Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome.

International audienceBACKGROUND: Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene-dosage effects on language development at 7q11.23 have been hypothesized. METHODS: Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined. RESULTS: The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production. CONCLUSIONS: Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype-phenotype correlations, possible gene-environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism

Tracking Subtle Stereotypes of Children with Trisomy 21: From Facial-Feature-Based to Implicit Stereotyping

Background: Stigmatization is one of the greatest obstacles to the successful integration of people with Trisomy 21 (T21 or Down syndrome), the most frequent genetic disorder associated with intellectual disability. Research on attitudes and stereotypes toward these people still focuses on explicit measures subjected to social-desirability biases, and neglects how variability in facial stigmata influences attitudes and stereotyping. Methodology/Principal Findings: The participants were 165 adults including 55 young adult students, 55 non-student adults, and 55 professional caregivers working with intellectually disabled persons. They were faced with implicit association tests (IAT), a well-known technique whereby response latency is used to capture the relative strength with which some groups of people—here photographed faces of typically developing children and children with T21—are automatically (without conscious awareness) associated with positive versus negative attributes in memory. Each participant also rated the same photographed faces (consciously accessible evaluations). We provide the first evidence that the positive bias typically found in explicit judgments of children with T21 is smaller for those whose facial features are highly characteristic of this disorder, compared to their counterparts with less distinctive features and to typically developing children. We also show that this bias can coexist with negative evaluations at the implicit level (with large effect sizes), even among professional caregivers

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer’s disease

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer’s disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Law and Migration in a Changing World: General Report

This General Report draws from twenty-six national reports. Structured in two parts, it investigates the status of the migration law regimes in receiving countries, where migration events have come under intense domestic and international crutiny. The first part (Sects. 2–4) compares the legislative, judicial, and administrative instruments regulating foreign arrivals and stays, signaling an evolution towards a jus commune in the highly plural and interactive world of legal orders and sources, judicial and decision-making bodies, as well as hierarchies and sovereignties. The second part (Sects. 5–6) reflects on convergences and divergences, and how countries variously leverage such instruments to formulate their migration management policies. Although a given in the legal field, the gap, especially between law and practice, is frighteningly wide in migration matters, with dramatic consequences for some categories of migrants, their communities, and—directly and indirectly—for their countries of origin and the society where they seek a new life. The General Report advocates for the human rights of migrants to be more firmly imprinted in understandings of national sovereignty and security and a greater permeability of national law to international human rights law

Law and Migration in a Changing World

This volume comprises national reports on migration and migration law from 17 countries representing all continents. The vast majority of these are countries of immigration, which means they face specific challenges in terms of managing migratory flows that are increasingly linked with climate change and scarce natural resources worldwide, and they need to find viable ways to integrate humanitarian migration. Unlike so many recent publications in the field of international migration law, this book brings together reports on diverse countries that are rarely regarded as part of one and the same picture, depicting globalized migration in the contemporary era that to a large extent challenges state sovereignty. The contributions delineate the legal regimes that individual states are continually developing and modifying with a view to managing and controlling access of individual persons to their respective territories. They also show how the restrictive measures that states resort to in the event of failure to manage migration could have a lasting legal impact. The General Report preceding the country reports provides a comparative overview of the national reports, and is divided into two parts. The first, more technical in nature, addresses the classic questions relating to admission to and residence in a country. The second, more reflective section, examines the relationship between laws and migration in a wider and multidisciplinary perspective. To allow a robust comparison, the country reports all follow a similarly wide-ranging structure; to the extent possible, they also cover the historical, sociological and demographic factors that help explain legal regimes and migratory flows in each country. Each country report includes analyses of recent legislative developments and delicate questions that are still awaiting adequate (legal) responses as well as perspectives for the future

Estudio de costo/beneficio de un programa de control de Enfermedad de Chagas Congénita en Bolivia.

Cost effectiveness analysis of Chagas' vertical transmission control program in Bolivia: Today, Bolivia is the most concerned country in America by Chagas disease: Trypanosoma cruzi infection affects 20% of whole population, around 1800000 inhabitants, and mother-to-child transmission is around 5%, from 1.6 to 9.8%. Direct and indirect costs derived from disease complications and death, from birth to adulthood, add up around US$21 millions per year for 2,718 infected new-borns. This cost falls on individual, family and society, when the nation is struggling in a depressed economy. On the other side, an effective control program could detect and treat all cases with an investment of US$ 123 per infected new-born, or US$ 1.2 per new-born in Bolivia. Indirect benefits, apart of suffering relieve and improving of life quality, are related with Chagas vector control program, increasing the demand thanks to increasing risk awareness and also induced demand testing all pregnant women in endemic areas. So the conclusion is that such investment is profitable.English AbstractJournal Articleinfo:eu-repo/semantics/publishe