lower than the weight percentile (P < 0.0001), worse among males. Mortality during the primary hospitalization was 3.7%. The most common anomalies were cardiac (79%) with either congenital defects or functional abnormalities, neither influenced the length of hospitalization. The main reasons for prolonged hospitalization were prematurity and anomalies of other (non-cardiac) organs. Common perinatal complications included respiratory failure or need for oxygen supplementation (32%), hyperbilirubinemia (23%), sepsis (6.4%), and feeding difficulties (13%). About 84% were fed by human milk; of those, two thirds were exclusively breast-fed and one third were supplemented with infant formula. In conclusion, infants with DS were small for gestational age with relatively reduced head circumference. Despite the increased rate of congenital anomalies and perinatal complications, most infants were discharged home in good medical condition and were exclusively breastfed.

TÍTULO / TITLE:    - Employment and choice-making for adults with intellectual disability, autism, and down syndrome.

REVISTA / JOURNAL:    - Res Dev Disabil. 2017 Jun;65:23-34. doi: 10.1016/j.ridd.2017.04.004. Epub 2017 Apr 23.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2017.04.004

AUTORES / AUTHORS: - Bush KL;

INSTITUCIÓN / INSTITUTION: - The Ohio State University Nisonger Center, 1581 Dodd Dr., Columbus, OH 43210, United States.   Bush.415@osu.edu

RESUMEN / SUMMARY: - Adults with disabilities are employed at a significantly lower rate than adults without disabilities. Of adults with disabilities in the workforce, more individuals work in a facility setting rather than a community setting, despite efforts to improve community inclusion. Choice-making has been proposed as a predictive factor for employment for individuals with disabilities. AIMS: The purpose of this research was to examine the current state of employment for three groups of adults with intellectual disability (ID): individuals with autism spectrum disorder (ASD), individuals with Down syndrome (DS), and individuals with idiopathic ID. Choice-making and its relation to improved employment outcomes was explored. METHODS: This study used National Core Indicator’s Adult Consumer Survey datasets from years 2011-2012 and 2012-2013. Factor analyses revealed latent variables from six choice-making questions in the Adult Consumer Survey. Ordinal logistic regression was used to identify factors related to employment status. RESULTS: Adults with DS had the highest rates of paid community jobs, but adults with ID had the highest rates of choice-making. ID severity level and short-term choice-making had the greatest effects on employment status in all three groups. CONCLUSIONS: Employment rates remain low despite national efforts to find jobs for people with disabilities. Choice-making is a unique factor that was found to be associated with employment status and provides a target for interventions to increase employability.

TÍTULO / TITLE:    - Acute Regression in Young People with Down Syndrome.

REVISTA / JOURNAL:    - Brain Sci. 2017 May 27;7(6). pii: E57. doi: 10.3390/brainsci7060057.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci7060057

AUTORES / AUTHORS: - Mircher C; et al

INSTITUCIÓN / INSTITUTION: - erome Lejeune Institute, Paris 75015, France.   clotilde.mircher@institutlejeune.org

RESUMEN / SUMMARY: - Adolescents and young adults with Down syndrome (DS) can present a rapid regression with loss of independence and daily skills. Causes of regression are unknown and treatment is most of the time symptomatic. We did a retrospective cohort study of regression cases: patients were born between 1959 and 2000, and were followed from 1984 to now. We found 30 DS patients aged 11 to 30 years old with history of regression. Regression occurred regardless of the cognitive level (severe, moderate, or mild intellectual disability (ID)). Patients presented psychiatric symptoms (catatonia, depression, delusions, stereotypies, etc.), partial or total loss of independence in activities of daily living (dressing, toilet, meals, and continence), language impairment (silence, whispered voice, etc.), and loss of academic skills. All patients experienced severe emotional stress prior to regression, which may be considered the trigger. Partial or total recovery was observed for about 50% of them. In our cohort, girls were more frequently affected than boys (64%). Neurobiological hypotheses are discussed as well as preventative and therapeutic approaches.

TÍTULO / TITLE:    - Raising a child with Down’s syndrome: perspectives from South African urban care-givers.

REVISTA / JOURNAL:    - Afr Health Sci. 2016 Dec;16(4):929-935. doi: 10.4314/ahs.v16i4.7.

Enlace a la Editora de la Revista http://dx.doi.org/10.4314/ahs.v16i4.7

AUTORES / AUTHORS: - Barr MD; et al.

INSTITUCIÓN / INSTITUTION: - University of KwaZulu-Natal (Westville Campus), South Africa.  

RESUMEN / SUMMARY: - This study addresses a gap from a South African urban perspective on the knowledge and emotional responses of caregivers with children diagnosed with Down’s syndrome (DS). The study is an initial step towards informing health professionals who adopt a biopsychosocial approach, in an effort to improve interventions for both caregivers and children. METHODS: A simple descriptive survey was utilized with 57 participants who were caregivers of children with DS. Data was analyzed descriptively using the Statistical Package for Social Scientists (SPSS) (version 21). RESULTS: The caregivers’ initial reactions when discovering that the child had DS included shock, sadness and anxiety. When considering the etiology of Down’s syndrome, findings reflected that caregivers understood DS as a medical condition relating to chromosomal abnormalities rather than attribution of the syndrome to a fault of their own. Despite the immediate reactions, the caregivers’ initial emotions toward the child rather than the situation were positive and unchanged by the subsequent challenges in caring for the child. The caregivers indicated feelings of love toward the child notwithstanding the diagnosis. CONCLUSION: This study allowed for the subjective experience, perceptions and attitudes of caregivers to be investigated, and raised further questions into the deeper meanings and experiences of caregivers towards assisting practitioners in understanding the dynamics surrounding care-giving that may influence holistic interventions.

