CITAS BIBLIOGRÁFICAS
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Septiembre 2017 - Octubre 2017
September 2017 - October 2017


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AGING - ENVEJECIMIENTO

TÍTULO / TITLE:    - Clinical aspects and biomarkers of Alzheimer’s disease in Down syndrome.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Sep 1. pii: S0891-5849(17)30740-2. doi: 10.1016/j.freeradbiomed.2017.08.02

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.024

AUTORES / AUTHORS: - Zis P; Strydom A

INSTITUCIÓN / INSTITUTION: - Division of Psychiatry, University College London, London, UK; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neurosciences, King’s College London, London, UK; The LonDownS Consortium, London   andre.strydom@kcl.ac.uk

RESUMEN / SUMMARY: - Alzheimer’s disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21, with neuropathology that is comparable to Sporadic AD and Familial AD (FAD). Previous literature suggested some unique features in clinical presentation of dementia in DS (DSd), which might be due to diagnostic difficulties, or represent a real difference compared to SAD or FAD. We review current knowledge on clinical diagnosis and presentation of dementia in DS in comparison with FAD due to APP mutations and APP duplication. We suggest that the clinical presentation in DS (prominent memory decline and behavioral symptoms, and early development of myoclonus and seizures) are similar to the clinical features associated with APP mutations that is known to have an increased Abeta42/ Abeta40 ratio, and highlight the relative lack of vascular complications associated with cerebral amyloid angiopathy in DS in comparison with those rare individuals with FAD due to duplication APP. We consider the biomarker evidence associated with DS and DSd with reference to Abeta peptide levels and oxidative stress, and suggest future directions for research to explore the potential mechanisms associated with the clinical presentation of DSd.

TÍTULO / TITLE:    - Exosomal biomarkers in Down syndrome and Alzheimer’s disease.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Sep 5. pii: S0891-5849(17)30744-X. doi: 10.1016/j.freeradbiomed.2017.08.02

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.028

AUTORES / AUTHORS: - Hamlett ED; et al. Granholm AC;

INSTITUCIÓN / INSTITUTION: - Knoebel Institute for Healthy Aging and the Department of Biological Sciences, University of Denver, Denver, CO, USA; Medical University of South Carolina, Charleston, SC, USA.   Bentley@DU.edu

RESUMEN / SUMMARY: - Every person with Down syndrome (DS) has the characteristic features of Alzheimer’s disease (AD) neuropathology in their brain by the age of forty, and most go on to develop AD dementia. Since people with DS show highly variable levels of baseline function, it is often difficult to identify early signs of dementia in this population. The discovery of blood biomarkers predictive of dementia onset and/or progression in DS is critical for developing effective clinical diagnostics. Our recent studies show that neuron-derived exosomes, which are small extracellular vesicles secreted by most cells in the body, contain elevated levels of amyloid-beta peptides and phosphorylated-Tau that could indicate a preclinical AD phase in people with DS starting in childhood. We also found that the relative levels of these biomarkers were altered following dementia onset. Exosome release and signaling are dependent on cellular redox homeostasis as well as on inflammatory processes, and exosomes may be involved in the immune response, suggesting a dual role as both triggers of inflammation in the brain and propagators of inflammatory signals between brain regions. Based on recently reported connections between inflammatory processes and exosome release, the elevated neuroinflammatory state observed in people with DS may affect exosomal AD biomarkers. Herein, we discuss findings from studies of people with DS, people with DS and AD (DS-AD), and mouse models of DS showing new connections between neuroinflammatory pathways, oxidative stress, exosomes, and exosome-mediated signaling, which may inform future AD diagnostics, preventions, and treatments in the DS population as well as in the general population.

TÍTULO / TITLE:    - mTOR in Down syndrome: Role in Ass and tau neuropathology and transition to Alzheimer disease-like dementia.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Aug 12. pii: S0891-5849(17)30725-6. doi:

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.009

AUTORES / AUTHORS: - Di Domenico F; et al. Butterfield DA;

INSTITUCIÓN / INSTITUTION: - Department of Chemistry and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506 USA.   dabcns@uky.edu

RESUMEN / SUMMARY: - The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase involved in the regulation of protein synthesis and degradation, longevity and cytoskeletal formation. The mTOR pathway represents a key growth and survival pathway involved in several diseases such as cancer, obesity, cardiovascular disease and neurodegenerative diseases. Numerous studies linked the alterations of mTOR pathway to age-dependent cognitive decline, pathogenesis of Alzheimer disease (AD) and AD-like dementia in Down syndrome (DS). DS is the most frequent chromosomal abnormality that causes intellectual disability. The neuropathology of AD in DS is complex and involves impaired mitochondrial function, defects in neurogenesis, increased oxidative stress, altered proteostasis and autophagy networks as a result of triplication of chromosome 21(chr 21). The chr21 gene products are considered a principal neuropathogenic moiety in DS. Several genes involved respectively in the formation of senile plaques and neurofibrillary tangles (NFT), two main pathological hallmarks of AD, are mapped on chr21. Further, in subjects with DS the activation of mTOR signaling contributes to Abeta generation and the formation of NFT. This review discusses recent research highlighting the complex role of mTOR associated with the presence of two hallmarks of AD pathology, senile plaques (composed mostly of fibrillar Ass peptides), and NFT (composed mostly of hyperphosphorylated tau protein). Oxidative stress, associated with chr21-related Abeta and mitochondrial alterations, may significantly contribute to this linkage of mTOR to AD-like neuropathology in DS.

TÍTULO / TITLE:    - Family members and health professionals’ perspectives on future life planning of ageing people with Down syndrome: a qualitative study.

REVISTA / JOURNAL:    - Disabil Rehabil. 2017 Aug 8:1-8. doi: 10.1080/09638288.2017.1362595.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/09638288.2017.1362595

AUTORES / AUTHORS: - Covelli V; Leonardi M; et al

INSTITUCIÓN / INSTITUTION: - b Neurology, Public Health and Disability Unit - Scientific Directorate , Neurological Institute C. Besta IRCCS Foundation , Milan , Italy.  

RESUMEN / SUMMARY: - To address the way in which primary caregivers of people over 45 with Down syndrome describe daily life activities and context and foresee their future. METHODS: Thirteen family members and 15 health professionals participated to four focus groups. Meaningful concepts were identified and linked to the International Classification of Functioning, Disability and Health using established linking rules. RESULTS: A total of 258 relevant concepts were identified and linked to 75 categories of the classification: 38 were from activity and participation and 17 from environmental factors domains. The most commonly reported issues were mental functions (b117-intellectual functions and b152-emotional functions), community life activities (d910-community life and d920-recreation and leisure) and environmental factors (e310-support of immediate family, e355-support from health professionals and e555-associations and organizational services). CONCLUSIONS: Information on the daily life and health of ageing people with Down syndrome is important to plan social and health care interventions tailored to deal with problems that they may encounter in older age. Considering the interaction between health and environment and maintaining a continuity of daily routines were reported as the most relevant topics for managing daily lives of persons with Down syndrome in older ages. Implications for rehabilitation Pay more attention to the interaction between environmental factors and health condition in ageing people with Down syndrome. Information about the life contest are important in order to plan present and future social-health care interventions. Future planning for people with Down syndrome is a great concern for family members.

TÍTULO / TITLE:    - PET Imaging of Tau Pathology and Relationship to Amyloid, Longitudinal MRI, and Cognitive Change in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI).

REVISTA / JOURNAL:    - J Alzheimers Dis. 2017;60(2):439-450. doi: 10.3233/JAD-170390.

Enlace a la Editora de la Revista http://dx.doi.org/10.3233/JAD-170390

AUTORES / AUTHORS: - Rafii MS; et al.

INSTITUCIÓN / INSTITUTION: - Alzheimer’s Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, San Diego, USA. Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA, USA..  

RESUMEN / SUMMARY: - BACKGROUND: Adults with Down syndrome (DS) represent an enriched population for the development of Alzheimer’s disease (AD), which could aid the study of therapeutic interventions, and in turn, could benefit from discoveries made in other AD populations. OBJECTIVES: 1) Understand the relationship between tau pathology and age, amyloid deposition, neurodegeneration (MRI and FDG PET), and cognitive and functional performance; 2) detect and differentiate AD-specific changes from DS-specific brain changes in longitudinal MRI. METHODS: Twelve non-demented adults, ages 30 to 60, with DS were enrolled in the Down Syndrome Biomarker Initiative (DSBI), a 3-year, observational, cohort study to demonstrate the feasibility of conducting AD intervention/prevention trials in adults with DS. We collected imaging data with 18F-AV-1451 tau PET, AV-45 amyloid PET, FDG PET, and volumetric MRI, as well as cognitive and functional measures and additional laboratory measures. RESULTS: All amyloid negative subjects imaged were tau-negative. Among the amyloid positive subjects, three had tau in regions associated with Braak stage VI, two at stage V, and one at stage II. Amyloid and tau burden correlated with age. The MRI analysis produced two distinct volumetric patterns. The first differentiated DS from normal (NL) and AD, did not correlate with age or amyloid, and was longitudinally stable. The second pattern reflected AD-like atrophy and differentiated NL from AD. Tau PET and MRI atrophy correlated with several cognitive and functional measures. CONCLUSIONS: Tau accumulation is associated with amyloid positivity and age, as well as with progressive neurodegeneration measurable using FDG and MRI. Tau correlates with cognitive decline, as do AD-specific hypometabolism and atrophy.

TÍTULO / TITLE:    - Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome.

REVISTA / JOURNAL:    - Mol Neurodegener. 2017 Sep 4;12(1):63. doi: 10.1186/s13024-017-0206-8.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13024-017-0206-8

AUTORES / AUTHORS: - Tatebe H; Tokuda T; et al

INSTITUCIÓN / INSTITUTION: - Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan.   ttokuda@koto.kpu-m.ac.jp

RESUMEN / SUMMARY: - BACKGROUND: There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer’s disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD. METHODS: We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts. RESULTS: In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0.171 +/- 0.166 pg/ml in AD versus 0.0405 +/- 0.0756 pg/ml in controls, p = 0.0039). The percentage of the subjects whose levels of plasma p-tau181 exceeded the cut-off value (0.0921 pg/ml) was significantly higher in the AD group compared with the control group (60% in AD versus 16.7% in controls, p = 0.0090). In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age-matched controls, the plasma concentrations of p-tau181 were significantly higher in the DS group (0.767 +/- 1.26 pg/ml in DS versus 0.0415 +/- 0.0710 pg/ml in controls, p = 0.0313). There was a significant correlation between the plasma levels of p-tau181 and age in the DS group (R2 = 0.4451, p = 0.0013). All of the DS individuals showing an extremely high concentration of plasma p-tau181 (> 1.0 pg/ml) were older than the age of 40. In the third cohort composed of 8 AD patients and 3 patients with other neurological diseases, the levels of plasma p-tau181 significantly correlated with those of CSF p-tau181 (R2 = 0.4525, p = 0.023). CONCLUSIONS: We report for the first time quantitative data on the plasma levels of p-tau181 in controls and patients with AD and DS, and these data suggest that the plasma p-tau181 is a promising blood biomarker for brain AD pathology. This exploratory pilot study warrants further large-scale and well-controlled

TÍTULO / TITLE:    - Longitudinal telomere shortening and early Alzheimer’s disease progression in adults with down syndrome.

REVISTA / JOURNAL:    - Am J Med Genet B Neuropsychiatr Genet. 2017 Aug 30. doi: 10.1002/ajmg.b.32575.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.b.32575

AUTORES / AUTHORS: - Jenkins EC; Silverman WP; et al.

INSTITUCIÓN / INSTITUTION: - The Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, Maryland.  

RESUMEN / SUMMARY: - Telomere shortening was shown to parallel Alzheimer’s disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T-lymphocyte interphases from individuals with Down syndrome (DS) with and without “mild cognitive impairment” (MCI-DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI-DS in this high-risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (N = 4 Female, N = 6 Male) developing MCI-DS. Cases were selected blind to telomere length from a sample of adults with DS previously enrolled in a prospective longitudinal study at 18-month intervals with clinical and telomere assessments: (1) MCI-DS group data were collected approximately three years prior to development of MCI-DS; (2) 18 months later; (3) when MCI-DS was first observed. These telomere measures were compared to those from another 10 adults with DS matched by sex and approximate age but without indications of MCI-DS (Controls). PNA (peptide nucleic acid) probes for telomeres together with a chromosome two centromere probe were used. Findings indicated telomere shortening over time for both Cases and Controls. Group differences emerged by 18-months prior to recognition of MCI-DS onset and completely non-overlapping distributions of telomere measures were observed by the time of MCI-DS onset. This study adds to accumulating evidence of the value of telomere length, as an early biomarker of AD progression in adults with Down syndrome.

TÍTULO / TITLE:    - Lifestyle factors and Alzheimer’s disease in people with Down syndrome.

REVISTA / JOURNAL:    - Livewell Southwest CIC, Plymouth, UK.

Enlace a la Editora de la Revista J Appl Res Intellect Disabil. 2017 Jul 30. doi: 10.1111/jar.12369.

AUTORES / AUTHORS: - http://dx.doi.org/10.1111/jar.12369

INSTITUCIÓN / INSTITUTION: - Livewell Southwest CIC, Plymouth, UK.  

RESUMEN / SUMMARY: - Lifestyle has previously been associated with the onset of Alzheimer’s disease (AD) in the typically developing population, but research investigating this association in Down syndrome (DS) is limited. METHOD: Adults with DS and AD (n = 27) were compared to adults with DS without AD (n = 30) on physical activity, diet, weight, where participants currently lived, where participants had lived for the majority of their lives, educational attainment, occupational attainment and cognitive activity. RESULTS: There was a significant difference between samples on where participants currently lived, with the majority of the clinical sample living in institutionalized settings and the majority of the control sample living in independent/supported living settings. This may reflect a tendency to move people once they start to deteriorate which, if correct, is contrary to clinical recommendations that people with AD should be supported to “die in place.” CONCLUSIONS: Further research into the way in which lifestyle factors, particularly living environment, could contribute to the increased risk of AD in adults with DS is required. This may support interventions aimed at preventing or delaying the onset of the disease.

TÍTULO / TITLE:    - Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities.

REVISTA / JOURNAL:    - Acta Neuropathol Commun. 2017 Aug 29;5(1):65. doi: 10.1186/s40478-017-0466-0.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s40478-017-0466-0

AUTORES / AUTHORS: - Gauthier SA; et al

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

RESUMEN / SUMMARY: - A dysfunctional endosomal pathway and abnormally enlarged early endosomes in neurons are an early characteristic of Down syndrome (DS) and Alzheimer’s disease (AD). We have hypothesized that endosomal material can be released by endosomal multivesicular bodies (MVBs) into the extracellular space via exosomes to relieve neurons of accumulated endosomal contents when endosomal pathway function is compromised. Supporting this, we found that exosome secretion is enhanced in the brains of DS patients and a mouse model of the disease, and by DS fibroblasts. Furthermore, increased levels of the tetraspanin CD63, a regulator of exosome biogenesis, were observed in DS brains. Importantly, CD63 knockdown diminished exosome release and worsened endosomal pathology in DS fibroblasts. Taken together, these data suggest that increased CD63 expression enhances exosome release as an endogenous mechanism mitigating endosomal abnormalities in DS. Thus, the upregulation of exosome release represents a potential therapeutic goal for neurodegenerative disorders with endosomal pathology.

TÍTULO / TITLE:    - Epidemiology of estrogen and dementia in women with Down syndrome.

REVISTA / JOURNAL:    - ree Radic Biol Med. 2017 Aug 31. pii: S0891-5849(17)30735-9. doi: 10.1016/j.freeradbiomed.2017.08.01

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.019

AUTORES / AUTHORS: - Schupf N; et al

INSTITUCIÓN / INSTITUTION: - Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United States; G.H. Sergievsky Center, Columbia University, New York, NY, United States; Departments of Neurology and Psychiatry, Col   ns24@cumc.columbia.edu

RESUMEN / SUMMARY: - Several lines of investigation have shown a protective role for estrogen in Alzheimer’s disease through a number of biological actions. This review examines studies of the role of estrogen-related factors in age at onset and risk for Alzheimer’s disease in women with Down syndrome, a population at high risk for early onset of dementia. The studies are consistent in showing that early age at menopause and that low levels of endogenous bioavailable estradiol in postmenopausal women with Down syndrome are associated with earlier age at onset and overall risk for dementia. Polymorphisms in genes associated with estrogen receptor activity and in genes for estrogen biosynthesis affecting endogenous estrogen are related to age at onset and cumulative incidence of dementia, and may serve as biomarkers of risk. To date, no clinical trials of estrogen or hormone replacement therapy (ERT/HRT) have been published for women with Down syndrome. While findings from clinical trials of ERT or HRT for dementia have generally been negative among women in the neurotypical population, the short interval between menopause and onset of cognitive decline, together with a more positive balance between potential benefits and risks, suggests an opportunity to evaluate the efficacy of ERT/HRT for delaying or preventing dementia in this high risk population, although questions concerning the optimal formulation and timing of the hormone therapy are not yet resolved.

