Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%–2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5′ region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10−11). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84–0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860–0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83–0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83–0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3•5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

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Bison (Bison bison) and elk (Cervus elaphus) of the Greater Yellowstone Area (GYA) are the last remaining reservoirs of bovine brucellosis (Brucella abortus) in the United States. An important factor in evaluating the risk of transmission to cattle is the persistence of bacteria and infectious birth materials shed on pastures where cattle graze. We selected 2 study areas near the northern and western boundaries of Yellowstone National Park (YNP) to determine the persistence of bacteria on fetal tissue, soil, and vegetation, and scavenging on infectious materials from birth and abortion sites. We performed 3 independent field experiments to determine: 1) persistence of Brucella abortus (RB51) purposely applied to fetal tissues, 2) scavenging of fetuses by native scavengers, and 3) natural contamination of birth or abortion sites in the GYA. Results from these field experiments established that Brucella bacteria can persist on fetal tissues and soil or vegetation for 21-81 days depending on month, temperature, and exposure to sunlight. Bacteria purposely applied to fetal tissues persisted longer in February than May and did not survive on tissues beyond 10 June regardless of when they were set out. Brucella abortus field strain persisted up to 43 days on soil and vegetation at naturally contaminated bison birth or abortion sites. Fetuses were scavenged by a variety of birds and mammals in areas near YNP and more rapidly inside YNP than outside the Park boundary. Models derived from our data determined a 0.05% chance of bacterial survival beyond 26 days (95% Credible Interval of 18-30 days) for a contamination event in May. May 15 is the final date for hazing all bison into Yellowstone National Park under the current interagency bison management plan. With these data managers can predict when it is safe to graze cattle onto pastures previously occupied by bison. ß 2011 The Wildlife Society.

PurposeTo comprehensively identify the determinants of quality of life (QoL) in a population study sample of persons aged 18–50 and 50+.MethodsIn this observational, cross-sectional study, QoL was measured with the WHOQOL-AGE, a brief instrument designed to measure QoL in older adults. Eight hierarchical regression models were performed to identify determinants of QoL. Variables were entered in the following order: Sociodemographic; Health Habits; Chronic Conditions; Health State description; Vision and Hearing; Social Networks; Built Environment. In the final model, significant variables were retained. The final model was re-run using data from the three countries separately.ResultsComplete data were available for 5639 participants, mean age 46.3 (SD 18.4). The final model accounted for 45% of QoL variation and the most relevant contribution was given by sociodemographic data (particularly age, education level and living in Finland: 17.9% explained QoL variation), chronic conditions (particularly depression: 4.6%) and a wide and rich social network (4.6%). Other determinants were presence of disabling pain, learning difficulties and visual problems, and living in usable house that is perceived as non-risky. Some variables were specifically associated to QoL in single countries: age in Poland, alcohol consumption in Spain, angina in Finland, depression in Spain, and self-reported sadness both in Finland and Poland, but not in Spain. Other were commonly associated to QoL: smoking status, bodily aches, being emotionally affected by health problems, good social network and home characteristics.ConclusionsOur results highlight the importance of modifiable determinants of QoL, and provide public health indications that could support concrete actions at country level. In particular, smoking cessation, increasing the level of physical activity, improving social network ties and applying universal design approach to houses and environmental infrastructures could potentially increase QoL of ageing population.

Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay. Microarray-based comparative genomic hybridization identified structural chromosomal alterations responsible for the intellectual disability/developmental delay phenotype in 16% of our sample. Our study showed that causative copy number variants are frequently found even in cases of mild intellectual disability (30.77%). We want to emphasize the need to conduct microarray-based comparative genomic hybridization on all individuals with intellectual disability/developmental delay, regardless of the severity, because the degree of intellectual disability/developmental delay does not predict the diagnostic yield of microarray-based comparative genomic hybridization.

Background: Specific cognitive rehabilitation in multiple sclerosis (MS) resulted to be effective compared to no treatment. So far the possible role of an aspecific psychological intervention on cognition has not been investigated.Objective: The aim of the SMICT RCT was to compare the efficacy of a specific cognitive training with an aspecific psychological intervention in relapsing-remitting MS patients.Methods: From a sample of 150 patients, with the same disability and immunomodulatory therapy, submitted to neuropsychological examination, 45 impaired in at least one test were included and 41 randomized to have either a specific cognitive training for the impaired function (22) or to an aspecific psychological intervention (19) for 4 months, starting after baseline examination. Neuropsychological tests and functional scales were administered at baseline and 1 year later.Results: After 1 year, the mean number of pathological tests was significantly lower in the specific treatment group, compared to the aspecific group. Memory and attention/speeded information processing functions were mostly improved. Depression and quality of life were not different between groups at follow up.Conclusion: Our study demonstrates that an intensive and domain specific cognitive approach results to be more effective than aspecific psychological intervention in patients with MS.

Background Attention-Deficit/ Hyperactivity Disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Symptoms related to this disorder cause a significant impairment in school tasks and in the activities of children’s daily lives; an early diagnosis and appropriate treatment could almost certainly help improve their outcomes. The current study, part of the Models Of Child Health Appraised (MOCHA) project, aims to explore the age at which children experience the onset or diagnosis of ADHD in European countries. Methods A systematic review was done examining the studies reporting the age of onset/diagnosis (AO/AD) of ADHD in European countries (28 European Member States plus 2 European Economic Area countries), published between January 1, 2010 and December 31, 2019. Of the 2276 identified studies, 44 met all the predefined criteria and were included in the review. Results The lowest mean AO in the children diagnosed with ADHD alone was 2.25 years and the highest was 7.5 years. It was 15.3 years in the children with ADHD and disruptive behaviour disorder. The mean AD ranges between 6.2 and 18.1 years. Conclusions Our findings indicate that there is a wide variability in both the AO and AD of ADHD, and a too large distance between AO and AD. Since studies in the literature suggest that an early identification of ADHD symptoms may facilitate early referral and treatment, it would be important to understand the underlying reasons behind the wide variability found. Trial registration PROSPERO registration: CRD42017070631.