TÍTULO / TITLE:    - Rising infant mortality in down syndrome in Chile from 1997 to 2013.

REVISTA / JOURNAL:    - Rev Med Chil. 2016 Nov;144(11):1432-1439. doi: 10.4067/S0034-98872016001100009.

Enlace a la Editora de la Revista http://dx.doi.org/10.4067/S0034-98872016001100009

AUTORES / AUTHORS: - Donoso E; Vera C

INSTITUCIÓN / INSTITUTION: - Division de Obstetricia y Ginecologia, Unidad de Medicina Basada en la Evidencia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile.  

RESUMEN / SUMMARY: - Down syndrome (DS) is associated with higher child mortality especially due to cardiac malformations. AIM: To describe the trend in Chilean infant mortality in DS in the period 1997-2013 as compared to the general population without DS. MATERIAL AND METHODS: Raw data on infant deaths were extracted from the yearbooks of vital statistics of the National Institute of Statistics. The mortality risk associated to DS, relative to population without DS was estimated. RESULTS: There were 456 deaths in infants with DS during the study period (59 early neonatal deaths, 70 late neonatal deaths and 327 post-neonatal deaths). The trend in infant mortality rate in DS was ascending (r: 0.53, p = 0.03), with an average annual percentage change of 4.6% (95% confidence interval (CI) 0.4-9.0%; p < 0.01). Compared to the population without DS, the risk of early neonatal death was lower in DS (Odds ratio (OR) 0.14, 95% CI 0.11-0.19; p< 0.01) whereas the risk of post-neonatal death was higher (OR 4.74, 95% CI 3.85-5.85; p < 0.01). CONCLUSIONS: Infant mortality in Down syndrome has an increasing trend. We postulate that these children are not accessing timely cardiac surgery, the main therapeutic tool to reduce the death risk in the first year of life.

TÍTULO / TITLE:    - Leisure Activity and Caregiver Involvement in Middle-Aged and Older Adults With Down Syndrome.

REVISTA / JOURNAL:    - Intellect Dev Disabil. 2017 Apr;55(2):97-109. doi: 10.1352/1934-9556-55.2.97.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1934-9556-55.2.97

AUTORES / AUTHORS: - Mihaila I; et al.

INSTITUCIÓN / INSTITUTION: - Iulia Mihaila and Sigan L. Hartley, University of Wisconsin - Madison.  

RESUMEN / SUMMARY: - The present study examined leisure activity and its association with caregiver involvement (i.e., residence and time spent with primary caregiver) in 62 middle-aged and older adults with Down syndrome (aged 30-53 years). Findings indicated that middle-aged and older adults with Down syndrome frequently participated in social and passive leisure activities, with low participation in physical and mentally stimulating leisure activities. Residence and time spent with primary caregiver were associated with participation in physical leisure activity. The findings suggest a need for support services aimed at increasing opportunities for participating in physical and mentally stimulating leisure activity by middle-aged and older adults with Down syndrome. These support services should partner with primary caregivers in order to best foster participation in physical leisure activity.

TÍTULO / TITLE:    - In search of quality indicators for Down syndrome healthcare: a scoping review.

REVISTA / JOURNAL:    - BMC Health Serv Res. 2017 Apr 18;17(1):284. doi: 10.1186/s12913-017-2228-x.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12913-017-2228-x

AUTORES / AUTHORS: - van den Driessen Mareeuw FA; et al.

INSTITUCIÓN / INSTITUTION: - Tranzo, Scientific Center for Care and Welfare, Faculty of Social and Behavioural Sciences, Tilburg University, PO Box 90153 (T-329), 5000 LE, Tilburg, The Netherlands.Department of Paediatrics, Jeroen Bosch Hospital, s-Hertogenbosch,  

RESUMEN / SUMMARY: - The medical care chain around Down syndrome (DS) is complex, with many multidisciplinary challenges. The current quality of care is unknown. Outcome-oriented quality indicators have the potential to improve medical practice and evaluate whether innovations are successful. This is particularly interesting for the evolving care for people with DS and intellectual disabilities (ID). The aim of this study was to identify existing indicators for medical DS care, by reviewing the literature. METHODS: We systematically searched six databases (PubMed, EMBASE, Web of Science, CINAHL, PsycINFO, Google Scholar) for studies concerning the development and implementation of quality indicators for DS and/or ID care, published until February 1st 2015. The scoping review method was used, including systematic data extraction and stakeholder consultation. RESULTS: We identified 13 studies concerning quality indicators for ID care that obtained data originating from questionnaires (patient/family/staff), medical files and/or national databases. We did not find any indicator sets specifically for DS care. Consulted stakeholders did not come up with additional indicator sets. Existing indicators for ID care predominantly focus on support services. Indicators in care for people with ID targeting medical care are scarce. Of the 70 indicators within the 13 indicator sets, 10% are structure indicators, 34% process, 32% outcome and 24% mixed. Ten of the 13 sets include indicators on the WHO quality dimensions ‘patient-centeredness’, ‘effectiveness’ and ‘efficiency’ of care. ‘Accessibility’ is covered by nine sets, ‘equitability’ by six, and ‘safety’ by four. Most studies developed indicators in a multidisciplinary manner in a joint effort with all relevant stakeholders; some used focus groups to include people with ID. CONCLUSION: To our knowledge, this is the first review that searched for studies on quality indicators in DS care. Hence, the study contributes to existing knowledge on DS care

RESPIRATORY - RESPIRATORIO

TÍTULO / TITLE:    - Urinary biomarkers and obstructive sleep apnea in patients with Down syndrome.