TÍTULO / TITLE:    - Down syndrome, beta-amyloid and neuroimaging.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Sep 19. pii: S0891-5849(17)30756-6. doi: 10.1016/j.freeradbiomed.2017.09.0

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.09.013

AUTORES / AUTHORS: - Head E; et al

INSTITUCIÓN / INSTITUTION: - University of Kentucky, Sanders-Brown Center on Aging, 800 South Limestone Street, Lexington, KY 40536, United States; University of Kentucky, Department of Pharmacology & Nutritional Sciences, Lexington, KY 40536, United States.   elizabeth.head@uky.edu

RESUMEN / SUMMARY: - This review focuses on the role of Abeta in AD pathogenesis in Down syndrome and current approaches for imaging Abeta in vivo. We will describe how Abeta deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Abeta includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Abeta have been published and are summarized here. In combination, we have learned a great deal about Abeta in DS in terms of characterizing age of onset of this pathology and it is exciting to note that there is a clinical trial in DS targeting Abeta that may lead to clinical benefits.

CARDIOLOGY - CARDIOLOGÍA

TÍTULO / TITLE:    - Low risk of treatment resistance in Down syndrome with Kawasaki disease.

REVISTA / JOURNAL:    - Pediatr Int. 2017 Sep 27. doi: 10.1111/ped.13429.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/ped.13429

AUTORES / AUTHORS: - Takatsuki S; et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Toho University Omori Medical Center.  

RESUMEN / SUMMARY: - Japanese nationwide survey reported that Down syndrome (DS) is less-frequently occurring comorbidity in Kawasaki disease (KD). Although altered immune responses are frequently observed in DS, no studies have focused treatment response and risk for coronary artery abnormalities (CAAs) in DS with KD. The aim of this study was to evaluate clinical manifestations, treatment response and proportion of CAAs in DS with KD. METHODS: We retrospectively reviewed the medical records of DS with KD from 2005 through 2012. The survey questionnaires were sent to facilities nationwide and clinical data regarding KD in DS were collected. Comparable control group included non-DS with KD who were managed at Toho University. RESULTS: Among the 94233 children were diagnosed with acute KD from 2005 to 2012, 16 children with acute KD were DS (0.017%). DS with KD was significantly older than non-DS (median; 8 years vs 1 year, p<0.05, respectively). A half of DS was incomplete KD. Although 50% of DS children were high risk group of immunoglobulin resistance, all children responded to initial treatment and none of patients had CAAs. CONCLUSIONS: All DS with KD were responded to initial IVIG or aspirin therapy despite having high risk of IVIG resistance and none of DS had CAAs. Our finding suggested that the risk of treatment resistance and developing CAAs may be not higher in DS with acute KD.

TÍTULO / TITLE:    - Rapidly progressive pulmonary veno-occlusive disease in an infant with Down syndrome.

REVISTA / JOURNAL:    - Cardiol Young. 2017 Sep;27(7):1402-1405. doi: 10.1017/S1047951117000397.

Enlace a la Editora de la Revista http://dx.doi.org/10.1017/S1047951117000397

AUTORES / AUTHORS: - Muneuchi J; et al.

INSTITUCIÓN / INSTITUTION: - 1Department of Pediatrics,Japan Community Healthcare Organization Kyushu Hospital,Kitakyushu,Japan  

RESUMEN / SUMMARY: - A 4-month-old girl with Down syndrome showed unexpected deterioration of pulmonary hypertension. Despite aggressive pulmonary vasodilation therapy, the patient died at 5 months of age. Lung autopsy showed that the pulmonary veins were obliterated by intimal fibrous thickening, and the media of the veins was arterialised with an increase in elastic fibres. Pulmonary veno-occlusive disease should be considered in the management of individuals with Down syndrome.

TÍTULO / TITLE:    - Should a Down Syndrome Child With a Failing Heart Be Offered Heart Transplantation?

REVISTA / JOURNAL:    - Ann Thorac Surg. 2017 Oct;104(4):1111-1116. doi: 10.1016/j.athoracsur.2017.06.041.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.athoracsur.2017.06.041

AUTORES / AUTHORS: - Kavarana MN; Turnbull JM; Sade RM;

INSTITUCIÓN / INSTITUTION: - Division of Cardiothoracic Surgery, Department of Surgery, Institute of Human Values in Health Care, Medical University of South Carolina, Charleston, South Carolina.   sader@musc.edu

RESUMEN / SUMMARY: -

TÍTULO / TITLE:    - Down syndrome and transposition of the great arteries.

REVISTA / JOURNAL:    - Cardiol Young. 2017 Oct;27(8):1630-1632. doi: 10.1017/S1047951117000774.

Enlace a la Editora de la Revista http://dx.doi.org/10.1017/S1047951117000774

AUTORES / AUTHORS: - McCrossan B; McCay N

INSTITUCIÓN / INSTITUTION: - Paediatric Cardiology Clark Clinic,Royal Belfast Hospital for Sick Children,Belfast,BT12 6BE,Northern Ireland.  

RESUMEN / SUMMARY: - There is an old adage in paediatric cardiology that, despite the high prevalence and wide spectrum of CHD, transposition of the great arteries does not occur in trisomy 21. We present a case of transposition of the great arteries, ventricular septal defect, and pulmonary stenosis in a patient with trisomy 21.

TÍTULO / TITLE:    - Current Surgical Outcomes of Congenital Heart Surgery for Patients With Down Syndrome in Japan.

REVISTA / JOURNAL:    - Circ J. 2017 Sep 12. doi: 10.1253/circj.CJ-17-0483.

Enlace a la Editora de la Revista http://dx.doi.org/10.1253/circj.CJ-17-0483

AUTORES / AUTHORS: - Hoashi T; et al

INSTITUCIÓN / INSTITUTION: - The Japan Cardiovascular Surgery Database Organization.  

RESUMEN / SUMMARY: - BACKGROUND: Current surgical outcomes of congenital heart surgery for patients with Down syndrome are unclear.Methods and Results:Of 29,087 operations between 2008 and 2012 registered in the Japan Congenital Cardiovascular Surgery Database (JCCVSD), 2,651 were carried out for patients with Down syndrome (9%). Of those, 5 major biventricular repair procedures [ventricular septal defect repair (n=752), atrioventricular septal defect repair (n=452), patent ductus arteriosus closure (n=184), atrial septal defect repair (n=167), tetralogy of Fallot (TOF) repair (n=108)], as well as 2 major single ventricular palliations [bidirectional Glenn (n=21) and Fontan operation (n=25)] were selected and their outcomes were compared. The 90-day and in-hospital mortality rates for all 5 major biventricular repair procedures and bidirectional Glenn were similarly low in patients with Down syndrome compared with patients without Down syndrome. On the other hand, mortality after Fontan operation in patients with Down syndrome was significantly higher than in patients without Down syndrome (42/1,558=2.7% vs. 3/25=12.0%, P=0.005). CONCLUSIONS: Although intensive management of pulmonary hypertension is essential, analysis of the JCCVSD revealed favorable early prognostic outcomes after 5 major biventricular procedures and bidirectional Glenn in patients with Down syndrome. Indication of the Fontan operation for patients with Down syndrome should be carefully decided.

TÍTULO / TITLE:    - Pulmonary vascular disease in a failed Fontan patient with Down’s syndrome.

REVISTA / JOURNAL:    - Gen Thorac Cardiovasc Surg. 2017 Aug 10. doi: 10.1007/s11748-017-0809-6.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s11748-017-0809-6

AUTORES / AUTHORS: - Aoki M; et al.

INSTITUCIÓN / INSTITUTION: - Department of Cardiovascular Surgery, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.   masaya5492@gmail.com

RESUMEN / SUMMARY: - It is well known that Down’s syndrome is a strong risk factor for mortality after Fontan operations. We performed two lung biopsies in a Down’s syndrome patient who underwent staged Fontan operations. The pathological findings revealed severe pulmonary arterial hypertrophy and a quantitative real-time polymerase chain reaction revealed the overexpression of endothelin and a decline in the eNOS level at the Fontan operation. Although the preoperative hemodynamic studies revealed that all of the criteria for Fontan had been fulfilled, the patient died of acute cardiac insufficiency, 35 days after the Fontan operation.

DENTAL - DENTAL

TÍTULO / TITLE:    - Growth of the hard palate in infants with Down syndrome compared with healthy infants-A retrospective case control study.

REVISTA / JOURNAL:    - PLoS One. 2017 Aug 10;12(8):e0182728. doi: 10.1371/journal.pone.0182728. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1371/journal.pone.0182728

AUTORES / AUTHORS: - Klingel D; et al

INSTITUCIÓN / INSTITUTION: - Dental Office Dres. Pape, Rheda-Wiedenbruck, Germany.  

RESUMEN / SUMMARY: - OBJECTIVE: To investigate morphological differences of the hard palate in infants with Down syndrome (DS) compared with a volumetric-matched control group (CG). METHODS: Trial design: retrospective case control study. Based on inclusion and exclusion criteria, plaster casts of edentulous maxillae of 40 DS infants (20 females and 20 males, aged 221.3 +/- 132.4 days) and 40 CG infants (20 females and 20 males, aged 53.9 +/- 87.2 days) were digitized and converted into 3-dimensional stereolithography data. An automated landmark- and investigator-independent method for assessing two-dimensional measurements such as width, depth, and length of palate, as well as palatal index and the 3-dimensional volume, were used. RESULTS: Matching DS and healthy CG infants by age, we found reduced sizes in all linear and volumetric measurements in the DS group. Matching both groups by palatal volume, we found no differences between the groups according to palatal width (p = .93), palatal depth (p = .32), and palatal index (p = .31). Control infants with the same palatal volume compared with the DS infants were about 151 days younger, 95%-CI = [102, 200] (Hodges-Lehmann estimator). Except for palatal length and palatal volume, the growth pattern of DS palates decreased irregularly at age 6 to 9 months. CONCLUSIONS: The palate of DS infants in the first 6 to 9 month of life is of normal shape but considerably smaller compared with healthy normals. From 6 to 9 months onward, the growth pattern of the hard palate in DS infants decreases irregularly. High-arch-constricted palates could, therefore, be interpreted as secondarily acquired in later life. We therefore speculate that it could be advantageous to begin oral muscular stimulating therapy between 6 and 9 months of age which may prevent palatal shape alterations and enhance oral function which also contributes to maxillary development.

DERMATOLOGY - DERMATOLOGÍA

TÍTULO / TITLE:    - A 12-year-old Girl with Severe Plaque Psoriasis and Down Syndrome Treated Successfully with Etanercept

REVISTA / JOURNAL:    - Acta Dermatovenerol Croat. 2017 Jul;25(2):155-158.

AUTORES / AUTHORS: - Adamczyk M; et al.

INSTITUCIÓN / INSTITUTION: - Michal Adamczyk, MD, Department of Dermatology, Venerology and Paediatric Dermatology Medical University of Lublin, Radziwillowska 13, 20-080 Lublin, Poland   michaladamczyk1310@wp.pl

RESUMEN / SUMMARY: - The association between Down syndrome and psoriasis is unclear. Immunological abnormalities that present in individuals with Down syndrome result in mild immune debilitation, thus the risk of infectious complications during immunosuppressive therapy might be higher in this group of patients. We present a case of 12-year-old girl with severe plaque psoriasis and Down syndrome, who was initially treated with cyclosporine with good response. However, the drug was withdrawn due to massive viral warts development and loss of efficacy. Afterwards, the girl was treated with etanercept in short 10 week and long 24 week courses with excellent response. The presented case is the first report of a child with Down syndrome and concomitant severe plaque psoriasis treated successfully with etanercept.

TÍTULO / TITLE:    - Hidradenitis Suppurativa and Concomitant Down Syndrome: Literature Review of Other Associated Mucocutaneous Manifestations in Adults.

REVISTA / JOURNAL:    - Skinmed. 2017 Aug 1;15(4):253-258. eCollection 2017.

AUTORES / AUTHORS: - Sehgal VN; et al

INSTITUCIÓN / INSTITUTION: - DermatoVenereology (Skin/VD) Centre, Sehgal Nursing Home, Panchwati, Delhi, India   drsehgal@ndf.vsnl.net.in

RESUMEN / SUMMARY: - This contribution describes hidradenitis suppurativa (HS) occurring in Down disease that presented with morphology conforming to an overlap of stages 1 and 2 of the Hurley staging system, namely the formation of solitary or multiple isolated abscesses without scarring or sinus tracts, recurrent abscesses, and single or multiple widely separated lesions with sinus tract formation, occupying apocrine sweat gland-bearing areas: the inner thighs, groin, and buttocks. The lesions were bilateral and symmetrical, of rare occurrence. In addition, the clinical and pathognomonic features of several other concomitant diseases are defined and reviewed; these include elastosis perforans serpiginosa, fissured tongue/macroglossia, syringomas, palmoplantar keratodermas, cheilitis, xerosis, atopic dermatitis, seborrheic dermatitis, vitiligo, cutis marmorata, and alopecia areata.

EAR/NASAL - OTORRINOLARINGOLOGÍA

TÍTULO / TITLE:    - Tonsillectomy in Children with Down Syndrome: A National Cohort of Inpatients.

REVISTA / JOURNAL:    - Otolaryngol Head Neck Surg. 2017 Sep;157(3):499-503. doi: 10.1177/0194599817711377. Epub 2017 Aug 1.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0194599817711377

AUTORES / AUTHORS: - Baker AB

INSTITUCIÓN / INSTITUTION: - 1 Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon, USA.  

RESUMEN / SUMMARY: - Objective To describe the cost, length of stay, and incidence of postoperative hemorrhage associated with Down syndrome (DS) patients undergoing tonsillectomy in a national sample of inpatient children. Study Design This study uses a national cross-sectional cohort to analyze children with and without DS undergoing tonsillectomy with or without adenoidectomy. Setting 2012 Healthcare Cost and Utilization Project Kids’ Inpatient Database. Subjects and Methods The database was analyzed for postoperative hemorrhage and respiratory compromise, length of stay, and total charges of hospital stay. These outcomes were compared between patients with DS vs patients without DS. Results In total, 7512 patients were identified who underwent tonsillectomy: 7159 patients without DS and 353 patients with DS. The non-DS group was younger with a median age of 3 years (range, 0-18) compared with a DS median age of 4 years (range, 0-20), P = .004. The DS group had a significant increase in postoperative hemorrhage compared with non-DS (10 [2.8%] vs 87 [1.2%], respectively), P = .024. However, the DS and non-DS groups were comparable for respiratory complications (5 [1.4%] vs 106 [1.5%], respectively), P = .922. Median length of stay was significantly increased in the DS group (1 [interquartile range (IQR), 1-3]) compared with the non-DS group (1 [IQR, 1-2]), P < .001. Median charges for hospital stay totaled $17,451 (IQR, $11,901-$24,949) for the DS group compared with $14,395 (IQR, $9739-$21,890) for the non-DS group, P < .001. Conclusion Across the United States, children with DS hospitalized for tonsillectomy have an increased length of stay and cost of care. These data also suggest an increased risk of postoperative hemorrhage during the initial admission without an increased risk of respiratory complications.

TÍTULO / TITLE:    - Otolaryngologic management of Down syndrome patients: what is new?

REVISTA / JOURNAL:    - Curr Opin Otolaryngol Head Neck Surg. 2017 Sep 14. doi: 10.1097/MOO.0000000000000415.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/MOO.0000000000000415

AUTORES / AUTHORS: - Bassett EC; Musso MF

INSTITUCIÓN / INSTITUTION: - aBaylor College of Medicine, Otolaryngology and Head and Neck Surgery bPediatric Otolaryngology and Head and Neck Surgery, Texas Children’s Hospital, Houston, Texas, USA.  