REVISTA / JOURNAL:    - Sleep Med. 2017 Jun;34:84-89. doi: 10.1016/j.sleep.2017.02.005. Epub 2017 Mar 7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.sleep.2017.02.005

AUTORES / AUTHORS: - Elsharkawi I; ... Skotko BG;

INSTITUCIÓN / INSTITUTION: - Down Syndrome Program, Division of Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.   bskotko@mgh.harvard.edu

RESUMEN / SUMMARY: - STUDY OBJECTIVES: The study aimed to compare urinary biomarkers in patients with Down syndrome (DS) with and without obstructive sleep apnea (OSA) to those of age- and sex-matched neurotypically developing healthy controls (HC). We further investigated whether we could predict OSA in patients with DS using these biomarkers. METHODS: Urine samples were collected from 58 patients with DS the night before or the morning after their scheduled overnight polysomnogram or both, of whom 47 could be age- and sex-matched to a sample of 43 HC. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay. Log-transformed creatinine-corrected assay levels were normalized. Normalized z-scores were compared between patients with DS vs. HC, between patients with DS with vs. without OSA, and to derive composite models to predict OSA. RESULTS: Most night-sampled urinary biomarkers were elevated among patients with DS relative to matched HC. No urinary biomarker levels differed between patients with DS with vs. without OSA. A combination of four urinary biomarkers predicted AHI> 1 with a positive predictive value of 90% and a negative predictive value of 68%. CONCLUSIONS: Having DS, even in the absence of concurrent OSA, is associated with a different urinary biomarker profile when compared to that of HC. Therefore, while urinary biomarkers may be predictive of OSA in the general pediatric population, a different approach is needed in interpreting urinary biomarker assays in patients with DS. Certain biomarkers also seem promising to be predictive of OSA in patients with DS. No clinical trial was indicated in the undertaking of this work.

TÍTULO / TITLE:    - Epidermal growth factor receptor-mutant lung cancer in Down syndrome: a case presentation and review of the literature.

REVISTA / JOURNAL:    - Oncotarget. 2017 Apr 25. doi: 10.18632/oncotarget.17406.

Enlace a la Editora de la Revista http://dx.doi.org/10.18632/oncotarget.17406

AUTORES / AUTHORS: - Li X; et al.

INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Xiaolan People’s Hospital Affiliated to Southern Medical University, Zhongshan, China.  

RESUMEN / SUMMARY: - Solid tumors have a markedly decreased incidence in individuals with Down syndrome (DS), including lung cancers. METHODS: The clinical presentation of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) in DS was reported and literature on the subject reviewed. RESULTS: In individuals with DS, the risk of lung cancer appears markedly lower. EGFR mutation and EGFR tyrosine kinase inhibitors (EGFR-TKIs) resistance also exist in DS with lung cancer. CONCLUSIONS: Clinicians should consider EGFR mutation and EGFR-TKIs resistance in lung cancer patients with DS

TÍTULO / TITLE:    - National cohort study showed that infants with Down’s syndrome faced a high risk of hospitalisation for the respiratory syncytial virus.

REVISTA / JOURNAL:    - Acta Paediatr. 2017 May 28. doi: 10.1111/apa.13937.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/apa.13937

AUTORES / AUTHORS: - Grut V; et al

INSTITUCIÓN / INSTITUTION: - Unit of Research, Education and Development, Ostersund Hospital, Ostersund, Sweden.  

RESUMEN / SUMMARY: - AIM: The respiratory syncytial virus (RSV) is a leading cause of hospitalisation in infants. We investigated this risk in children with Down’s syndrome under two years of age, adjusted for other known risk factors. METHODS: This national, retrospective 1:2 matched cohort study comprised all Swedish children born with Down’s from 2006-2011, who were each randomly matched to two controls without Down’s. Data on RSV hospitalisation and risk factors for RSV were obtained from national registers. The risk for RSV hospitalisation was assessed using multivariable Cox regression with pairwise stratification. RESULTS: The study comprised 814 children with Down’s and 1,628 controls. We found that 82 children with Down’s (10.1%) and 22 controls (1.4%) were hospitalised for RSV. The hazard ratio for children with Down’s was 4.00 (95% confidence interval 1.58-10.13) for up to one year of age and 6.60 (95% confidence interval 2.83-15.38) for up to two years of age, adjusted for other risk factors. During the second year of life, RSV hospitalisation continued for children with Down’s, while it was minimal for the controls. CONCLUSION: Children with Down’s faced a high risk of RSV hospitalisation, which continued beyond the first year of age. This article is protected by copyright. All rights reserved.

TÍTULO / TITLE:    - Isolated mild sleep-associated hypoventilation in children with Down syndrome.

REVISTA / JOURNAL:    - Arch Dis Child. 2017 Apr 13. pii: archdischild-2016-311694. doi: 10.1136/archdischild-2016-311694.

Enlace a la Editora de la Revista http://dx.doi.org/10.1136/archdischild-2016-311694

AUTORES / AUTHORS: - Wong W; Rosen D

INSTITUCIÓN / INSTITUTION: - Division of Respiratory Diseases, Boston Children’s Hospital, Boston, Massachusetts, USA   dennis.rosen@Childrens.harvard.edu

RESUMEN / SUMMARY: - Children with Down syndrome (DS) have a high incidence of obstructive sleep apnea (OSA) that is often associated with hypoventilation. Little is known, however, about the prevalence of sleep-associated hypoventilation independent of OSA in these children. METHODS: Retrospective chart review of all children with DS under 18 years of age undergoing polysomnography at a tertiary care paediatric hospital during a 2-year period. Exclusion criteria were as follow: those requiring oxygen or positive-pressure ventilation; with tracheostomy, baseline hypoxia, unrepaired cyanotic heart disease, pulmonary hypertension, and cerebral palsy; or OSA with >5 obstructions/hour. RESULTS: 86 children met inclusion criteria. 68 (79%) had ETCO2values >50 mm Hg during sleep. 37 (43%) ranged 50-55 mm Hg, and 12 (14%) met American Academy of Sleep Medicine criteria for hypoventilation of ETCO2 >50 mm Hg for >25% of total sleep time (TST). Average pulse-oximetry saturation (SpO2) values during sleep were 97.8% (SD +/-1; range: 95.1-99.9). Average percentage of TST with SpO2 >92% was 99.89%. CONCLUSION: Mildly elevated ETCO2 in the absence of OSA is common in children with DS. This may reflect underlying differences in autonomic control of ventilation in these children and may be considered a normal variant not necessitating intervention other than close monitoring for pulmonary hypertension.

TÍTULO / TITLE:    - Obstructive sleep apnea in Down syndrome: Benefits of surgery and noninvasive respiratory support.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 May 24. doi: 10.1002/ajmg.a.38283.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38283

AUTORES / AUTHORS: - Dudoignon B; et al

INSTITUCIÓN / INSTITUTION: - AP-HP, Hopital Necker-Enfants Malades, Pediatric Noninvasive Ventilation and Sleep Unit, Paris, France.  

RESUMEN / SUMMARY: - Children with Down syndrome are at increased risk of obstructive sleep apnea (OSA). The aim of the study was to describe the management of OSA in a large cohort of children with Down syndrome. A retrospective analysis of sleep studies and consequent management was performed for all consecutive Down syndrome patients evaluated between September 2013 and April 2016. The data of 57 patients were analyzed: 51/53 had an interpretable overnight polygraphy and 4 the recording of nocturnal gas exchange. Mean age at baseline sleep study was 6.2 +/- 5.9 years. Eighteen patients (32%) had prior upper airway surgery. Mean apnea-hypopnea index (AHI) was 14 +/- 16 events/hr with 41 of the 51 (80%) patients having OSA with an AHI> 1 event/hr and 20 patients (39%) having an AHI >/=10 events/hr. Consequently, eight patients (14%) had upper airway surgery. OSA improved in all patients except two who needed noninvasive respiratory support. Nineteen (33%) patients required noninvasive respiratory support. Mean age at noninvasive respiratory support initiation was 7 +/- 7 years. On 11 patients with objective adherence data available, mean compliance at 2 +/- 1 years of treatment was excellent with an average use per night of 8 hr46 +/- 3 hr59 and 9 patients using the noninvasive respiratory support >4 hr/night. Noninvasive respiratory support was associated with an improvement of nocturnal gas exchange. The prevalence of OSA is high in Down syndrome. Upper airway surgery is not always able to correct OSA. Noninvasive respiratory support represents then an effective treatment for OSA and good compliance may be achieved in a majority of patients.

TÍTULO / TITLE:    - The Efficacy of Adenotonsillectomy for Obstructive Sleep Apnea in Children with Down Syndrome: A Systematic Review.

REVISTA / JOURNAL:    - Otolaryngol Head Neck Surg. 2017 May 1:194599817703921. doi: 10.1177/0194599817703921.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0194599817703921

AUTORES / AUTHORS: - Nation J; Brigger M

INSTITUCIÓN / INSTITUTION: - 1 Otolaryngology/Head and Neck Surgery, Rady Children’s Hospital San Diego/University of California, San Diego, San Diego, California, USA.  

RESUMEN / SUMMARY: - Objective Determine the efficacy of adenotonsillectomy in children with Down syndrome. Data Sources Databases included PubMed, EMBASE, CINAHL, and Google Scholar. The search was inclusive of all references available through January 5, 2017. Review Methods A systematic review of the medical literature addressing adenotonsillectomy in treating obstructive sleep apnea in children with Down syndrome was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were pooled using a random-effects model where possible. The quality of studies was graded using the Methodological Index for Nonrandomized Studies criteria. Results Of the 957 articles screened, 5 met inclusion for the qualitative analysis and 3 met criteria for the quantitative analysis. The findings of the qualitative analysis were that adenotonsillectomy has a positive effect on children with Down syndrome but in many cases is noncurative, up to 75% need postoperative breathing support, there is a high rate of immediate postoperative airway needs, and there is no change in sleep efficiency or architecture. The articles consistently reported moderate success in improving polysomnographic parameters, and limited pooling of the data demonstrated a mean decrease of the apnea-hypopnea index by 51% (95% confidence interval [CI], 46%-55%). Conclusion A 51% reduction in the preoperative apnea-hypopnea index can be expected with the intervention of adenotonsillectomy alone in children with Down syndrome. This information is useful for counseling and managing patient and family expectations. It also serves as a reminder to clinicians to obtain a postoperative sleep study, as many of these patients will need nighttime airway support or secondary sleep surgery.