RESUMEN / SUMMARY: - PURPOSE OF REVIEW: The management of children with Down syndrome as it pertains to the otolaryngologist continues to evolve. Obstructive sleep apnea (OSA) has dominated the recent literature, but other topics including hearing loss, swallowing, and perioperative considerations are also reported. RECENT FINDINGS: The prevalence of OSA in children with Down syndrome ranges from 57 to 73% in certain cohorts, and, whereas adentonsillectomy can decrease Apnea-Hypopnea Index, up to 80% may have persistent OSA. Surgical techniques involving reduction of the base of tongue are effective for those who fail adenotonsillectomy, and it is expected that drug-induced sleep endoscopy may improve outcomes. New technology is also on the horizon that can assist with diagnosis and treatment including computational modelling and upper airway stimulation. Children with Down syndrome may not respond to medical management of eustachian tube dysfunction as well as normally developing children. In addition, there is a high prevalence of inner ear anomalies, increasing the risk for sensorineural hearing loss. SUMMARY: Questions remain pertinent to the otolaryngologist regarding the ideal management of children with Down syndrome. Additional studies are necessary, to optimize understanding and treatment of this complex population, in particular as opportunities develop with technological advances.

TÍTULO / TITLE:    - Assessment of weight gain following adenotonsillectomy in children with Down syndrome.

REVISTA / JOURNAL:    - Int J Pediatr Otorhinolaryngol. 2017 Sep;100:103-106. doi: 10.1016/j.ijporl.2017.06.029. Epub 2017 J

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ijporl.2017.06.029

AUTORES / AUTHORS: - D’Esposito CF; et al.

INSTITUCIÓN / INSTITUTION: - Medical University of South Carolina, Department of Otolaryngology - Head and Neck Surgery, United States.   daesposi@musc.edu

RESUMEN / SUMMARY: - Adenotonsillectomy (T&A) has been associated with postoperative weight gain in children. The purpose of this study is to determine whether a similar association exists in children with Down syndrome (DS). METHODS: The medical records of 311 DS patients were reviewed. Subjects were classified into either a control group or surgical group based on whether they had undergone adenotonsillectomy (T&A). Subjects were excluded if they only had one recorded BMI. Cases were analyzed in a pairwise fashion to maximize available data. 113 total patients with DS were identified: 84 (74.3%) in the control group and 29 (25.7%) in the T&A group. Height, weight, BMI, and Z-score data were compared between the control and T&A groups at 6-month intervals over a 24-month period. RESULTS: Children with DS who underwent T&A were comparable by demographics to children with DS who did not undergo T&A. Mean weight gain at 24 months for the T&A group was 8.07 +/- 5.66 kg compared with 5.76 +/- 13.20 kg in controls. The median Z-score at 24 months for the T&A group was 1.11 (0.10-1.88) compared with 1.17 (0.80-1.75) in controls. Children undergoing T&A had a stable median Z-score change of 0.09 at 24 months (p = 0.861, compared to baseline) while children who did not undergo T&A had a significantly increased median Z-score of 0.52 (p = 0.035, compared to baseline). Despite this, there were no significant intergroup differences between weight change, BMI, nor Z-score at any interval (p > 0.05). CONCLUSIONS AND RELEVANCE: Children with DS did not have an increased rate of weight gain or increased BMI after T&A. BMI Z-scores were shown to stabilize over 24 months in the T&A group and increase in the control group. While this suggests that T&A provides an added benefit of weight control in patients with DS, the results should be interpreted with caution due to the small sample size and the fact that not all patients had complete follow up across a 24-month period.

TÍTULO / TITLE:    - Understanding Hearing and Hearing Loss in Children With Down Syndrome.

REVISTA / JOURNAL:    - Am J Audiol. 2017 Sep 18;26(3):301-308. doi: 10.1044/2017_AJA-17-0010.

Enlace a la Editora de la Revista http://dx.doi.org/10.1044/2017_AJA-17-0010

AUTORES / AUTHORS: - Nightengale E; et al. Yoon P

INSTITUCIÓN / INSTITUTION: - Children’s Hospital Colorado and University of Colorado, Aurora.  

RESUMEN / SUMMARY: - This study evaluated the prevalence of permanent and transient hearing loss, the use of hearing aids as a recommendation, and middle ear dysfunction in children with Down syndrome (DS) through a large multiage and ethnically diverse sample, using current audiologic testing practices. Method: Retrospective analysis of data collected on 308 children with DS (168 boys, 140 girls; average age = 5.99 +/- 4.88 years) who received an audiological evaluation during 2013 as part of their medical care at a large pediatric hospital. Results: Permanent hearing loss was identified in 24.9% of the children, among whom bilateral (75.4%) and conductive (33.3%) hearing losses occurred most often. Of children with DS, 22%-30% experienced a transient hearing loss, with a high incidence of middle ear pathologies from infancy until early adulthood. There were no statistical differences between ethnicity and permanent/transient hearing loss diagnosis. Twenty-three percent were current hearing aid users or had them recommended in a treatment plan. Conclusions: The prevalence of hearing loss and abnormal middle ear status is high in the pediatric population with DS. Audiologic evaluations should follow the American Academy of Pediatrics practice guidelines to monitor this high-risk population, and amplification should be considered as an appropriate intervention option if repeated audiologic examinations reveal hearing loss.

ENDOCRINOLOGY/NUTRITION - ENDOCRINOLOGÍA/NUTRICIÓN

TÍTULO / TITLE:    - Down Syndrome-Associated Diabetes Is Not Due To a Congenital Deficiency in beta Cells.

REVISTA / JOURNAL:    - J Endocr Soc. 2017 Jan 1;1(1):39-45. doi: 10.1210/js.2016-1042. Epub 2017 Jan 12.

Enlace a la Editora de la Revista http://dx.doi.org/10.1210/js.2016-1042

AUTORES / AUTHORS: - Butler AE; et al.

INSTITUCIÓN / INSTITUTION: - Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095.  

RESUMEN / SUMMARY: - AIMS/HYPOTHESIS: We sought to establish whether the increased incidence of diabetes associated with Down syndrome was due to a congenital deficit in beta cells. METHODS: The pancreas was obtained at autopsy from nondiabetic subjects with Down syndrome (n = 29) and age-matched nondiabetic control subjects without Down syndrome (n = 28). The pancreas sections were evaluated for the fractional beta-cell area. RESULTS: No difference was found in the fractional beta-cell area between the subjects with Down syndrome and the control subjects. CONCLUSIONS/INTERPRETATIONS: The increased incidence and prevalence of diabetes in individuals with Down syndrome is not due to an underlying congenital deficiency of beta cells.

TÍTULO / TITLE:    - Physical activity and bone mineral density at the femoral neck subregions in adolescents with Down syndrome.

REVISTA / JOURNAL:    - J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1075-1082. doi: 10.1515/jpem-2017-0024.

Enlace a la Editora de la Revista http://dx.doi.org/10.1515/jpem-2017-0024

AUTORES / AUTHORS: - Matute-Llorente A; et al., Casajus.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Low bone mineral density (BMD) has been frequently described in subjects with Down syndrome (DS). Reduced physical activity (PA) levels may contribute to low BMD in this population. The objective of the study was to investigate whether PA levels were related to the femoral neck bone mass distribution in a sample of 14 males and 12 females with DS aged 12-18 years. METHODS: BMD was evaluated by dual energy X-ray absorptiometry (DXA) at the integral, superolateral and inferomedial femoral neck regions and PA levels were assessed by accelerometry. The BMDs between the sexes and PA groups (below and above the 50th percentile of the total PA) were compared using independent t-tests and analyses of covariance (ANCOVAs) controlling for age, height and body weight. RESULTS: No differences were found between the BMDs of males and females in any femoral neck region (p>0.05). Females with higher PA levels demonstrated increased integral (0.774 g/cm2 vs. 0.678 g/cm2) and superolateral femoral neck BMDs (0.696 g/cm2 vs. 0.595 g/cm2) compared to those with lower PA levels (p<0.05). In males, no differences (p<0.05) were found in the BMDs between the PA groups. CONCLUSIONS: This investigation shows that females accumulating more total PA presented increased BMDs at the integral and superolateral femoral neck regions (14.1% and 17.0%, respectively) when compared to their less active peers. These data highlight the importance of PA in females with DS to counteract their low bone mass and to improve their bone health.

TÍTULO / TITLE:    - Evaluation of uric acid levels, thyroid function, and anthropometric parameters in Japanese children with Down syndrome.

REVISTA / JOURNAL:    - J Clin Biochem Nutr. 2017 Sep;61(2):146-152. doi: 10.3164/jcbn.17-55. Epub 2017 Aug 18.

Enlace a la Editora de la Revista http://dx.doi.org/10.3164/jcbn.17-55

AUTORES / AUTHORS: - Niegawa T; et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan.  

RESUMEN / SUMMARY: - Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort.

EPIDEMIOLOGY - EPIDEMIOLOGÍA

TÍTULO / TITLE:    - Estimation of live birth and population prevalence of Down syndrome in nine U.S. states.

REVISTA / JOURNAL:    - : Am J Med Genet A. 2017 Oct;173(10):2710-2719. doi: 10.1002/ajmg.a.38402. Epub 2017 Aug 16.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38402

AUTORES / AUTHORS: - de Graaf G

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

RESUMEN / SUMMARY: - For all of the U.S. states with sufficient data, we estimated live birth and population prevalences for Down syndrome (DS). As social service resources vary between states, such data are important for public policy discussions and state planning. We predicted the actual and nonselective live birth prevalence, and population prevalence, for DS in nine U.S. states based on publicly available datasets from the Centers for Disease Control and Prevention and the Integrated Public Use Microdata Series. As of 2010, we estimated a population size for people with DS of 4,554 in MA (population prevalence 1 in 1,440), 6,101 in NJ (1 in 1,443), 14,315 in NY (1 in 1,355), 9,739 in IL (1 in 1,319), 4,354 in IN (1 in 1,491), 7,295 in MI (1 in 1,354), 9,099 in FL (1 in 2,071), 3,014 in KY (1 in 1,442), and 3,596 in AZ (1 in 1,784). The number of people living with DS has steadily increased from 1950 until 2010 in these nine U.S. states. Population prevalence would have been higher absent DS-related elective terminations. Racial and ethnic groups, other than non-Hispanic whites, comprise a growing proportion within these DS communities, particularly among younger-aged persons.

GASTROENTEROLOGY - GASTROENTEROLOGÍA

TÍTULO / TITLE:    - Screening of celiac disease in Down syndrome - Old and new dilemmas.

REVISTA / JOURNAL:    - World J Clin Cases. 2017 Jul 16;5(7):264-269. doi: 10.12998/wjcc.v5.i7.264.

Enlace a la Editora de la Revista http://dx.doi.org/10.12998/wjcc.v5.i7.264

AUTORES / AUTHORS: - Pavlovic M; et al.

INSTITUCIÓN / INSTITUTION: - Momcilo Pavlovic, Karolina Berenji, Marko Bukurov, College of Vocational Studies in Subotica, 24000 Subotica, Serbia.  

RESUMEN / SUMMARY: - Celiac disease (CD) is a common and well defined autoimmune disorder caused by gliadin and related proteins of wheat, rye, and barley. Epidemiologic studies confirmed that CD is highly associated with other autoimmune diseases and with Down syndrome (DS). The symptomatic form of CD in patients with DS is more frequent than asymptomatic forms. However, growth impairment, anemia, intermittent diarrhea, and constipation are symptoms and signs typically of children with DS without CD. Late identification of the disease can lead to various complications, sometimes even very severe. Therefore, systematic screening for CD is essential in the management of children and adolescents with DS. Many medical organizations recommend screening in this group of patients. However, current policy statements vary in their recommendations for screening and there is still a need for establishing uniform diagnostic criteria.

GENETICS - GENÉTICA

TÍTULO / TITLE:    - The Influence of trisomy 21 on facial form and variability.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Sep 21. doi: 10.1002/ajmg.a.38464.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38464

AUTORES / AUTHORS: - Starbuck JM Cole TM 3rd; Reeves RH; Richtsmeier JT

INSTITUCIÓN / INSTITUTION: - Department of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri.  

RESUMEN / SUMMARY: - Triplication of chromosome 21 (trisomy 21) results in Down syndrome (DS), the most common live-born human aneuploidy. Individuals with DS have a unique facial appearance that can include form changes and altered variability. Using 3D photogrammatic images, 3D coordinate locations of 20 anatomical landmarks, and Euclidean Distance Matrix Analysis methods, we quantitatively test the hypothesis that children with DS (n = 55) exhibit facial form and variance differences relative to two different age-matched (4-12 years) control samples of euploid individuals: biological siblings of individuals with DS (n = 55) and euploid individuals without a sibling with DS (n = 55). Approximately 36% of measurements differ significantly between DS and DS-sibling samples, whereas 46% differ significantly between DS and unrelated control samples. Nearly 14% of measurements differ significantly in variance between DS and DS sibling samples, while 18% of measurements differ significantly in variance between DS and unrelated euploid control samples. Of those measures that showed a significant difference in variance, all were relatively increased in the sample of DS individuals. These results indicate that faces of children with DS are quantitatively more similar to their siblings than to unrelated euploid individuals and exhibit consistent, but slightly increased variation with most individuals falling within the range of normal variation established by euploid samples. These observations provide indirect evidence of the strength of the genetic underpinnings of the resemblance between relatives and the resistance of craniofacial development to genetic perturbations caused by trisomy 21, while underscoring the complexity of the genotype-phenotype map.

TÍTULO / TITLE:    - Analysis of Taurine’s Anti-Down Syndrome Potential in Caenorhabditis elegans.

REVISTA / JOURNAL:    - Adv Exp Med Biol. 2017;975:1113-1128. doi: 10.1007/978-94-024-1079-2_89.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/978-94-024-1079-2_89

AUTORES / AUTHORS: - Ko YJ; Lee DH;

INSTITUCIÓN / INSTITUTION: - Department of Life Sciences, University of Seoul, Seoul, 02504, South Korea.   leedh@uos.ac.kr

RESUMEN / SUMMARY: - Down syndrome (DS) patients overexpress human DS critical region gene 1 (hDSCR-1), whose translational product inhibits calcineurin-dependent signaling pathways of genetic transcription. Compared to hDSCR-1, C. elegans rcn-1 has 40% sequence similarity and its proteins share an analogous function with hDSCR-1 in regulating calcineurin. Taurine has had a positive effect on DS patients. According to animal research studies, taurine reduces the expression of MCIP1, a calcineurin inhibitory protein, on C2C12 myotubes and fibroblast in mouse. This study utilizes two C. elegans models for DS: rcn-1 overexpression model, displaying a calcineurin-deficient phenotype, and calcineurin loss-of function mutants. C. elegans larvae were treated with taurine to characterize its effect and mechanism in helping DS patients. RCN-1 expression and behavioral changes were examined in rcn-1 overexpression and calcineurin-deficient models at different concentrations of taurine. When treated with taurine, transgenic worms harboring an rcn-1 reporter (RCN-1::GFP) showed a reduced level of rcn-1 mRNA expression and improved behaviors that were comparable to those in the wild type. These results indicate that taurine exerts a down-regulating effect on the expression of rcn-1 and, consequently, a positive effect on the expression of calcineurins. In summary, taurine may improve the DS symptoms by prompting a positive interaction between RCN-1 and calcineurin. Furthermore, these results suggest that novel mechanisms may regulate interactions among taurine, RCN-1 and calcineurin.

TÍTULO / TITLE:    - Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

REVISTA / JOURNAL:    - Genet Mol Res. 2017 Aug 17;16(3). doi: 10.4238/gmr16039738.

Enlace a la Editora de la Revista http://dx.doi.org/10.4238/gmr16039738

AUTORES / AUTHORS: - Mattos MF; Pavarino EC; et al

INSTITUCIÓN / INSTITUTION: - Unidade de Pesquisa em Genetica e Biologia Molecular Brasil   erika@famerp.br

RESUMEN / SUMMARY: - Down syndrome (DS) individuals present impaired adaptive immune system. However, the etiology of the immunological deficiency in these individuals is not completely understood. This study investigated the frequency of interleukin 6 polymorphisms (rs1800795, rs1800796, and rs1800797) in individuals with DS and individuals without the syndrome. The study included 282 individuals, 94 with DS attended at the General Genetics Outpatient Service of Hospital de Base, Sao Jose do Rio Preto, SP, Brazil, and 188 individuals without DS attended at the Pediatric Service of Hospital de Base de Sao Jose do Rio Preto, SP, Brazil. Genotyping was performed by allelic discrimination technique by real-time polymerase chain reaction using TaqMan SNP Genotyping Assays (Applied Biosystems). There was no difference in the genotype frequency between individuals with and without DS for the evaluated polymorphisms (P > 0.05). The frequency of interleukin 6 polymorphisms did not differ significantly between individuals with and without DS in the casuistic analyzed.