TÍTULO / TITLE:    - The effect of adenotonsillectomy on obstructive sleep apnea in children with Down syndrome.

REVISTA / JOURNAL:    - Acta Otolaryngol. 2017 Apr 11:1-8. doi: 10.1080/00016489.2017.1312016.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/00016489.2017.1312016

AUTORES / AUTHORS: - Abdel-Aziz M; et al

INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology, Faculty of Medicine , Cairo University , Cairo , Egypt.  

RESUMEN / SUMMARY: - OBJECTIVE: Children with Down syndrome (DS) are liable to develop obstructive sleep apnea (OSA) due to many anatomical airway abnormalities. The tonsils and adenoid occupy part of the airway space, and their removal may be helpful in relieving airway obstruction. The aim of this study was to assess the effectiveness of adenotonsillectomy in the treatment of OSA in those children. METHODS: Fifty DS children with difficult breathing were recruited, and they were subjected to polysomnographic examination (PSG). Patients with apnea-hypopnea index (AHI) > 1 were considered to have OSA. Adenotonsillectomy was performed for patients who had OSA and adenotonsillar hypertrophy, and after 3 months PSG was done for them with recording of the same preoperative parameters. RESULTS: Forty-three children demonstrated OSA on PSG, and they were included in the study. The preoperative mean AHI was 9.18 (+/- 6.17) that improved postoperatively to 2.72 (+/- 3.80) with its normalization in 72% of patients. Also, significant improvement of arousal index, minimum oxygen saturation, desaturation index, and peak end-tidal CO2 was achieved postoperatively. CONCLUSION: Adenotonsillectomy is an effective method for the treatment of OSA in children with DS. However, the condition may persist in some children who usually have airway narrowing at multiple levels.

TÍTULO / TITLE:    - A nationwide, cross-sectional survey on unusual sleep postures and sleep-disordered breathing-related symptoms in people with Down syndrome.

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2017 Apr 5. doi: 10.1111/jir.12379.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12379

AUTORES / AUTHORS: - Kuroda H; et al

INSTITUCIÓN / INSTITUTION: - Department of Health Sciences, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.  

RESUMEN / SUMMARY: - People with Down syndrome (DS) often have sleep-disordered breathing (SDB). Unusual sleep postures, such as leaning forward and sitting, are observed in people with DS. This study aimed to clarify the prevalence of unusual sleep postures and their relationships with SDB-related symptoms (SDB-RSs), such as snoring, witnessed apnoea, nocturnal awakening and excessive daytime sleepiness. METHODS: A questionnaire, including demographic characteristics and the presence of unusual sleep postures, as well as SDB-RSs, was completed by 1149 parents of people with DS from Japan. RESULTS: Unusual sleep postures were recorded in 483 (42.0%) people with DS. These participants were significantly younger and had a history of low muscle tone more frequently than people without unusual sleep postures. In all ages, the leaning forward posture was more frequent than sitting. People with DS with unusual sleep postures suffered from SDB-RSs. Those who slept in the sitting posture had more frequent SDB-RSs than did those who slept with the leaning forward posture. Snoring, witnessed apnoea and nocturnal awakening were observed in 73.6, 27.2 and 58.2% of participants, respectively. Snoring increased with aging. Witnessed apnoea was more common in males and in those with hypothyroidism than in females and in those without hypothyroidism. CONCLUSIONS: Our study shows that there is a close relationship between unusual sleep postures and SDB-RSs. We recommend that all people with DS with unusual sleep postures should be checked for the presence of SDB.

TÍTULO / TITLE:    - Urinary biomarkers and obstructive sleep apnea in patients with Down syndrome.

REVISTA / JOURNAL:    - Sleep Med. 2017 Jun;34:84-89. doi: 10.1016/j.sleep.2017.02.005. Epub 2017 Mar 7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.sleep.2017.02.005

AUTORES / AUTHORS: - Elsharkawi I; ... Skotko BG;

INSTITUCIÓN / INSTITUTION: - Down Syndrome Program, Division of Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.   bskotko@mgh.harvard.edu

RESUMEN / SUMMARY: - STUDY OBJECTIVES: The study aimed to compare urinary biomarkers in patients with Down syndrome (DS) with and without obstructive sleep apnea (OSA) to those of age- and sex-matched neurotypically developing healthy controls (HC). We further investigated whether we could predict OSA in patients with DS using these biomarkers. METHODS: Urine samples were collected from 58 patients with DS the night before or the morning after their scheduled overnight polysomnogram or both, of whom 47 could be age- and sex-matched to a sample of 43 HC. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay. Log-transformed creatinine-corrected assay levels were normalized. Normalized z-scores were compared between patients with DS vs. HC, between patients with DS with vs. without OSA, and to derive composite models to predict OSA. RESULTS: Most night-sampled urinary biomarkers were elevated among patients with DS relative to matched HC. No urinary biomarker levels differed between patients with DS with vs. without OSA. A combination of four urinary biomarkers predicted AHI> 1 with a positive predictive value of 90% and a negative predictive value of 68%. CONCLUSIONS: Having DS, even in the absence of concurrent OSA, is associated with a different urinary biomarker profile when compared to that of HC. Therefore, while urinary biomarkers may be predictive of OSA in the general pediatric population, a different approach is needed in interpreting urinary biomarker assays in patients with DS. Certain biomarkers also seem promising to be predictive of OSA in patients with DS. No clinical trial was indicated in the undertaking of this work.

THERAPEUTICS - TERAPÉUTICA

TÍTULO / TITLE:    - Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

REVISTA / JOURNAL:    - Physiol Behav. 2017 Aug 1;177:230-241. doi: 10.1016/j.physbeh.2017.05.003. Epub 2017 May 3.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.physbeh.2017.05.003

AUTORES / AUTHORS: - Stringer M; ... Roper RJ;

INSTITUCIÓN / INSTITUTION: - IUPUI, Department of Biology, 723 West Michigan Street, SL 306, Indianapolis, IN 46202-3275, United States.   rjroper@iupui.edu

RESUMEN / SUMMARY: - Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis in

TÍTULO / TITLE:    - Parental Perspectives on Pharmacological Clinical Trials: a Qualitative Study in Down Syndrome and Fragile X Syndrome.

REVISTA / JOURNAL:    - J Genet Couns. 2017 May 24. doi: 10.1007/s10897-017-0111-x.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10897-017-0111-x

AUTORES / AUTHORS: - Reines V; ... Visootsak J;

INSTITUCIÓN / INSTITUTION: - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Ovid Therapeutics, 1460 Broadway, New York, NY, 10036, USA.   jvisootsak@ovidrx.com

RESUMEN / SUMMARY: - Research studies focusing on parents’ perspectives of pharmacological clinical trials have not kept pace with the number of emerging pharmacologic clinical trials in Down syndrome (DS) and Fragile X syndrome (FXS). Since individuals with DS or FXS have limited cognitive ability to make decisions about their participation in clinical trials, it is important to consider the parents’ perspectives and explore the ways in which decisions are made for their children. Using a semi-structured interview, we enrolled 9 parents of a child(ren) with FXS and 15 with a child with DS to analyze their views, experiences, and knowledge of pharmacological clinical trials. Although our study is preliminary in nature, it revealed that parents are generally supportive of pharmacological clinical trials, yet there may be concerns about safety and long-term implications and consideration for their child in the decision process. There is also parental misunderstanding of the objectives of pharmacological clinical trials; thus, it is important for pharmaceutical companies, study investigators, clinicians/medical professionals, and parent advocacy groups to collaborate to provide appropriate and up-to-date educational resources that fully explain the risks and benefits of clinical trials.

TÍTULO / TITLE:    - Outcome Measures for Clinical Trials in Down Syndrome.

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 May;122(3):247-281. doi: 10.1352/1944-7558-122.3.247.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.3.247

AUTORES / AUTHORS: - Esbensen AJ;

INSTITUCIÓN / INSTITUTION: - Cincinnati Children’s Hospital Medical Center;  

RESUMEN / SUMMARY: - Increasingly individuals with intellectual and developmental disabilities, including Down syndrome, are being targeted for clinical trials. However, a challenge exists in effectively evaluating the outcomes of these new pharmacological interventions. Few empirically evaluated, psychometrically sound outcome measures appropriate for use in clinical trials with individuals with Down syndrome have been identified. To address this challenge, the National Institutes of Health (NIH) assembled leading clinicians and scientists to review existing measures and identify those that currently are appropriate for trials; those that may be appropriate after expansion of age range addition of easier items, and/or downward extension of psychometric norms; and areas where new measures need to be developed. This article focuses on measures in the areas of cognition and behavior.

TÍTULO / TITLE:    - Pharmacokinetic Properties of Memantine Following a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down’s Syndrome.

REVISTA / JOURNAL:    - Basic Clin Pharmacol Toxicol. 2017 May 30. doi: 10.1111/bcpt.12816.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/bcpt.12816

AUTORES / AUTHORS: - Victorino DB; et al.

INSTITUCIÓN / INSTITUTION: - Division of Neurology and Epilepsy, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.  

RESUMEN / SUMMARY: - Memantine is a drug approved for the treatment of moderate-to-severe Alzheimer’s disease (AD), and there is ongoing research on the potential expansion of its clinical applicability. Published data on the pharmacokinetics of memantine in the mouse is still incomplete, particularly for chronic administration regimens and mouse models of specific genetic disorders. Down’s syndrome (DS) is a genetic disorder known to affect multiple organs and systems, with the potential to alter significantly drug pharmacokinetics. Here, we describe a simple, efficient and sensitive GC/MS-based procedure for the determination of memantine concentrations in murine blood and tissue samples. We analysed pharmacokinetic properties of memantine, particularly its distribution in blood, brain and liver in the Ts65Dn mouse model of DS and euploid F1 hybrid mice after single intraperitoneal administrations of increasing doses of this drug. We also determined steady-state memantine concentrations in plasma, brain and liver following chronic oral administration of this drug in adult male Ts65Dn mice, euploid littermate controls and nursing or pregnant Ts65Dn mice. Our results revalidated the acute dose of memantine used in previously published work, determined the appropriate amount of memantine to be mixed into mouse chow to achieve steady and pharmacologically relevant plasma and tissue levels of this drug, and demonstrated that memantine can be transferred from mother to offspring via maternal milk and placenta. Most of these findings are potentially applicable not only to the study of DS but also to other neurodevelopmental and neurodegenerative disorders.

TÍTULO / TITLE:    - Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome.

REVISTA / JOURNAL:    - Sci Rep. 2017 Apr 3;7:45561. doi: 10.1038/srep45561.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/srep45561

AUTORES / AUTHORS: - Kazim SF; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurochemistry, and SUNY Downstate/NYSIBR Center for Developmental Neuroscience, New York State Institute for Basic Research (NYSIBR), Staten Island, NY 10314, USA.; The Robert F. Furchgott Center for Neural and Behavioral  

RESUMEN / SUMMARY: - Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3beta) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model.