TÍTULO / TITLE:    - Why could a woman have three Trisomy 21 pregnancies? - a case report.

REVISTA / JOURNAL:    - Clin Case Rep. 2017 Jun 15;5(8):1222-1225. doi: 10.1002/ccr3.997. eCollection 2017 Aug.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ccr3.997

AUTORES / AUTHORS: - Magalhaes M; Marques C; et al

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology AServico de Ginecologia e ObstetriciaCentro Hospitalar e Universitario de CoimbraCoimbraPortugal.  

RESUMEN / SUMMARY: - Mosaicism, an important cause for recurrent T21, should be suspected in families with more than one affected child wishing to receive prenatal counseling. Fluorescence in-situ hybridization analysis in a large number of cells and in different tissue samples is critical for detecting low-level mosaicism and is a key prognostic factor.

TÍTULO / TITLE:    - A microRNA cluster (let-7c, miRNA-99a, miRNA-125b, miRNA-155 and miRNA-802) encoded at chr21q21.1-chr21q21.3 and the phenotypic diversity of Down’s syndrome (DS; trisomy 21).

REVISTA / JOURNAL:    - J Nat Sci. 2017 Sep;3(9). pii: e446.

AUTORES / AUTHORS: - Zhao Y; et al

INSTITUCIÓN / INSTITUTION: - Department of Anatomy and Cell Biology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.;  

RESUMEN / SUMMARY: - Down’s syndrome (DS) is the most common genetic cause of intellectual disability and cognitive deficit attributable to a naturally-occurring abnormality of gene dosage. DS is caused by a triplication of all or part of human chromosome 21 (chr21) and currently there are no effective treatments for this incapacitating disorder of neurodevelopment. First described by the English physician John Langdon Down in 1862, propelled by the invention of karyotype analytical techniques in the early 1950s and the discovery in 1959 by the French geneticist Jerome Lejune that DS resulted from an extra copy of chr21, DS was the first neurological disorder linking a chromosome dosage imbalance to a defect in intellectual development with ensuing cognitive disruption. Especially over the last 60 years, it has been repeatedly demonstrated that DS is not an easily defined disease entity but rather possesses a remarkably wide variability in the ‘phenotypic spectrum’ associated with this trisomic disorder. This commentary describes the presence of a 5 member cluster of chr21-encoded microRNAs (miRNAs) that includes let-7c, miRNA-99a, miRNA-125b, miRNA-155 and miRNA-802 located on the long arm of human chr21, spanning the chr21q21.1-chr21q21.3 region and flanking the beta amyloid precursor (betaAPP) gene, and reviews the potential contribution of these 5 miRNAs to the remarkably diverse DS phenotype.

GROWTH/DEVELOPMENT - CRECIMIENTO/DESARROLLO

TÍTULO / TITLE:    - The Influence of trisomy 21 on facial form and variability.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Sep 21. doi: 10.1002/ajmg.a.38464.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38464

AUTORES / AUTHORS: - Starbuck JM Cole TM 3rd; Reeves RH; Richtsmeier JT

INSTITUCIÓN / INSTITUTION: - Department of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri.  

RESUMEN / SUMMARY: - Triplication of chromosome 21 (trisomy 21) results in Down syndrome (DS), the most common live-born human aneuploidy. Individuals with DS have a unique facial appearance that can include form changes and altered variability. Using 3D photogrammatic images, 3D coordinate locations of 20 anatomical landmarks, and Euclidean Distance Matrix Analysis methods, we quantitatively test the hypothesis that children with DS (n = 55) exhibit facial form and variance differences relative to two different age-matched (4-12 years) control samples of euploid individuals: biological siblings of individuals with DS (n = 55) and euploid individuals without a sibling with DS (n = 55). Approximately 36% of measurements differ significantly between DS and DS-sibling samples, whereas 46% differ significantly between DS and unrelated control samples. Nearly 14% of measurements differ significantly in variance between DS and DS sibling samples, while 18% of measurements differ significantly in variance between DS and unrelated euploid control samples. Of those measures that showed a significant difference in variance, all were relatively increased in the sample of DS individuals. These results indicate that faces of children with DS are quantitatively more similar to their siblings than to unrelated euploid individuals and exhibit consistent, but slightly increased variation with most individuals falling within the range of normal variation established by euploid samples. These observations provide indirect evidence of the strength of the genetic underpinnings of the resemblance between relatives and the resistance of craniofacial development to genetic perturbations caused by trisomy 21, while underscoring the complexity of the genotype-phenotype map.

TÍTULO / TITLE:    - Physical activity and bone mineral density at the femoral neck subregions in adolescents with Down syndrome.

REVISTA / JOURNAL:    - J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1075-1082. doi: 10.1515/jpem-2017-0024.

Enlace a la Editora de la Revista http://dx.doi.org/10.1515/jpem-2017-0024

AUTORES / AUTHORS: - Matute-Llorente A; et al., Casajus.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Low bone mineral density (BMD) has been frequently described in subjects with Down syndrome (DS). Reduced physical activity (PA) levels may contribute to low BMD in this population. The objective of the study was to investigate whether PA levels were related to the femoral neck bone mass distribution in a sample of 14 males and 12 females with DS aged 12-18 years. METHODS: BMD was evaluated by dual energy X-ray absorptiometry (DXA) at the integral, superolateral and inferomedial femoral neck regions and PA levels were assessed by accelerometry. The BMDs between the sexes and PA groups (below and above the 50th percentile of the total PA) were compared using independent t-tests and analyses of covariance (ANCOVAs) controlling for age, height and body weight. RESULTS: No differences were found between the BMDs of males and females in any femoral neck region (p>0.05). Females with higher PA levels demonstrated increased integral (0.774 g/cm2 vs. 0.678 g/cm2) and superolateral femoral neck BMDs (0.696 g/cm2 vs. 0.595 g/cm2) compared to those with lower PA levels (p<0.05). In males, no differences (p<0.05) were found in the BMDs between the PA groups. CONCLUSIONS: This investigation shows that females accumulating more total PA presented increased BMDs at the integral and superolateral femoral neck regions (14.1% and 17.0%, respectively) when compared to their less active peers. These data highlight the importance of PA in females with DS to counteract their low bone mass and to improve their bone health.

TÍTULO / TITLE:    - Attainment of gross motor milestones in children with Down syndrome in Kosovo - developmental perspective.

REVISTA / JOURNAL:    - Med Glas (Zenica). 2017 Aug 1;14(2):189-198. doi: 10.17392/917-17.

Enlace a la Editora de la Revista http://dx.doi.org/10.17392/917-17

AUTORES / AUTHORS: - Beqaj S; et al

INSTITUCIÓN / INSTITUTION: - Department of Physiotherapy, School of Medicine, University of Prishtina, Prishtina, Republic of Kosovo; School of Physical Education, Sport and Health, Ss. Cyril and Methodius University in Skopje, Skopje, Republic of Macedonia.  

RESUMEN / SUMMARY: - Aim To investigate the age (in months) at which motor skills are developed in children with Down syndrome (DS), and compare it to the age of the development of the same skills in both, children with typical development (TD), and children with DS reported by four other studies. Methods Sixteen children (7 girls and 9 boys) were monthly assessed for the development of nineteen motor skills between 2008 and 2011. The mean ages when the skills were accomplished were presented using descriptive statistics. Independent T-samples test (significance < 0.05) was used to compare the mean developmental ages from our study with those seen in children with TD (Comparison 1) and also in children with DS reported by four other authors (Comparison 2a-2d). Results Children with DS developed at a significantly slower pace compared to children with TD (p=0.005). Generally, delay and variance of developmental age in children with DS increased chronologically with the complexity of the skills. No significant difference was found between developmental age in children from the present study and children with DS from other studies. Conclusion The rate of attainment of motor skills is delayed in children with DS in comparison to children with TD, however, the developmental sequence is the same. The delayed development is more prominent in more complex skills.

TÍTULO / TITLE:    - Genome-wide gene expression analysis in the placenta from fetus with trisomy 21.

REVISTA / JOURNAL:    - BMC Genomics. 2017 Sep 12;18(1):720. doi: 10.1186/s12864-017-3993-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12864-017-3993-y

AUTORES / AUTHORS: - Lim JH; Chun SH; et al

INSTITUCIÓN / INSTITUTION: - Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women’s Healthcare Center, Seoul, South Korea.   shchun@ewha.ac.kr

RESUMEN / SUMMARY: - We performed whole human genome expression analysis in placenta tissue (normal and T21) samples in order to investigate gene expression into the pathogenesis of trisomy 21 (T21) placenta. We profiled the whole human genome expression of placental samples from normal and T21 fetuses using the GeneChip Human Genome U133 plus 2.0 array. Based on these data, we predicted the functions of differentially expressed genes using bioinformatics tools. RESULTS: A total of 110 genes had different expression patterns in the T21 placentas than they did in the normal placentas. Among them, 77 genes were up-regulated in the T21 placenta and 33 genes were down-regulated compared to their respective levels in normal placentas. Over half of the up-regulated genes (59.7%, n = 46) were located on HSA21. Up-regulated genes in the T21 placentas were significantly associated with T21 and its complications including mental retardation and neurobehavioral manifestations, whereas down-regulated genes were significantly associated with diseases, such as cystitis, metaplasia, pathologic neovascularization, airway obstruction, and diabetes mellitus. The interactive signaling network showed that 53 genes (40 up-regulated genes and 13 down-regulated genes) were an essential component of the dynamic complex of signaling (P < 1.39e-08). CONCLUSIONS: Our findings provide a broad overview of whole human genome expression in the placentas of fetuses with T21 and a possibility that these genes regulate biological pathways that have been involved in T21 and T21 complications. Therefore, these results could contribute to future research efforts concerning gene involvement in the disease’s pathogenesis.

HEMATOLOGY/ONCOLOGY - HEMATOLOGÍA/ONCOLOGÍA

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;8(33):55760-55765. doi: 10.18632/oncotarget.17406. eCollection 2017 Aug 15.

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:    - Blinatumomab activity in a patient with Down syndrome B-precursor acute lymphoblastic leukemia.

REVISTA / JOURNAL:    - Pediatr Blood Cancer. 2017 Sep 17. doi: 10.1002/pbc.26824.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pbc.26824

AUTORES / AUTHORS: - Wadhwa A; Kutny MA; Xavier AC

INSTITUCIÓN / INSTITUTION: - Division of Hematology/Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.  

RESUMEN / SUMMARY: - Persistent minimal residual disease (MRD) after consolidation may indicate chemotherapy insensitivity in B-precursor acute lymphoblastic leukemia (BP-ALL). Given the strong association of MRD and outcome in non-Down syndrome (non-DS) BP-ALL, it is likely that MRD levels are also of prognostic significance in DS BP-ALL. We report here the successful use of blinatumomab, a bispecific T-cell engager antibody construct, in a patient with DS BP-ALL and persistent MRD at the end of consolidation. Blinatumomab has been shown to have excellent results in patients with relapsed/refractory BP-ALL. This patient had no significant toxicity and achieved MRD negativity after only one cycle of blinatumomab.

TÍTULO / TITLE:    - A unique set of complex chromosomal abnormalities in an infant with myeloid leukemia associated with Down syndrome.

REVISTA / JOURNAL:    - Mol Cytogenet. 2017 Sep 11;10:35. doi: 10.1186/s13039-017-0335-3. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13039-017-0335-3

AUTORES / AUTHORS: - de Souza DC; et al.

INSTITUCIÓN / INSTITUTION: - Cytogenetic Laboratory, Bone Marrow Transplantation Center, National Cancer Institute (INCA), Praca Cruz Vermelha no. 23, 6 degrees andar. Centro, CEP, Rio de Janeiro, RJ 20230-130 Brazil.  

RESUMEN / SUMMARY: - Children with Down syndrome (DS) have an enhanced risk of developing acute leukemia, with the most common subtype being acute megakaryoblastic leukemia (AMKL). Myeloid leukemia in Down syndrome (ML-DS) is considered a disease with distinct clinical and biological features. There are few studies focusing on the clonal cytogenetic changes during evolution of ML-DS. CASE PRESENTATION: Here, we describe a complex karyotype involving a previously unreported set of chromosomal abnormalities acquired during progression of ML-DS in an infant boy: derivative der(1)t(1;15)(q24;q23), translocation t(4;5)(q26;q33) and derivative der(15)t(7;15)(p21;q23). Different molecular cytogenetic probes and probesets including whole chromosome painting (WCP) and locus specific probes, as well as, multicolor-FISH and multicolor chromosome banding (MCB) were performed in order to characterize the chromosomal abnormalities involved in this complex karyotype. The patient was treated according to the acute myeloid leukemia-Berlin-Frankfurt-Munich-2004 (AML-BFM 2004) treatment protocol for patients with Down syndrome; however, he experienced a poor clinical outcome. CONCLUSION: The molecular cytogenetic studies performed, allowed the characterization of novel chromosomal abnormalities in ML-DS and possible candidate genes involved in the leukemogenic process. Our findings suggest that the complex karyotype described here was associated with the poor prognosis.

INFECTIOUS DISEASES - INFECCIONES

TÍTULO / TITLE:    - Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

REVISTA / JOURNAL:    - Paediatr Drugs. 2017 Sep 11. doi: 10.1007/s40272-017-0264-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s40272-017-0264-y

AUTORES / AUTHORS: - Kashiwagi T; Nomoto K;

INSTITUCIÓN / INSTITUTION: - AbbVie GK, Mita 3-5-27, Minato-ku, Tokyo, 108-6302, Japan.   ken.nomoto@abbvie.com

RESUMEN / SUMMARY: - The aim of this study was to assess the safety and effectiveness of palivizumab for the prevention of lower respiratory tract infection (LRI) caused by respiratory syncytial virus (RSV) in children with immunocompromised conditions or Down syndrome. METHODS: In this multicenter, post-marketing surveillance study (December 2013 to December 2015), children aged TÍTULO / TITLE:    - Increased levels of inflammatory plasma markers and obesity risk in a mouse model of Down syndrome.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Sep 25. pii: S0891-5849(17)30774-8. doi:

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.09.021

AUTORES / AUTHORS: - Fructuoso M; et al, Dierssen M;

INSTITUCIÓN / INSTITUTION: - Cellular & Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, España;:   mara.dierssen@crg.eu

RESUMEN / SUMMARY: - Down syndrome (DS) is caused by the trisomy of human chromosome 21 and is the most common genetic cause of intellectual disability. In addition to the intellectual deficiencies and physical anomalies, DS individuals present a higher prevalence of obesity and subsequent metabolic disorders than healthy adults. There is increasing evidence from both clinical and experimental studies indicating the association of visceral obesity with a pro-inflammatory status and recent studies have reported that obese people with DS suffer from low-grade systemic inflammation. However, the link between adiposity and inflammation has not been explored in DS. Here we used Ts65Dn mice, a validated DS mouse model, for the study of obesity-related inflammatory markers. Ts65Dn mice presented increased energy intake, and a positive energy balance leading to increased adiposity (fat mass per body weight), but did not show overweight, which only was apparent upon high fat diet induced obesity. Trisomic mice also had fasting hyperglycemia and hypoinsulinemia, and normal incretin levels. Those trisomy-associated changes were accompanied by reduced ghrelin plasma levels and slightly but not significantly increased leptin levels. Upon a glucose load, Ts65Dn mice showed normal increase of incretins accompanied by over-responses of leptin and resistin, while maintaining the hyperglycemic and hypoinsulinemic phenotype. These changes in the adipoinsular axis were accompanied by increased plasma levels of inflammatory biomarkers previously correlated with obesity galectin-3 and HSP72, and reduced IL-6. Taken together, these results suggest that increased adiposity, and pro-inflammatory adipokines leading to low-grade inflammation are important players in the propensity to obesity in DS. We conclude that DS would be a case of impaired metabolic-inflammatory axis.