EDUCATION - EDUCACIÓN

TÍTULO / TITLE:    - Counting Ability in Down Syndrome: The Comprehension of the One-to-One Correspondence Principle and the Role of Receptive Vocabulary.

REVISTA / JOURNAL:    - Neuropsychology. 2017 Apr 13. doi: 10.1037/neu0000377.

Enlace a la Editora de la Revista http://dx.doi.org/10.1037/neu0000377

AUTORES / AUTHORS: - Abreu-Mendoza RA; Arias-Trejo N

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - The authors investigated whether children with Down’s syndrome (DS) who have not started to produce number words understand the one-to-one correspondence principle (Experiment 1), and they looked at the relationship between number word knowledge and receptive vocabulary (Experiment 2). METHOD: Sixteen children with DS who did not recite the count list participated in Experiment 1, along with 2 comparison groups: 1 of 16 children with DS who recited up to 10, paired by chronological age, and another of 16 typically developing children paired by their ability to recite the list. The understanding of the principle was evaluated by a preferential looking task. Children saw 1 of 2 conditions. In the number condition, they heard number words and in the beep condition they heard computerized beeps. In both conditions, children saw videos depicting counting events that were principle-consistent or principle-inconsistent. Experiment 2 evaluated 25 children with DS using the Give-a-Number task and the Receptive Vocabulary subtest of the Wechsler Preschool and Primary Scale of Intelligence-III. RESULTS: In Experiment 1, children in the number condition preferred principle-consistent videos, independent of their ability to recite the count list. Experiment 2 showed a strong correlation between number word knowledge and receptive vocabulary scores, independent of chronological age. CONCLUSIONS: The results suggest that the difficulty of children with DS in acquiring counting ability might not reflect a lack of understanding of the one-to-one correspondence principle, but might instead be related to vocabulary development. (PsycINFO Database Record

TÍTULO / TITLE:    - The effectiveness of the computerized visual perceptual training program on individuals with Down syndrome: An fMRI study.

REVISTA / JOURNAL:    - Res Dev Disabil. 2017 May 20;66:1-15. doi: 10.1016/j.ridd.2017.04.015.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2017.04.015

AUTORES / AUTHORS: - Wan YT;... Wuang YP

INSTITUCIÓN / INSTITUTION: - Department of Occupational Therapy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.   yeepwu@cc.kmu.edu.tw

RESUMEN / SUMMARY: - This study investigated the effectiveness of the Computerized Visual Perception Training (CVPT) program on individuals with Down syndrome (DS, mean age=13.17+/-4.35years, age range: 6.54-20.75 years). All participants have mild intellectual disability classified by the standard IQ measures (mean=61.2, ranges from 55 to 68). Both the Test of Visual Perceptual Skill- Third Edition (TVPS-3) and functional magnetic resonance imaging (fMRI) were used to evaluate the training outcomes. Results of TVPS-3 and fMRI showed that DS group had visual perceptual deficits and abnormal neural networks related to visual organization. The results showed that DS intervention group had significant improvements on TVPS-3 after intervention. The fMRI results indicated more activation in superior and inferior parietal lobes (spatial manipulation), as well as precentral gyrus and dorsal premotor cortex (motor imagery) in DS intervention group. The CVPT program was effective in improving visual perceptual functions and enhancing associated cortical activations in DS.

TÍTULO / TITLE:    - Training spatial-simultaneous working memory in individuals with Down syndrome.

REVISTA / JOURNAL:    - Res Dev Disabil. 2017 Apr 4;64:118. doi: 10.1016/j.ridd.2017.03.012.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2017.03.012

AUTORES / AUTHORS: - Lanfranchi S; et al

INSTITUCIÓN / INSTITUTION: - Department of Developmental Psychology and Socialization, University of Padova, Italy.   silvia.lanfranchi@unipd.it

RESUMEN / SUMMARY: - Recent studies have suggested that the spatial-simultaneous component of working memory (WM), which is involved when stimuli are presented simultaneously, is selectively impaired in individuals with Down syndrome (DS). The main objective of the present study was to examine whether WM performance can be enhanced in individuals with DS by analyzing the immediate and maintenance effects of a training program. For this purpose, 61 individuals with DS were randomly assigned to three groups: one trained on simultaneous components of visuospatial WM; one serving as an active control group, that completed activities on vocabulary; and one serving as a passive control group, that only attended the pre- and post-test and follow-up assessments. The efficacy of the training was analyzed in terms of specific (spatial-simultaneous WM tasks), near transfer (spatial-sequential and verbal WM tasks), far transfer (spatial abilities, everyday competences), and maintenance effects (with a follow-up at 1 month). The results showed an overall significant effect on the WM on the group receiving the training. The benefit was generally specific, however, with some transfer to other WM tasks, but only in the immediate (post-test) assessment.

TÍTULO / TITLE:    - POSEIDON - Bringing Assistive Technology to People with Down Syndrome: Results of a Three Year European Project.

REVISTA / JOURNAL:    - Stud Health Technol Inform. 2017;236:169-175.

AUTORES / AUTHORS: - Engler A; Schulze E

INSTITUCIÓN / INSTITUTION: - Berlin Institute for Social Research, Germany.  