MOLECULAR BIOLOGY/BIOCHEMISTRY - BIOLOGÍA MOLECULAR/BIOQUÍMICA

TÍTULO / TITLE:    - Combined association of Presenilin-1 and Apolipoprotein E polymorphisms with maternal meiosis II error in Down syndrome births.

REVISTA / JOURNAL:    - Genet Mol Biol. 2017 Jul-Sep;40(3):577-585. doi: 10.1590/1678-4685-GMB-2016-0138. Epub 2017 Jul 31.

Enlace a la Editora de la Revista http://dx.doi.org/10.1590/1678-4685-GMB-2016-0138

AUTORES / AUTHORS: - Bhaumik P; et al

INSTITUCIÓN / INSTITUTION: - Department of Biotechnology, School of Biotechnology and Biological Sciences. Maulana Abul Kalam Azad University of Technology, West Bengal, India.  

RESUMEN / SUMMARY: - Alzheimer’s disease and Down syndrome often exhibit close association and predictively share common genetic risk-factors. Presenilin-1 (PSEN-1) and Apolipoprotein E (APOE) genes are associated with early and late onset of Alzheimer’s disease, respectively. Presenilin -1 is involved in faithful chromosomal segregation. A higher frequency of the APOE epsilon4 allele has been reported among young mothers giving birth to Down syndrome children. In this study, 170 Down syndrome patients, grouped according to maternal meiotic stage of nondisjunction and maternal age at conception, and their parents were genotyped for PSEN-1 intron-8 and APOE polymorphisms. The control group consisted of 186 mothers of karyotypically normal children. The frequencies of the PSEN-1 T allele and TT genotype, in the presence of the APOE epsilon4 allele, were significantly higher among young mothers (< 35 years) with meiosis II nondisjunction than in young control mothers (96.43% vs. 65.91% P = 0.0002 and 92.86% vs. 45.45% P < 0.0001 respectively) but not among mothers with meiosis I nondisjunction. We infer that the co-occurrence of the PSEN-1 T allele and the APOE epsilon4 allele associatively increases the risk of meiotic segregation error II among young women.

TÍTULO / TITLE:    - Mitochondria as pharmacological targets in Down syndrome.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Aug 31. pii: S0891-5849(17)30730-X. doi: 10.1016/j.freeradbiomed.2017.08.0

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.014

AUTORES / AUTHORS: - Valenti D; et al., Vacca RA;

INSTITUCIÓN / INSTITUTION: - Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy.   r.vacca@ibiom.cnr.it

RESUMEN / SUMMARY: - Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS. DS is associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, molecular mechanisms responsible for mitochondrial damage and energy deficits have been identified and characterized in several DS-derived human cells and animal models of DS. Therefore, therapeutic strategies targeting mitochondria could have great potential for new treatment regimens in DS. The purpose of this review is to highlight recent studies concerning mitochondrial impairment in DS, focusing on alterations of the molecular pathways controlling mitochondrial function. We will also discuss the effects and molecular mechanisms of naturally occurring and chemically synthetized drugs that exert neuroprotective effects through modulation of mitochondrial function and attenuation of oxidative stress. These compounds might represent novel therapeutic tools for the modulation of energy deficits in DS.

TÍTULO / TITLE:    - Association between polymorphisms in folate metabolism genes and maternal risk for Down syndrome: A meta-analysis.

REVISTA / JOURNAL:    - Mol Clin Oncol. 2017 Sep;7(3):367-377. doi: 10.3892/mco.2017.1338. Epub 2017 Jul 24.

Enlace a la Editora de la Revista http://dx.doi.org/10.3892/mco.2017.1338

AUTORES / AUTHORS: - Gu Y;

INSTITUCIÓN / INSTITUTION: - Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.  

RESUMEN / SUMMARY: - Previous studies have focused on the association between polymorphisms of the genes involved in folate metabolism and Down syndrome (DS); however, the results remain inconclusive. The present meta-analysis was conducted to assess the association between RFC-1 A80G/MTR A2756G/CBS 844ins68 polymorphisms and the maternal risk of DS. Published studies were retrieved from PubMed, Embase, China National Knowledge Infrastructure and Chinese Biomedicine databases. Pooled odds ratios (ORs) with 95% confidence interval (CIs) were calculated using the fixed- or random-effects model. Additionally, test of heterogeneity, cumulative meta-analysis, sensitivity analysis and assessment of bias were also performed. Finally, 11, 11 and 6 studies were deemed eligible for meta-analyses of RFC-1 A80G, MTR A2756G and CBS 844ins68, respectively. A significant association between RFC-1 A80G polymorphism and DS risk was observed for G vs. A (OR=1.19, 95% CI: 1.004-1.40, P=0.04) and the recessive model (OR=1.28, 95% CI: 1.05-1.56, P=0.01). In the stratified analysis by source of control or sample size, a significantly increased risk was observed among hospital-based studies and large-sample groups (>200 subjects), respectively. In addition, the cumulative meta-analysis of the RFC-1 A80G variant revealed a trend toward an association as the amount of data increased. However, for the MTR A2756G and CBS 844ins68 polymorphisms, no obvious association was found for all genetic models. In summary, the present meta-analysis demonstrated that RFC-1 A80G, but not MTR A2756G or CBS 844ins68, was considered as a maternal risk factor for DS in the offspring.

NEUROBIOLOGY - NEUROBIOLOGÍA

TÍTULO / TITLE:    - Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice.

REVISTA / JOURNAL:    - Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10268-10273. doi: 10.1073/pnas.1704143114. Epub 2017 S

Enlace a la Editora de la Revista http://dx.doi.org/10.1073/pnas.1704143114

AUTORES / AUTHORS: - Nakano-Kobayashi A; ... Hagiwara M

INSTITUCIÓN / INSTITUTION: - Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan   hagiwara.masatoshi.8c@kyoto-u.ac.jp

RESUMEN / SUMMARY: - Down syndrome (DS) caused by trisomy of chromosome 21 is the most common genetic cause of intellectual disability. Although the prenatal diagnosis of DS has become feasible, there are no therapies available for the rescue of DS-related neurocognitive impairment. A growth inducer newly identified in our screen of neural stem cells (NSCs) has potent inhibitory activity against dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and was found to rescue proliferative deficits in Ts65Dn-derived neurospheres and human NSCs derived from individuals with DS. The oral administration of this compound, named ALGERNON (altered generation of neurons), restored NSC proliferation in murine models of DS and increased the number of newborn neurons. Moreover, administration of ALGERNON to pregnant dams rescued aberrant cortical formation in DS mouse embryos and prevented the development of abnormal behaviors in DS offspring. These data suggest that the neurogenic phenotype of DS can be prevented by ALGERNON prenatal therapy.

TÍTULO / TITLE:    - Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome.

REVISTA / JOURNAL:    - J Neurosci. 2017 Oct 11;37(41):9880-9888. doi: 10.1523/JNEUROSCI.1045-17.2017. Epub 2017 Sep 12.

Enlace a la Editora de la Revista http://dx.doi.org/10.1523/JNEUROSCI.1045-17.2017

AUTORES / AUTHORS: - William CM; et al

INSTITUCIÓN / INSTITUTION: - New York University School of Medicine, Department of Pathology, New York, New York 10016, and   christopher.william@nyumc.org

RESUMEN / SUMMARY: - Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation. This phenotype is similar to that of transgenic mice that express amyloid precursor protein (APP), which is duplicated in DS and in Ts65DN mice; however, normalizing APP gene copy number in Ts65Dn mice fails to rescue plasticity. Ts1Rhr mice harbor a duplication of the telomeric third of the Ts65Dn-duplicated sequence and demonstrate the same ODP defect, suggesting a gene or genes sufficient to drive the phenotype are located in that smaller duplication. In addition, we find that Ts65Dn mice demonstrate an abnormality in olfactory system connectivity, a defect in the refinement of connections to second-order neurons in the olfactory bulb. Ts1Rhr mice do not demonstrate a defect in glomerular refinement, suggesting that distinct genes or sets of genes underlie visual and olfactory system phenotypes. Importantly, these data suggest that developmental plasticity and connectivity are impaired in sensory systems in DS model mice, that such defects may contribute to functional impairment in DS, and that these phenotypes, present in male and female mice, provide novel means for examining the genetic and molecular bases for neurodevelopmental impairment in model mice in vivo SIGNIFICANCE STATEMENT Our understanding of the basis for intellectual impairment in Down syndrome is hindered by the large number of genes duplicated in Trisomy 21 and a lack of understanding of the effect of disease pathology on the function of neural circuits in vivo This work describes early postnatal developmental abnor

TÍTULO / TITLE:    - Inhibition of Drp1-mediated mitochondrial fission improves mitochondrial dynamics and bioenergetics stimulating neurogenesis in hippocampal progenitor cells from a Down syndrome mouse model.

REVISTA / JOURNAL:    - Biochim Biophys Acta. 2017 Sep 19. pii: S0925-4439(17)30329-0. doi: 10.1016/j.bbadis.2017.09.014.

Enlace a la Editora de la Revista Biochim Biophys Acta. 2017 Sep 19. pii: S0925-4439(17)30329-0. doi: 10.1016/j.bbadis.2017.09.014.

AUTORES / AUTHORS: - Valenti D; et al

INSTITUCIÓN / INSTITUTION: - Institute of Biomembranes, Bioenergetics and Molecular Biotechnology, National Council of Research, Bari, Italy.   d.valenti@ibiom.cnr.it

RESUMEN / SUMMARY: - Functional and structural damages to mitochondria have been critically associated with the pathogenesis of Down syndrome (DS), a human multifactorial disease caused by trisomy of chromosome 21 and associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, we demonstrated in neural progenitor cells (NPCs) isolated from the hippocampus of Ts65Dn mice -a widely used model of DS - a severe impairment of mitochondrial bioenergetics and biogenesis and reduced NPC proliferation. Here we further investigated the origin of mitochondrial dysfunction in DS and explored a possible mechanistic link among alteration of mitochondrial dynamics, mitochondrial dysfunctions and defective neurogenesis in DS. We first analyzed mitochondrial network and structure by both confocal and transmission electron microscopy as well as by evaluating the levels of key proteins involved in the fission and fusion machinery. We found a fragmentation of mitochondria due to an increase in mitochondrial fission associated with an up-regulation of dynamin-related protein 1 (Drp1), and a decrease in mitochondrial fusion associated with a down-regulation of mitofusin 2 (Mnf2) and increased proteolysis of optic atrophy 1 (Opa1). Next, using the well-known neuroprotective agent mitochondrial division inhibitor 1 (Mdivi-1), we assessed whether the inhibition of mitochondrial fission might reverse alteration of mitochondrial dynamics and mitochondrial dysfunctions in DS neural progenitors cells. We demonstrate here for the first time, that Mdivi-1 restores mitochondrial network organization, mitochondrial energy production and ultimately improves proliferation and neuronal differentiation of NPCs. This research paves the way for the discovery of new therapeutic tools in managing some DS-associated clinical manifestations.

TÍTULO / TITLE:    - Neurogenesis impairment: An early developmental defect in Down syndrome.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Jul 27. pii: S0891-5849(17)30710-4. doi: 10.1016/j.freeradbiomed.2017.07.0

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.07.026

AUTORES / AUTHORS: - Stagni F; Bartesaghi R; et al

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

RESUMEN / SUMMARY: - Down syndrome (DS) is characterized by brain hypotrophy and intellectual disability starting from early life stages. Accumulating evidence shows that the phenotypic features of the DS brain can be traced back to the fetal period since the DS brain exhibits proliferation potency reduction starting from the critical time window of fetal neurogenesis. This defect is worsened by the fact that neural progenitor cells exhibit reduced acquisition of a neuronal phenotype and an increase in the acquisition of an astrocytic phenotype. Consequently, the DS brain has fewer neurons in comparison with the typical brain. Although apoptotic cell death may be increased in DS, this does not seem to be the major cause of brain hypocellularity. Evidence obtained in brains of individuals with DS, DS-derived induced pluripotent stem cells (iPSCs), and DS mouse models has provided some insight into the mechanisms underlying the developmental defects due to the trisomic condition. Although many triplicated genes may be involved, in the light of the studies reviewed here, DYRK1A, APP, RCAN1 and OLIG1/2 appear to be particularly important determinants of many neurodevelopmental alterations that characterize DS because their triplication affects both the proliferation and fate of neural precursor cells as well as apoptotic cell death. Based on the evidence reviewed here, pathways downstream to these genes may represent strategic targets, for the design of possible interventions.

NEUROLOGY - NEUROLOGÍA

TÍTULO / TITLE:    - Severe Brain Malformations in an Infant With Pyruvate Dehydrogenase Deficiency and Down Syndrome.

REVISTA / JOURNAL:    - Pediatr Neurol. 2017 Oct;75:101-102. doi: 10.1016/j.pediatrneurol.2017.05.002. Epub 2017 May 8.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.pediatrneurol.2017.05.002

AUTORES / AUTHORS: - Chapel-Crespo CC; Prasun P

INSTITUCIÓN / INSTITUTION: - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.   Pankaj.Prasun@mssm.edu

RESUMEN / SUMMARY: -

TÍTULO / TITLE:    - Craniospinal Germinomas in Patient with Down Syndrome Successfully Treated with Standard-Dose Chemotherapy and Craniospinal Irradiation: Case Report and Literature Review.

REVISTA / JOURNAL:    - World Neurosurg. 2017 Sep 12. pii: S1878-8750(17)31530-9. doi: 10.1016/j.wneu.2017.09.024.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.wneu.2017.09.024

AUTORES / AUTHORS: - Miyake Y; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.   ymiyaken@gmail.com

RESUMEN / SUMMARY: - Patients with Down syndrome (DS) are more likely to develop chemotherapy-related complications. The standard treatment for these patients with cancer has not yet been established, and the risks of standard chemotherapy are unclear. In this paper, a rare case of multiple craniospinal germinomas in a patient with DS, which was successfully treated with standard-dose chemotherapy combined with craniospinal irradiation, is reported. CASE DESCRIPTION: The authors report a case of multiple craniospinal germinomas in a DS patient who presented with bilateral oculomotor and facial nerve palsy and hearing loss. The patient underwent 3 courses of combination chemotherapy using a standard dose of carboplatin and etoposide and 23.4 Gy of concurrent craniospinal irradiation. Posttreatment magnetic resonance imaging showed reduction of the tumors. Both fluorodeoxyglucose- and methionine-positron emission tomography demonstrated no uptake in the residual tumors. Follow-up magnetic resonance imaging and positron emission tomography did not reveal tumor recurrence for 18 months. CONCLUSIONS: As far as we know, this is the first case of multiple craniospinal germinomas in a patient with DS who achieved a successful treatment result without fatal adverse events. The literature review indicated that disseminated germinomas may need intensive treatment to reduce recurrence risk. However, intensive chemotherapy using a combination of 3 or more anticancer drugs can increase the rate of treatment-related death during the early stage. Our case indicated that multiple craniospinal germinoma of DS patients could be treated with a standard dose of carboplatin and etoposide regimen with concurrent craniospinal irradiation along with appropriate supportive therapy and careful observation.

TÍTULO / TITLE:    - Protocol study for a randomised, controlled, double-blind, clinical trial involving virtual reality and anodal transcranial direct current stimulation for the improvement of upper limb motor function

REVISTA / JOURNAL:    - British Medical J (BMJ). Bibliographic Citation British Medical J. (BMJ): <> Open. 2017 Aug 11;7(8):

Enlace a la Editora de la Revista http://bmj.com/search.dtl

AUTORES / AUTHORS: - Lopes JBP; et al.

INSTITUCIÓN / INSTITUTION: - Doctoral and Master Programs in Rehabilitation Sciences, Movement Analysis Lab, University Nove de Julho, Sao Paulo, Brazil.  

RESUMEN / SUMMARY: - Down syndrome results in neuromotor impairment that affects selective motor control, compromising the acquisition of motor skills and functional independence. The aim of the proposed study is to evaluate and compare the effects of multiple-monopolar anodal transcranial direct current stimulation and sham stimulation over the primary motor cortex during upper limb motor training involving virtual reality on motor control, muscle activity, cerebral activity and functional independence. METHODS AND ANALYSIS: A randomised, controlled, double-blind, clinical trial is proposed. The calculation of the sample size will be defined based on the results of a pilot study involving the same methods. The participants will be randomly allocated to two groups. Evaluations will be conducted before and after the intervention as well as 1 month after the end of the intervention process. At each evaluation, three-dimensional analysis of upper limb movement muscle activity will be measured using electromyography, cerebral activity will be measured using an electroencephalogram system and intellectual capacity will be assessed using the Wechsler Intelligence Scale for Children. Virtual reality training will be performed three times a week (one 20 min session per day) for a total of 10 sessions. During the protocol, transcranial stimulation will be administered concomitantly to upper limb motor training. The results will be analysed statistically, with a p value ORTHOPEDICS - ORTOPEDÍA

TÍTULO / TITLE:    - Foot Structure in Boys with Down Syndrome.

REVISTA / JOURNAL:    - Biomed Res Int. 2017;2017:7047468. doi: 10.1155/2017/7047468. Epub 2017 Aug 21.

Enlace a la Editora de la Revista http://dx.doi.org/10.1155/2017/7047468

AUTORES / AUTHORS: - Puszczalowska-Lizis E; Nowak K;

INSTITUCIÓN / INSTITUTION: - Special Purpose School and Education Center, Mrowla 79C, 36-054 Mrowla, Poland.  

RESUMEN / SUMMARY: - INTRODUCTION AND AIM: Down syndrome (DS) is associated with numerous developmental abnormalities, some of which cause dysfunctions of the posture and the locomotor system. The analysis of selected features of the foot structure in boys with DS versus their peers without developmental disorders is done. MATERIALS AND METHODS: The podoscopic examination was performed on 30 boys with DS aged 14-15 years. A control group consisted of 30 age- and gender-matched peers without DS. RESULTS: The feet of boys with DS are flatter compared to their healthy peers. The hallux valgus angle is not the most important feature differentiating the shape of the foot in the boys with DS and their healthy peers. In terms of the V toe setting, healthy boys had poorer results. CONCLUSIONS: Specialized therapeutic treatment in individuals with DS should involve exercises to increase the muscle strength around the foot joints, enhancing the stabilization in the joints and proprioception. Introducing orthotics and proper footwear is also important. It is also necessary to monitor the state of the foot in order to modify undertaken therapies.

PHYSIOTHERAPY - FISIOTERAPIA

TÍTULO / TITLE:    - Do adults with Down syndrome do the same amount of physical activity as adults without disability? A proof of principle study.

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2017 Sep 27. doi: 10.1111/jar.12416.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12416

AUTORES / AUTHORS: - Shields N et al.

INSTITUCIÓN / INSTITUTION: - School of Allied Health, La Trobe University, Bundoora, Vic., Australia.  

RESUMEN / SUMMARY: - This study compared levels of physical activity completed by adults with and without Down syndrome. METHOD: Fifteen adults with and 15 adults without Down syndrome matched for age and gender, took part. The intensity and duration of physical activity were measured using RT3 accelerometers worn for seven days. RESULTS: Only, 12 participants with Down syndrome had complete physical activity data, and these participants and their matched controls (total: six females, 18 males; aged 25.8 +/- 9.7) were included in the analyses. There were significantly lower levels of moderate and vigorous physical activity per day for people with Down syndrome (median = 27 min) compared to those without (median = 101 min) (p < .001). Participants without disability were twice more likely to achieve recommended levels of physical activity than people with Down syndrome. CONCLUSIONS: Adults with Down syndrome appear to participate in lower levels of physical activity than adults without Down syndrome. Further research should validate these estimates.

TÍTULO / TITLE:    - A comparison of the function, activity and participation and quality of life between down syndrome children and typically developing children.

REVISTA / JOURNAL:    - J Phys Ther Sci. 2017 Aug;29(8):1377-1380. doi: 10.1589/jpts.29.1377. Epub 2017 Aug 10.

Enlace a la Editora de la Revista http://dx.doi.org/10.1589/jpts.29.1377

AUTORES / AUTHORS: - Graduate School of Physical Therapy, Sahmyook University, Republic of Korea.

INSTITUCIÓN / INSTITUTION: - Graduate School of Physical Therapy, Sahmyook University, Republic of Korea  

RESUMEN / SUMMARY: - To compare function, activity, participation, and quality of life of Down syndrome children and typically developing children according to age. [Subjects and Methods] A total of 16 Down syndrome children and 20 children with typical development were included as subjects for this study. International Classification of Functioning, Disability, and Health (ICF) Child and Youth version (CY) developed by the World Health Organization (WHO) and a questionnaire were used to measure children’s functioning, activity, and participation. To measure quality of life, KIDSCREEN 52-HRQOL questionnaire was used in this study. [Results] ICF-CY function, activity, participation, and quality of life showed statistically significant differences between Down syndrome children and typically developing children. Down syndrome children with higher functions showed higher activities and participation. Higher function, activity and participation features were correlated with better quality of life. Higher function resulted in better quality of life. [Conclusion] Function, activity, participation, quality of life, and several common factors of Down syndrome children depend on the ability of children. Function of Down syndrome children affects their activity, participation, and quality of life. Activities and participations also affect quality of life. Therefore, children’s functional aspect is the foundation for quality of life.

TÍTULO / TITLE:    - Prediction of energy expenditure during walking in adults with down syndrome.

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2017 Aug 16. doi: 10.1111/jar.12392.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12392

AUTORES / AUTHORS: - Agiovlasitis S; Fernhall B;

INSTITUCIÓN / INSTITUTION: - Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA.  

RESUMEN / SUMMARY: - When developing walking programmes for improving health in adults with Down syndrome (DS), physical activity professionals are in need of an equation for predicting energy expenditure. We therefore developed and cross-validated an equation for predicting the rate of oxygen uptake (VO2 ; an index of energy expenditure) for adults with and without DS. METHOD: A total of 469 VO2 observations during walking across different speeds were available from 54 adults with DS and 61 adults without DS. RESULTS: Significant predictors of VO2 were speed, speed square, group and group-by-speed interaction. Separate models for each group showed that speed and its square significantly predicted VO2 . Absolute per cent error was small and did not differ between groups. CONCLUSION: Adults with DS have different VO2 response to walking speed from persons without DS. VO2 is predicted from speed with acceptable accuracy for persons with DS.

TÍTULO / TITLE:    - Pupil response and attention skills in Down syndrome.

REVISTA / JOURNAL:    - Res Dev Disabil. 2017 Nov;70:40-49. doi: 10.1016/j.ridd.2017.08.011. Epub 2017 Sep 6.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2017.08.011

AUTORES / AUTHORS: - Angulo-Chavira AQ; Arias-Trejo N;

INSTITUCIÓN / INSTITUTION: - Laboratorio de Psicolinguistica, Facultad de Psicologia, Universidad Nacional Autonoma de Mexico, Mexico   nariast@unam.mx

RESUMEN / SUMMARY: - Down syndrome (DS) is characterized by attentional problems. Little is known about the neural correlates of attention problems in DS due to difficulties in evaluation. Pupil dilation, associated with an increase in cognitive load and locus coeruleus-noradrenaline system activity in humans, is a neurophysiological measurement that may help to characterize such problems. The aim of this research was to investigate the link between a phasic pupil dilation response and target detection in people with DS, as compared with a control group with typical development (TD) matched by mental age. Participants performed an “oddball” task by means of an eye-tracker and a series of neuropsychological tests. Although the DS and control group demonstrated similar attentional skills and behavioral performance, the participants with DS showed greater pupil dilation. This result suggests that people with DS expend extra cognitive effort to achieve performance similar to those with TD. This finding is discussed in light of the attentional process in DS and the reliability of pupil dilation measurement in the study of attention and other cognitive processes in DS.

TÍTULO / TITLE:    - Psychological Support for Young Adults with Down Syndrome: Dohsa-Hou Program for Maladaptive Behaviors and Internalizing Problems.

REVISTA / JOURNAL:    - Front Psychol. 2017 Sep 1;8:1504. doi: 10.3389/fpsyg.2017.01504. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.3389/fpsyg.2017.01504

AUTORES / AUTHORS: - Fujino H;

INSTITUCIÓN / INSTITUTION: - Department of Special Needs Education, Oita UniversityOita, Japan.;  

RESUMEN / SUMMARY: - Psychological and psychiatric dysfunction is a major problem in a substantial proportion of young adults with Down syndrome. Some patients develop psychiatric issues, such as depressive, obsessive-compulsive, or psychotic-like disorders, in their late adolescence or young adulthood. Furthermore, these individuals may experience moderate to severe emotional and psychological distress. Development of a psychosocial treatment to address these issues is needed in addition to psychotropic medication. The current study reports two cases of young adults with Down syndrome, who presented psychiatric symptoms and marked disruption in their daily lives. These individuals participated in a Dohsa-hou treatment program. Following treatment, adaptive levels, maladaptive behaviors, and internalizing problems were evaluated by the Vineland Adaptive Behavior Scales-II. Participants showed improvement in maladaptive behaviors and internalizing problems; however, improvement in these areas may be influenced by baseline severity of the problems. This case report suggests that Dohsa-hou could be an effective therapeutic approach for maladaptive and internalizing problems in adults with Down syndrome.

PRENATAL DIAGNOSIS - DIAGNÓSTICO

TÍTULO / TITLE:    - Down syndrome maternal serum markers in oocyte donation and other assisted reproductive technologies.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 Sep 16. doi: 10.1002/pd.5157.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5157

AUTORES / AUTHORS: - Bonnin A et al

INSTITUCIÓN / INSTITUTION: - Biochimie-Hormonologie, Hopital Robert Debre, AP-HP, 75019, Paris, France.  

RESUMEN / SUMMARY: - Because maternal serum markers (PAPP-A, hCGbeta, and AFP) used for Down syndrome (DS) screening have been described as predictors of obstetrical complications and because assisted reproductive technology (ART) pregnancies are known to be at increased risk for obstetrical complications, it is unclear whether or not correction factors should be applied to the calculated risk of DS. The purpose of this study was to evaluate DS maternal serum markers in oocyte donation (OD) and ART pregnancies in comparison with natural pregnancies. METHOD: Multicenter retrospective 2010-2013 study, in singleton pregnancies. Comparison of first- and second-trimester DS screening in 614 OD and 1921 ART pregnancies, versus 7268 natural pregnancies. RESULTS: There was a significant increase in hCGbeta in the OD group for both trimesters (first trimester: 1.28 MoM vs 1.02; p< 0.001 and second trimester: 1.32 MoM vs 1 MoM; p <0.001). PAPP-A was significantly lower in the ART group (0.92 and 1.02 MoM p <0.001). CONCLUSION: Maternal serum markers for DS screening are significantly modified in ART and OD pregnancies. Because these markers are also markers for obstetrical complications, the rationale for applying correction factors is questionable.

TÍTULO / TITLE:    - Measuring maternal serum screening markers for Down’s syndrome in plasma collected for cell-free DNA testing.

REVISTA / JOURNAL:    - J Med Screen. 2017 Sep;24(3):113-119. doi: 10.1177/0969141316670193. Epub 2016 Oct 21.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0969141316670193

AUTORES / AUTHORS: - Lambert-Messerlian GM; et al

INSTITUCIÓN / INSTITUTION: - 1 Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Providence, RI, USA.;   2 Department of Pathology and Laboratory Medicine, Alpert Medical School, Brown University, Providence, RI, USA.

RESUMEN / SUMMARY: - bjectives To determine whether maternal plasma collected in cell-free DNA stabilizing tubes is suitable for measuring prenatal screening ‘serum’ markers. Methods Matched plasma and serum samples were collected from 41 second trimester and 42 first trimester non-Down’s syndrome pregnancies. Second trimester samples were tested for alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A (Beckman Coulter DxI immunoassay). First trimester samples were tested for human chorionic gonadotropin and pregnancy-associated plasma protein A. Method comparisons performed for each marker compared plasma and serum results. Down’s syndrome likelihood ratios in serum and plasma were compared. Results Plasma and serum results for all markers were highly correlated ( r> 0.983) but for all, plasma results differed, usually by proportional amounts. After conversion to multiples of the median using sample type-specific medians, the logarithmic standard deviations in serum and plasma did not differ (all p > 0.37). Likelihood ratios for the first and second trimester marker combinations were highly correlated and closely agreed (log likelihood ratios range 1.005 to 1.032; 1.000 indicates complete agreement). Conclusions These results using specialized plasma collection tubes are similar to those of our earlier study showing that plasma collected in EDTA tubes is suitable for ‘serum’ Down’s syndrome screening. Laboratories must account for proportional changes by computing new plasma medians or modifying existing serum medians. Using a portion of the plasma from cell-free DNA collection tubes for ‘serum screening’ may have an advantage in programmes that are reflexively testing cell-free DNA, as only one sample type need be collected.

TÍTULO / TITLE:    - Cell-free fetal DNA analysis in maternal plasma as a screening test for trisomy 21, 18 and 13 in twin pregnancies.

REVISTA / JOURNAL:    - Ultrasound Obstet Gynecol. 2017 Aug 18. doi: 10.1002/uog.18838.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/uog.18838

AUTORES / AUTHORS: - Le Conte G; et al

INSTITUCIÓN / INSTITUTION: - Service de Gynecologie-Obstetrique et Medecine de la Reproduction, Hopital Antoine Beclere, Assistance Publique-Hopitaux de Paris, Clamart, France.;  

RESUMEN / SUMMARY: - To evaluate the utility of noninvasive prenatal testing using cell-free circulating fetal DNA (cfDNA) in screening for the three main autosomal fetal trisomies in twin pregnancies. METHODS: CfDNA testing was offered to 492 patients with twin pregnancies without ultrasound anomalies as a first-line screening test or after serum screening in clinical practice. Data were collected prospectively and a retrospective analysis was performed. CfDNA analysis was performed by massively parallel sequencing. The fetal fraction threshold for test evaluation was 8%. Regression analysis was performed to investigate the effect on the test failure rate of various variables. Performance of the test is also reported. RESULTS: The test was performed first line (after first-trimester scan) in 377 patients and following serum screening in 115. 78.8% of pregnancies were dichorionic-diamniotic. The test failed at the first attempt in 12 (2.9%) of 420 pregnancies with available outcomes, and regression analysis demonstrated that only maternal weight was a significant independent predictor of test failure. After redraw, a result was achieved in 10 cases. CfDNA identified all 3 cases of trisomy 21, and the only case of trisomy 18. For trisomy 21, the specificity was 99.8% (95% CI [98.7% - 100.0%]). When considering the spontaneous or ART origin of pregnancies, there were no significant differences in terms of maternal weight or of no-result rate for cfDNA screening in the two groups. CONCLUSIONS: In twin pregnancies without fetal ultrasound abnormalities, cfDNA had a high success rate and performance. Therefore, in routine practice, cfDNA could be considered as a first- or second-line screening test.

TÍTULO / TITLE:    - Ethnicity and Language Proficiency Differences in the Provision of and Intention to Use Prenatal Screening for Down’s Syndrome and Congenital Anomalies. A Prospective, Non-selected, Register-Based Stu

REVISTA / JOURNAL:    - Matern Child Health J. 2017 Sep 7. doi: 10.1007/s10995-017-2364-2.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10995-017-2364-2

AUTORES / AUTHORS: - Peters IA; et al.

INSTITUCIÓN / INSTITUTION: - Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Wytemaweg 80, Na-1515, 3015 GE, 3000 CA, Rotterdam, The Netherlands.   i.a.peters@erasmusmc.n

RESUMEN / SUMMARY: - Objective We aimed to conduct an analysis of the associations between the information provision procedure of prenatal screening for Down’s syndrome and congenital anomalies and the intention to participate in prenatal screening (PS) of ethnicity groups and Dutch language proficiency groups. Design Using a prospective web-based registration form, we asked counselors (midwives, general practitioners, nurses and gynecologists) to report whether and how they offered information about PS to pregnant women. Duration The study was conducted from 2008 to 2010. Participants We collected data on the characteristics of the women who received an information offer about PS from counselors. Measurements Measures included socio-demographic and language proficiency level (LPL) characteristics, key elements of the provision procedure of PS, and intentional participation in PS. Findings The dataset represents 37% of the total population in the study area. Women with a non-native Dutch background and/or insufficient Dutch LPL received fewer information offers about PS, faced a reduced chance of receiving counseling, and showed lower intentional participation rates for PS. Key Conclusions Women with a non-native Dutch background and/or with an insufficient LPL are underserved in the Dutch PS program. These findings present evidence indicating that the fundamental principle of the Dutch Population Screening Act, namely, equal access to PS for all pregnant women, is not being realized. Implications for Practice Therefore, the study findings are important for national and international healthcare, policy makers and governmental professionals to allow ethnic and LPL-related differences in the provision and intentional uptake of PS.