RESUMEN / SUMMARY: - The POSEIDON project aimed to increase the independence and autonomy of people with Down syndrome with the help of technical assistants. It followed a user-centered approach by involving people with Down syndrome and their parents, carers etc. A requirement analysis was the first step of the project. It became clear that people with Down syndrome especially need support in the areas of time management, mobility and money handling. Different applications were developed which were tested and evaluated in two field tests in three countries. Results indicate that POSEIDON can help to overcome daily challenges and that it can increase the autonomy and independence of people with Down syndrome.

TÍTULO / TITLE:    - Associations of Child and Adolescent Mastery Motivation and Self-Regulation With Adult Outcomes: A Longitudinal Study of Individuals With Down Syndrome.

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 May;122(3):235-246. doi: 10.1352/1944-7558-122.3.235.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.3.235

AUTORES / AUTHORS: - Gilmore L; Cuskelly M.

INSTITUCIÓN / INSTITUTION: - Queensland University of Technology; and Monica Cuskelly, The University of Tasmania.  

RESUMEN / SUMMARY: - This 20-year prospective longitudinal study focuses on the contribution of mastery motivation and self-regulation to adult outcomes for individuals with Down syndrome. In earlier phases of the research, 25 participants completed measures of cognitive ability, mastery motivation and self-regulation in childhood (4 to 6 years) and adolescence (11 to 15 years). In the adult phase reported here, self-determination and adaptive behavior were assessed in 21 of the original participants at age 23 to 26 years. Mastery motivation and self-regulation made unique contributions to adult outcomes, over and above the effects of cognitive ability. The findings provide powerful evidence about the important role of child and adolescent mastery motivation and self-regulation for the adult lives of individuals with Down syndrome.

TÍTULO / TITLE:    - Vocalization patterns in young children with Down syndrome: Utilizing the language environment analysis (LENA) to inform behavioral phenotypes.

REVISTA / JOURNAL:    - J Intellect Disabil. 2017 Jan 1:1744629517708091. doi: 10.1177/1744629517708091.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/1744629517708091

AUTORES / AUTHORS: - Parikh C; Mastergeorge AM;

INSTITUCIÓN / INSTITUTION: - Texas Tech University, USA.  

RESUMEN / SUMMARY: - Children with Down syndrome (DS) are at higher risk for both delayed expressive language and poor speech intelligibility. The current study utilized the quantitative automated language environment analysis (LENA) to depict mother and child vocalizations and conversational patterns in the home of 43 children with DS, chronologically aged 24-64 months. Children with DS displayed fewer utterances than typically developing children; however, there was wide variability. Furthermore, children with DS did not show increased vocalization counts across their chronological ages. In contrast to previous findings, this study found that the mothers of children with DS had a reduced number of vocalizations. However, the vocalizations increased with age in comparison to mothers of typically developing children. Implications for targeted interventions that facilitate learning opportunities in bidirectional contexts for children with DS and their parents are discussed, with particular attention to quantify behavioral phenotypes utilizing a novel expressive language assessment tool.

TÍTULO / TITLE:    - Core vocabulary of young children with Down syndrome.

REVISTA / JOURNAL:    - Augment Altern Commun. 2017 Jun;33(2):77-86. doi: 10.1080/07434618.2017.1293730. Epub 2017 Mar 2.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/07434618.2017.1293730

AUTORES / AUTHORS: - Deckers SRJM; et al

INSTITUCIÓN / INSTITUTION: - a Center of Expertise Interprofessional Collaboration, Fontys University of Applied Sciences , Eindhoven , the Netherlands.  

RESUMEN / SUMMARY: - The aim of this study was to develop a core vocabulary list for young children with intellectual disabilities between 2 and 7 years of age because data from this population are lacking in core vocabulary literature. Children with Down syndrome are considered one of the most valid reference groups for researching developmental patterns in children with intellectual disabilities; therefore, spontaneous language samples of 30 Dutch children with Down syndrome were collected during three different activities with multiple communication partners (free play with parents, lunch- or snack-time at home or at school, and speech therapy sessions). Of these children, 19 used multimodal communication, primarily manual signs and speech. Functional word use in both modalities was transcribed. The 50 most frequently used core words accounted for 67.2% of total word use; 16 words comprised core vocabulary, based on commonality. These data are consistent with similar studies related to the core vocabularies of preschoolers and toddlers with typical development, although the number of nouns present on the core vocabulary list was higher for the children in the present study. This finding can be explained by manual sign use of the children with Down syndrome and is reflective of their expressive vocabulary ages.

TÍTULO / TITLE:    - The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and Practice Effects.

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 May;122(3):215-234. doi: 10.1352/1944-7558-122.3.215.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.3.215

AUTORES / AUTHORS: - Edgin JO;et al.

INSTITUCIÓN / INSTITUTION: - Jamie O. Edgin and Payal Anand, University of Arizona;  

RESUMEN / SUMMARY: - A multisite study investigated the test-retest reliability and practice effects of a battery of assessments to measure neurocognitive function in individuals with Down syndrome (DS). The study aimed to establish the appropriateness of these measures as potential endpoints for clinical trials. Neurocognitive tasks and parent report measures comprising the Arizona Cognitive Test Battery (ACTB) were administered to 54 young participants with DS (7-20 years of age) with mild to moderate levels of intellectual disability in an initial baseline evaluation and a follow-up assessment 3 months later. Although revisions to ACTB measures are indicated, results demonstrate adequate levels of reliability and resistance to practice effects for some measures. The ACTB offers viable options for repeated testing of memory, motor planning, behavioral regulation, and attention. Alternative measures of executive functioning are required.
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