TÍTULO / TITLE:    - Obstetric professionals’ perceptions of non-invasive prenatal testing for Down syndrome: clinical usefulness compared with existing tests and ethical implications.

REVISTA / JOURNAL:    - BMC Pregnancy Childbirth. 2017 Sep 5;17(1):285. doi: 10.1186/s12884-017-1474-6.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12884-017-1474-6

AUTORES / AUTHORS: - Ngan OMY; et al

INSTITUCIÓN / INSTITUTION: - JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.;  

RESUMEN / SUMMARY: - While non-invasive prenatal testing (NIPT) for fetal aneuploidy is commercially available in many countries, little is known about how obstetric professionals in non-Western populations perceive the clinical usefulness of NIPT in comparison with existing first-trimester combined screening (FTS) for Down syndrome (DS) or invasive prenatal diagnosis (IPD), or perceptions of their ethical concerns arising from the use of NIPT. METHODS: A cross-sectional survey among 327 obstetric professionals (237 midwives, 90 obstetricians) in Hong Kong. RESULTS: Compared to FTS, NIPT was believed to: provide more psychological benefits and enable earlier consideration of termination of pregnancy. Compared to IPD, NIPT was believed to: provide less psychological stress for high-risk women and more psychological assurance for low-risk women, and offer an advantage to detect chromosomal abnormalities earlier. Significant differences in perceived clinical usefulness were found by profession and healthcare sector: (1) obstetricians reported more certain views towards the usefulness of NIPT than midwives and (2) professionals in the public sector perceived less usefulness of NIPT than the private sector. Beliefs about earlier detection of DS using NIPT were associated with ethical concerns about increasing abortion. Participants believing that NIPT provided psychological assurance among low-risk women were less likely to be concerned about ethical issues relating to informed decision-making and pre-test consultation for NIPT. CONCLUSIONS: Our findings suggest the need for political debate initially on how to ensure pregnant women accessing public services are informed about commercially available more advanced technology, but also on the potential implementation of NIPT within public services to improve access and equity to DS screening services.

QUALITY OF LIFE - CALIDAD DE VIDA

TÍTULO / TITLE:    - Hope, Coping, and Relationship Quality in Mothers of Children With Down Syndrome.

REVISTA / JOURNAL:    - J Marital Fam Ther. 2017 Aug 2. doi: 10.1111/jmft.12249.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jmft.12249

AUTORES / AUTHORS: - Cless JD; et al

INSTITUCIÓN / INSTITUTION: - Kansas State University.  

RESUMEN / SUMMARY: - Parenting a child with Down syndrome may pose unique challenges for parents’ relationship quality. This study used structural equation modeling with a sample of 351 mothers of children with Down syndrome to test if hope mediated the association between mothers’ various coping behaviors and mothers’ relationship quality. Hope was defined as a generalized positive state that comes from a personal sense of agency. Results indicated a greater degree of religious coping and internal coping were each significantly associated with more hope, whereas support seeking was not related with more hope. Higher hope was significantly associated with greater relationship quality. Bootstrapped indirect effects from both religious coping and internal coping to hope, and then hope to relationship quality, were identified. Implications for therapists and future research are described.

TÍTULO / TITLE:    - Health-Related Quality of Life in Individuals with Down Syndrome: Results from a Non-Interventional Longitudinal Multi-National Study.

REVISTA / JOURNAL:    - Adv Ther. 2017 Aug 9. doi: 10.1007/s12325-017-0591-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s12325-017-0591-y

AUTORES / AUTHORS: - Rofail D et al D’Ardhuy XL;

INSTITUCIÓN / INSTITUTION: - Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.  

RESUMEN / SUMMARY: - To date, there is little research on health-related quality of life (HRQoL) in Down syndrome (DS), and existing research is variable with regard to reported HRQoL in DS. There are also no HRQoL measures developed specifically to be used with individuals with Down syndrome. METHODS: A multi-national, longitudinal, 24-week non-interventional study was conducted in adolescents and adults with DS. HRQoL was assessed (n = 90) using the parent-report KIDSCREEN-27 questionnaire. RESULTS: HRQoL domain scores were found to be similar to those in the KIDSCREEN-27 European normative group data set on the Physical Well-being, Psychological Well-being, Autonomy and Parent Relations domains. Compared with the normative data set, the adolescent participants with DS in the current study were found to have lower scores on the Social Support and Peers domain and higher scores than the normative group on the School Environment domain. The test-retest reliability of the KIDSCREEN-27 was also examined using the intraclass correlation coefficient (ICC) in a subgroup of stable participants. The KIDSCREEN-27 demonstrated poor-to-moderate test-retest reliability; however, test-retest reliability was assessed using a long time interval between assessment time points. CONCLUSION: The findings of this study underline that further research is needed to better understand the nature of HRQoL in DS. Further research using a shorter time interval between assessment time points to examine test-retest reliability is also required. FUNDING: F. Hoffmann-La Roche Ltd.

TÍTULO / TITLE:    - Family members and health professionals’ perspectives on future life planning of ageing people with Down syndrome: a qualitative study.

REVISTA / JOURNAL:    - Disabil Rehabil. 2017 Aug 8:1-8. doi: 10.1080/09638288.2017.1362595.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/09638288.2017.1362595

AUTORES / AUTHORS: - Covelli V; Leonardi M; et al

INSTITUCIÓN / INSTITUTION: - b Neurology, Public Health and Disability Unit - Scientific Directorate , Neurological Institute C. Besta IRCCS Foundation , Milan , Italy.  

RESUMEN / SUMMARY: - To address the way in which primary caregivers of people over 45 with Down syndrome describe daily life activities and context and foresee their future. METHODS: Thirteen family members and 15 health professionals participated to four focus groups. Meaningful concepts were identified and linked to the International Classification of Functioning, Disability and Health using established linking rules. RESULTS: A total of 258 relevant concepts were identified and linked to 75 categories of the classification: 38 were from activity and participation and 17 from environmental factors domains. The most commonly reported issues were mental functions (b117-intellectual functions and b152-emotional functions), community life activities (d910-community life and d920-recreation and leisure) and environmental factors (e310-support of immediate family, e355-support from health professionals and e555-associations and organizational services). CONCLUSIONS: Information on the daily life and health of ageing people with Down syndrome is important to plan social and health care interventions tailored to deal with problems that they may encounter in older age. Considering the interaction between health and environment and maintaining a continuity of daily routines were reported as the most relevant topics for managing daily lives of persons with Down syndrome in older ages. Implications for rehabilitation Pay more attention to the interaction between environmental factors and health condition in ageing people with Down syndrome. Information about the life contest are important in order to plan present and future social-health care interventions. Future planning for people with Down syndrome is a great concern for family members.

TÍTULO / TITLE:    - Lifestyle factors and Alzheimer’s disease in people with Down syndrome.

REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2017 Jul 30. doi: 10.1111/jar.12369.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12369

AUTORES / AUTHORS: - Kenshole AV et al.

INSTITUCIÓN / INSTITUTION: - Livewell Southwest CIC, Plymouth, UK.  

RESUMEN / SUMMARY: - Lifestyle has previously been associated with the onset of Alzheimer’s disease (AD) in the typically developing population, but research investigating this association in Down syndrome (DS) is limited. METHOD: Adults with DS and AD (n = 27) were compared to adults with DS without AD (n = 30) on physical activity, diet, weight, where participants currently lived, where participants had lived for the majority of their lives, educational attainment, occupational attainment and cognitive activity. RESULTS: There was a significant difference between samples on where participants currently lived, with the majority of the clinical sample living in institutionalized settings and the majority of the control sample living in independent/supported living settings. This may reflect a tendency to move people once they start to deteriorate which, if correct, is contrary to clinical recommendations that people with AD should be supported to “die in place.” CONCLUSIONS: Further research into the way in which lifestyle factors, particularly living environment, could contribute to the increased risk of AD in adults with DS is required. This may support interventions aimed at preventing or delaying the onset of the disease.

TÍTULO / TITLE:    - A comparison of the function, activity and participation and quality of life between down syndrome children and typically developing children.

REVISTA / JOURNAL:    - J Phys Ther Sci. 2017 Aug;29(8):1377-1380. doi: 10.1589/jpts.29.1377. Epub 2017 Aug 10.

Enlace a la Editora de la Revista http://dx.doi.org/10.1589/jpts.29.1377

AUTORES / AUTHORS: - Jung HK; et al.

INSTITUCIÓN / INSTITUTION: - Graduate School of Physical Therapy, Sahmyook University, Republic of Korea.  

RESUMEN / SUMMARY: - To compare function, activity, participation, and quality of life of Down syndrome children and typically developing children according to age. [Subjects and Methods] A total of 16 Down syndrome children and 20 children with typical development were included as subjects for this study. International Classification of Functioning, Disability, and Health (ICF) Child and Youth version (CY) developed by the World Health Organization (WHO) and a questionnaire were used to measure children’s functioning, activity, and participation. To measure quality of life, KIDSCREEN 52-HRQOL questionnaire was used in this study. [Results] ICF-CY function, activity, participation, and quality of life showed statistically significant differences between Down syndrome children and typically developing children. Down syndrome children with higher functions showed higher activities and participation. Higher function, activity and participation features were correlated with better quality of life. Higher function resulted in better quality of life. [Conclusion] Function, activity, participation, quality of life, and several common factors of Down syndrome children depend on the ability of children. Function of Down syndrome children affects their activity, participation, and quality of life. Activities and participations also affect quality of life. Therefore, children’s functional aspect is the foundation for quality of life.

RESPIRATORY - RESPIRATORIO

TÍTULO / TITLE:    - The facial morphology in Down syndrome: A 3D comparison of patients with and without obstructive sleep apnea.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Aug 17. doi: 10.1002/ajmg.a.38399.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38399

AUTORES / AUTHORS: - Jayaratne YSN et al. Skotko B

INSTITUCIÓN / INSTITUTION: - Down Syndrome Program, Division of Developmental Medicine, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts. SUMMARY: Obstructive sleep apnea (OSA) occ  

RESUMEN / SUMMARY: - Obstructive sleep apnea (OSA) occurs at a high prevalence in patients with Down syndrome (DS). A polysomnogram, which is often cumbersome and challenging, remains the gold standard method of diagnosing OSA. OSA in patients with DS is often attributed to skeletal and soft-tissue structural alterations that are characteristic of the DS phenotype; as such, we hypothesized that assessing anthropometric facial measurements may be predictive of OSA in patients with DS. We used the 3dMDface sterophotography system to capture and create 3D facial images, and we subsequently identified facial landmarks using a single, experienced investigator and utilizing proprietary software to calculate inter-landmark distances and angles. We compared our findings with similar data for neurotypically developing participants. We further compared the findings in participants with DS with and without OSA. Participants with DS had maxillomandibular hypoplasia with smaller ear, nose, and eye measurements compared to neurotypically developing peers. We found no statistically significant differences in 3D photogrammetric measurements between participants with DS with or without OSA.

TÍTULO / TITLE:    - Accuracy of Parental Perception of Nighttime Breathing in Children with Down Syndrome.

REVISTA / JOURNAL:    - Otolaryngol Head Neck Surg. 2017 Sep 1:194599817726286. doi: 10.1177/0194599817726286.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0194599817726286

AUTORES / AUTHORS: - Friedman NR; et al

INSTITUCIÓN / INSTITUTION: - 1 Department of Pediatric Otolaryngology, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, USA.  

RESUMEN / SUMMARY: - Objective In 2011, the American Academy of Pediatrics published a guideline for children with Down syndrome (DS), recommending a polysomnogram (PSG) by age 4 years regardless of symptoms. Their rationale was based on 2 publications with small cohorts, where at least 50% of the children had no obstructive sleep apnea (OSA) symptoms but their PSG results were abnormal. The American Academy of Otolaryngology-Head and Neck Surgery Foundation published a clinical practice guideline recommending PSG prior to adenotonsillectomy for these children. This study aimed to assess parents’ accuracy of their children’s breathing patterns as compared with PSGs in a larger cohort of children with DS. Study Design Case series with chart review. Setting Tertiary care academic pediatric hospital. Subjects and Methods Sleep intake forms assessing frequency of parent-observed apnea, snoring, and restless sleep were analyzed. None of the children had a previous tonsillectomy. Two groups were analyzed according to symptoms: infrequent (<3 nights per week on all questions answered) and frequent (>/=6 nights per week on at least 1 question). OSA severity was categorized as follows: normal, <2 events per hour; mild, 2 to 4.9; moderate, 5 to 9.9; and severe,> /=10. Results A total of 113 children met inclusion criteria: 34% (n = 38) had infrequent symptoms, and 66% (n = 75) had frequent symptoms. Parents were unable to predict the presence or absence of OSA by nighttime symptoms ( P = .60). The risk of OSA for children with frequent symptoms versus those with infrequent symptoms was 1.04 (95% CI, 0.89-1.3). Conclusion Parents of DS children are unable to predict the presence or absence of OSA by nighttime symptoms, nor are they able to determine its severity.

TÍTULO / TITLE:    - Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

REVISTA / JOURNAL:    - Paediatr Drugs. 2017 Sep 11. doi: 10.1007/s40272-017-0264-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s40272-017-0264-y

AUTORES / AUTHORS: - Kashiwagi T; Nomoto K;

INSTITUCIÓN / INSTITUTION: - AbbVie GK, Mita 3-5-27, Minato-ku, Tokyo, 108-6302, Japan.   ken.nomoto@abbvie.com

RESUMEN / SUMMARY: - The aim of this study was to assess the safety and effectiveness of palivizumab for the prevention of lower respiratory tract infection (LRI) caused by respiratory syncytial virus (RSV) in children with immunocompromised conditions or Down syndrome. METHODS: In this multicenter, post-marketing surveillance study (December 2013 to December 2015), children aged 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;8(33):55760-55765. doi: 10.18632/oncotarget.17406. eCollection 2017 Aug 15.

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:    - Fetal pleural effusion and Down syndrome.

REVISTA / JOURNAL:    - Intractable Rare Dis Res. 2017 Aug;6(3):158-162. doi: 10.5582/irdr.2017.01028.

Enlace a la Editora de la Revista http://dx.doi.org/10.5582/irdr.2017.01028

AUTORES / AUTHORS: - Cao L; et al.

INSTITUCIÓN / INSTITUTION: - Ultrasound Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.  

RESUMEN / SUMMARY: - Fetal pleural effusion is a rare abnormality that results from accumulation of fluid in the chest cavity. It can be classified as primary fetal hydrothorax and secondary fetal hydrothorax. The underlying causes of pleural effusion are still unknown, and the current treatment strategies are mainly based on symptoms. The prognosis of fetal pleural effusion varies significantly, ranging from spontaneous resolution to perinatal death. Recent advances in prenatal diagnostic methods and treatment such as thoracoamniotic shunting have significantly improved the survival rates for patients with or without hydrops.

SURGERY - CIRUGÍA

TÍTULO / TITLE:    - Current Surgical Outcomes of Congenital Heart Surgery for Patients With Down Syndrome in Japan.

REVISTA / JOURNAL:    - Circ J. 2017 Sep 12. doi: 10.1253/circj.CJ-17-0483.

Enlace a la Editora de la Revista http://dx.doi.org/10.1253/circj.CJ-17-0483

AUTORES / AUTHORS: - Hoashi T; et al

INSTITUCIÓN / INSTITUTION: - The Japan Cardiovascular Surgery Database Organization.  

RESUMEN / SUMMARY: - Current surgical outcomes of congenital heart surgery for patients with Down syndrome are unclear.Methods and Results:Of 29,087 operations between 2008 and 2012 registered in the Japan Congenital Cardiovascular Surgery Database (JCCVSD), 2,651 were carried out for patients with Down syndrome (9%). Of those, 5 major biventricular repair procedures [ventricular septal defect repair (n=752), atrioventricular septal defect repair (n=452), patent ductus arteriosus closure (n=184), atrial septal defect repair (n=167), tetralogy of Fallot (TOF) repair (n=108)], as well as 2 major single ventricular palliations [bidirectional Glenn (n=21) and Fontan operation (n=25)] were selected and their outcomes were compared. The 90-day and in-hospital mortality rates for all 5 major biventricular repair procedures and bidirectional Glenn were similarly low in patients with Down syndrome compared with patients without Down syndrome. On the other hand, mortality after Fontan operation in patients with Down syndrome was significantly higher than in patients without Down syndrome (42/1,558=2.7% vs. 3/25=12.0%, P=0.005). CONCLUSIONS: Although intensive management of pulmonary hypertension is essential, analysis of the JCCVSD revealed favorable early prognostic outcomes after 5 major biventricular procedures and bidirectional Glenn in patients with Down syndrome. Indication of the Fontan operation for patients with Down syndrome should be carefully decided.

THERAPEUTICS - TERAPÉUTICA

TÍTULO / TITLE:    - Targeting trisomic treatments: optimizing Dyrk1a inhibition to improve Down syndrome deficits.

REVISTA / JOURNAL:    - Mol Genet Genomic Med. 2017 Sep 20;5(5):451-465. doi: 10.1002/mgg3.334. eCollection 2017 Sep.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/mgg3.334

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

INSTITUCIÓN / INSTITUTION: - Department of Psychology, IUPUI, 402 North Blackford Street, LD 124 Indianapolis , Indiana 46202-3275.   rjroper@iupui.edu

RESUMEN / SUMMARY: - Overexpression of Dual-specificity tyrosine-phosphorylated regulated kinase 1A (DYRK1A), located on human chromosome 21, may alter molecular processes linked to developmental deficits in Down syndrome (DS). Trisomic DYRK1A is a rational therapeutic target, and although reductions in Dyrk1a genetic dosage have shown improvements in trisomic mouse models, attempts to reduce Dyrk1a activity by pharmacological mechanisms and correct these DS-associated phenotypes have been largely unsuccessful. Epigallocatechin-3-gallate (EGCG) inhibits DYRK1A activity in vitro and this action has been postulated to account for improvement of some DS-associated phenotypes that have been reported in preclinical studies and clinical trials. However, the beneficial effects of EGCG are inconsistent and there is no direct evidence that any observed improvement actually occurs through Dyrk1a inhibition. Inconclusive outcomes likely reflect a lack of knowledge about the tissue-specific patterns of spatial and temporal overexpression and elevated activity of Dyrk1a that may contribute to emerging DS traits during development. Emerging evidence indicates that Dyrk1a expression varies over the life span in DS mouse models, yet preclinical therapeutic treatments targeting Dyrk1a have largely not considered these developmental changes. Therapies intended to improve DS phenotypes through normalizing trisomic Dyrk1a need to optimize the timing and dose of treatment to match the spatiotemporal patterning of excessive Dyrk1a activity in relevant tissues. This will require more precise identification of developmental periods of vulnerability to enduring adverse effects of elevated Dyrk1a, representing the concurrence of increased Dyrk1a expression together with hypothesized tissue-specific-sensitive periods when Dyrk1a regulates cellular processes that shape the long-term functional properties of the tissue. Future efforts targeting inhibition of trisomic Dyrk1a should identify these putative spatiotemp

TÍTULO / TITLE:    - Pharmacological interventions to improve cognition and adaptive functioning in Down syndrome: Strides to date.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Sep 8. doi: 10.1002/ajmg.a.38465.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38465

AUTORES / AUTHORS: - Hart SJ, et al. Liogier D’Ardhuy X;

INSTITUCIÓN / INSTITUTION: - F. Hoffmann-La Roche, Roche Pharma Research and Early Development, Neuroscience, Roche Innovation Center Basel, Basel, Switzerland.  

RESUMEN / SUMMARY: - Although an increasing number of clinical trials have been developed for cognition in Down syndrome, there has been limited success to date in identifying effective interventions. This review describes the progression from pre-clinical studies with mouse models to human clinical trials research using pharmacological interventions to improve cognition and adaptive functioning in Down syndrome. We also provide considerations for investigators when conducting human clinical trials and describe strategies for the pharmaceutical industry to advance the field in drug discovery for Down syndrome. Future research focusing on earlier pharmaceutical interventions, development of appropriate outcome measures, and greater collaboration between industry, academia, advocacy, and regulatory groups will be important for addressing limitations from prior studies and developing potential effective interventions for cognition in Down syndrome.

TÍTULO / TITLE:    - Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice.

REVISTA / JOURNAL:    - Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10268-10273. doi: 10.1073/pnas.1704143114. Epub 2017 S

Enlace a la Editora de la Revista http://dx.doi.org/10.1073/pnas.1704143114

AUTORES / AUTHORS: - Nakano-Kobayashi A; ... Hagiwara M

INSTITUCIÓN / INSTITUTION: - Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan   hagiwara.masatoshi.8c@kyoto-u.ac.jp

RESUMEN / SUMMARY: - Down syndrome (DS) caused by trisomy of chromosome 21 is the most common genetic cause of intellectual disability. Although the prenatal diagnosis of DS has become feasible, there are no therapies available for the rescue of DS-related neurocognitive impairment. A growth inducer newly identified in our screen of neural stem cells (NSCs) has potent inhibitory activity against dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and was found to rescue proliferative deficits in Ts65Dn-derived neurospheres and human NSCs derived from individuals with DS. The oral administration of this compound, named ALGERNON (altered generation of neurons), restored NSC proliferation in murine models of DS and increased the number of newborn neurons. Moreover, administration of ALGERNON to pregnant dams rescued aberrant cortical formation in DS mouse embryos and prevented the development of abnormal behaviors in DS offspring. These data suggest that the neurogenic phenotype of DS can be prevented by ALGERNON prenatal therapy.

TÍTULO / TITLE:    - Challenges in measuring the effects of pharmacological interventions on cognitive and adaptive functioning in individuals with Down syndrome: A systematic review.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Aug 31. doi: 10.1002/ajmg.a.38416.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38416

AUTORES / AUTHORS: - Keeling LA et al, Kishnani PS;

INSTITUCIÓN / INSTITUTION: - http://dx.doi.org/10.1002/ajmg.a.38416  

RESUMEN / SUMMARY: - We systematically reviewed the measures used in pharmaceutical trials in children/adults with Down syndrome without dementia. Our purpose was to identify developmentally appropriate outcome measures capable of detecting changes in cognitive and adaptive functioning in this population. Eleven studies were included and used diverse outcome measures across the domains of language, memory, attention, behavior, and executive/adaptive functioning. Our results highlight the challenges in selecting measures capable of capturing improvements in pharmaceutical trials in individuals with DS. We offer suggestions to enhance future research, including: conducting studies with larger samples of participants with a range of developmental abilities; modifying existing/developing novel outcome measures; incorporating advances from related areas and DS observational studies; and considering alternative analytic techniques to characterize treatment effects.

TÍTULO / TITLE:    - Mitochondria as pharmacological targets in Down syndrome.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Aug 31. pii: S0891-5849(17)30730-X. doi: 10.1016/j.freeradbiomed.2017.08.0

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.014

AUTORES / AUTHORS: - Valenti D; et al., Vacca RA;

INSTITUCIÓN / INSTITUTION: - Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy.   r.vacca@ibiom.cnr.it

RESUMEN / SUMMARY: - Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS. DS is associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, molecular mechanisms responsible for mitochondrial damage and energy deficits have been identified and characterized in several DS-derived human cells and animal models of DS. Therefore, therapeutic strategies targeting mitochondria could have great potential for new treatment regimens in DS. The purpose of this review is to highlight recent studies concerning mitochondrial impairment in DS, focusing on alterations of the molecular pathways controlling mitochondrial function. We will also discuss the effects and molecular mechanisms of naturally occurring and chemically synthetized drugs that exert neuroprotective effects through modulation of mitochondrial function and attenuation of oxidative stress. These compounds might represent novel therapeutic tools for the modulation of energy deficits in DS.

TÍTULO / TITLE:    - Protocol study for a randomised, controlled, double-blind, clinical trial involving virtual reality and anodal transcranial direct current stimulation for the improvement of upper limb motor function

REVISTA / JOURNAL:    - British Medical J (BMJ). Link to the complete text (free or ppv) 1136/bmjopen-2017-016260

Enlace a la Editora de la Revista http://bmj.com/search.dtl

AUTORES / AUTHORS: - Lopes JBP; et al.

INSTITUCIÓN / INSTITUTION: - Doctoral and Master Programs in Rehabilitation Sciences, Movement Analysis Lab, University Nove de Julho, Sao Paulo, Brazil.  

RESUMEN / SUMMARY: - Down syndrome results in neuromotor impairment that affects selective motor control, compromising the acquisition of motor skills and functional independence. The aim of the proposed study is to evaluate and compare the effects of multiple-monopolar anodal transcranial direct current stimulation and sham stimulation over the primary motor cortex during upper limb motor training involving virtual reality on motor control, muscle activity, cerebral activity and functional independence. METHODS AND ANALYSIS: A randomised, controlled, double-blind, clinical trial is proposed. The calculation of the sample size will be defined based on the results of a pilot study involving the same methods. The participants will be randomly allocated to two groups. Evaluations will be conducted before and after the intervention as well as 1 month after the end of the intervention process. At each evaluation, three-dimensional analysis of upper limb movement muscle activity will be measured using electromyography, cerebral activity will be measured using an electroencephalogram system and intellectual capacity will be assessed using the Wechsler Intelligence Scale for Children. Virtual reality training will be performed three times a week (one 20 min session per day) for a total of 10 sessions. During the protocol, transcranial stimulation will be administered concomitantly to upper limb motor training. The results will be analysed statistically, with a p value EDUCATION - EDUCACIÓN

TÍTULO / TITLE:    - Prolonged toilet training in children with Down syndrome: a case-control study.

REVISTA / JOURNAL:    - J Pediatr (Rio J). 2017 Sep 1. pii: S0021-7557(16)30430-2. doi: 10.1016/j.jped.2017.06.011.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jped.2017.06.011

AUTORES / AUTHORS: - Mrad FCC; et al

INSTITUCIÓN / INSTITUTION: - Universidade Federal de Juiz de Fora (UFJF), Departamento de Cirurgia, Nucleo Interdisciplinar de Pesquisa em Urologia (NIPU), Juiz de Fora, MG, Brazil; Universidade Federal de Minas Gerais (UFMG), Departamento de Pediatria, Belo Horizonte,   flaviamrad@terra.com.br

RESUMEN / SUMMARY: - OBJECTIVES: Children with Down syndrome have delayed psychomotor development, which is a factor that influences the level of difficulty in toilet training. The current study aims to estimate the age toilet training starts and completes in children with DS compared to children with normal psychomotor development and to evaluate the method and type of toilet training most frequently used, as well as its association with lower urinary tract symptoms and functional constipation. METHODS: A case-control study was carried out from 2010 to 2015. All parents completed a questionnaire designed to assess the toilet training process. Lower urinary tract symptoms were assessed through the application of the Dysfunctional Voiding Symptom Score. The presence of functional constipation was assessed according to the Rome III criteria. RESULTS: The study included 93 children with Down syndrome and 204 children with normal psychomotor development (control group [CG]). The mean age of toilet training onset was 22.8 months in those with DS and 17.5 months in the CG (p=0.001). In children with DS, the mean age when completing toilet training was 56.2 months and 27.1 months in the CG (p=0.001). Among children with DS, females completed toilet training earlier (p=0.02). The toilet training method used most often was child-oriented approach in both groups. No association was observed with the presence of lower urinary tract symptoms or functional constipation and the age of beginning and completing toilet training in both groups. CONCLUSION: Children with Down syndrome experienced prolonged toilet training time. Prospective longitudinal studies are essential to gain insight into the toilet training of these children.

TÍTULO / TITLE:    - Analyses of Sustained Vowels in Down Syndrome (DS): A Case Study Using Spectrograms and Perturbation Data to Investigate Voice Quality in Four Adults With DS.

REVISTA / JOURNAL:    - J Voice. 2017 Sep 21. pii: S0892-1997(17)30151-0. doi: 10.1016/j.jvoice.2017.08.004.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jvoice.2017.08.004

AUTORES / AUTHORS: - Jeffery T; et al

INSTITUCIÓN / INSTITUTION: - Bishop Grosseteste University, Lincoln, UK.   Tracy.jeffery@bishopg.ac.uk

RESUMEN / SUMMARY: - OBJECTIVES: Automatic acoustic measures of voice quality in people with Down syndrome (DS) do not reliably reflect perceived voice qualities. This study used acoustic data and visual spectral data to investigate the relationship between perceived voice qualities and acoustic measures. STUDY DESIGN: Participants were four young adults (two males, two females; mean age 23.8 years) with DS and severe learning disabilities, at least one of whom had a hearing impairment. METHODS: Participants imitated sustained /i/, /u/, and /a/ vowels at predetermined target pitches within their vocal range. Medial portions of vowels were analyzed, using Praat, for fundamental frequency, harmonics-to-noise ratio, jitter, and shimmer. Spectrograms were used to identify the presence and the duration of subharmonics at onset and offset, and mid-vowel. The presence of diplophonia was assessed by auditory evaluation. RESULTS: Perturbation data were highest for /a/ vowels and lowest for /u/ vowels. Intermittent productions of subharmonics were evident in spectrograms, some of which coincided with perceived diplophonia. The incidence, location, duration, and intensity of subharmonics differed between the four participants. CONCLUSIONS: Although the acoustic data do not clearly indicate atypical phonation, diplophonia and subharmonics reflect nonmodal phonation. The findings suggest that these may contribute to different perceived voice qualities in the study group and that these qualities may result from intermittent involvement of supraglottal structures. Further research is required to confirm the findings in the wider DS population, and to assess the relationships between voice quality, vowel type, and physiological measures.

TÍTULO / TITLE:    - Communication about emotions during storybook reading: Effects of an instruction programme for children with Down syndrome.

REVISTA / JOURNAL:    - Int J Speech Lang Pathol. 2017 Aug 7:1-11. doi: 10.1080/17549507.2017.1356376.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/17549507.2017.1356376

AUTORES / AUTHORS: - Na JY; Wilkinson KM;

INSTITUCIÓN / INSTITUTION: - b Department of Communication Sciences and Disorders , The Pennsylvania State University , State College , PA , USA.  

RESUMEN / SUMMARY: - Children with Down syndrome often have more restricted emotion expression and recognition skills than their peers who are developing typically, and potentially fewer opportunities to learn these skills. This study investigated the effect of the Strategies for Talking about Emotions as PartnerS (STEPS) programme on parents’ provision of opportunities for emotion communication using visual communication supports. METHOD: The study used a single-subject multiple-baseline across participants design with three parent-child dyads. Shared book reading was used as the context for parent instruction and data collection. RESULT: Parents increased their use of the emotion communication strategies immediately following an instructional session, and continued to use them for the remaining phases of the study. In turn, the children participated more actively in the discussion by making comments about emotions when parents provided more opportunities. CONCLUSION: The STEPS instructional programme is effective for improving parents’ provision of opportunities for discussing emotions during storybook reading with children who have Down syndrome. All parents indicated that they would use the strategy during future reading activities. This paper discusses the results of the study and directions for future research.

TÍTULO / TITLE:    - Acoustic parameters of infant-directed singing in mothers of infants with down syndrome.

REVISTA / JOURNAL:    - Infant Behav Dev. 2017 Sep 18;49:151-160. doi: 10.1016/j.infbeh.2017.09.001.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.infbeh.2017.09.001

AUTORES / AUTHORS: - de l’Etoile S; et al

INSTITUCIÓN / INSTITUTION: - University of Miami, Frost School of Music, United States.   sdel@miami.edu

RESUMEN / SUMMARY: - This study compared the acoustic parameters and degree of perceived warmth in two types of infant-directed (ID) songs - the lullaby and the playsong - between mothers of infants with Down syndrome (DS) and mothers of typically-developing (TD) infants. Participants included mothers of 15 DS infants and 15 TD infants between 3 and 9 months of age. Each mother’s singing voice was digitally recorded while singing to her infant and subjected to feature extraction and data mining. Mothers of DS infants and TD infants sang both lullabies and playsongs with similar frequency. In comparison with mothers of TD infants, mothers of DS infants used a higher maximum pitch and more key changes during playsong. Mothers of DS infants also took more time to establish a rhythmic structure in their singing. These differences suggest mothers are sensitive to the attentional and arousal needs of their DS infants. Mothers of TD infants sang with a higher degree of perceived warmth which does not agree with previous observations of “forceful warmth” in mothers of DS infants. In comparison with lullaby, all mothers sang playsong with higher overall pitch and slower tempo. Playsongs were also distinguished by higher levels of spectral centroid properties related to emotional expressivity, as well as higher degrees of perceived warmth. These similarities help to define specific song types, and suggest that all mothers sing in an expressive manner that can modulate infant arousal, including mothers of DS infants.
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