Huntington's disease phenocopies are clinically and genetically heterogeneous

Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD-like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD-like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral-pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty-five patients with syndromes consistent with HD, who were HD expansion-negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. (c) 2008 Movement Disorder Society

Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19

OBJECTIVE: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents. METHOD: For this rapid review, we searched MEDLINE, PSYCHINFO, and Web of Science for articles published between 01/01/1946 and 03/29/2020. 20% of articles were double screened using pre-defined criteria and 20% of data was double extracted for quality assurance. RESULTS: 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n=51,576; mean age 15.3) 61 studies were observational; 18 were longitudinal and 43 cross sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time loneliness was measured and between 0.25 to 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness. CONCLUSION: Children and adolescents are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventative support and early intervention where possible and be prepared for an increase in mental health problems

Costs of TB services in India (No 1).

BACKGROUND: There is a dearth of economic analysis required to support increased investment in TB in India. This study estimates the costs of TB services from a health systems´ perspective to facilitate the efficient allocation of resources by India´s National Tuberculosis Elimination Programme.METHODS: Data were collected from a multi-stage, stratified random sample of 20 facilities delivering TB services in two purposively selected states in India as per Global Health Cost Consortium standards and using Value TB Data Collection Tool. Unit costs were estimated using the top-down (TD) and bottom-up (BU) methodology and are reported in 2018 US dollars.RESULTS: Cost of delivering 50 types of TB services and four interventions varied according to costing method. Key services included sputum smear microscopy, Xpert® MTB/RIF and X-ray with an average BU costs of respectively US$2.45, US$17.36 and US$2.85. Average BU cost for bacille Calmette-Guérin vaccination, passive case-finding, TB prevention in children under 5 years using isoniazid and first-line drug treatment in new pulmonary and extrapulmonary TB cases was respectively US$0.76, US$1.62, US$2.41, US$103 and US$98.CONCLUSION: The unit cost of TB services and outputs are now available to support investment decisions, as diagnosis algorithms are reviewed and prevention or treatment for TB are expanded or updated in India

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).

Optimal constraint-based decision tree induction from itemset lattices

International audienceIn this article we show that there is a strong connection between decision tree learning and local pattern mining. This connection allows us to solve the computationally hard problem of finding optimal decision trees in a wide range of applications by post-processing a set of patterns: we use local patterns to construct a global model. We exploit the connection between constraints in pattern mining and constraints in decision tree induction to develop a framework for categorizing decision tree mining constraints. This framework allows us to determine which model constraints can be pushed deeply into the pattern mining process, and allows us to improve the state-of-the-art of optimal decision tree induction

Widespread environmental contamination with Mycobacterium tuberculosis complex revealed by a molecular detection protocol

Environmental contamination with Mycobacterium tuberculosis complex (MTC) has been considered crucial for bovine tuberculosis persistence in multi-host-pathogen systems. However, MTC contamination has been difficult to detect due to methodological issues. In an attempt to overcome this limitation we developed an improved protocol for the detection of MTC DNA. MTC DNA concentration was estimated by the Most Probable Number (MPN) method. Making use of this protocol we showed that MTC contamination is widespread in different types of environmental samples from the Iberian Peninsula, which supports indirect transmission as a contributing mechanism for the maintenance of bovine tuberculosis in this multi-host-pathogen system. The proportion of MTC DNA positive samples was higher in the bovine tuberculosis-infected than in presumed negative area (0.32 and 0.18, respectively). Detection varied with the type of environmental sample and was more frequent in sediment from dams and less frequent in water also from dams (0.22 and 0.05, respectively). The proportion of MTC-positive samples was significantly higher in spring (p<0.001), but MTC DNA concentration per sample was higher in autumn and lower in summer. The average MTC DNA concentration in positive samples was 0.82 MPN/g (CI95 0.70-0.98 MPN/g). We were further able to amplify a DNA sequence specific of Mycobacterium bovis/caprae in 4 environmental samples from the bTB-infected area

Strategies for recruiting Hispanic women into a prospective cohort study of modifiable risk factors for gestational diabetes mellitus

BACKGROUND: The purpose of this article was to describe effective strategies for recruitment of Hispanic women into a prospective cohort study of modifiable risk factors for gestational diabetes mellitus (GDM). Although Hispanic women have two to four times the risk of developing GDM compared with non-Hispanic white women, few GDM prevention studies have included Hispanic women. METHODS: The study was conducted in the ambulatory obstetrical practices of Baystate Medical Center located in a socioeconomically and ethnically diverse city in Massachusetts. The study employed a range of strategies to recruit Hispanic women based on a review of the literature as well as prior experience with the study population. RESULTS: Over a period of 32 months, a total of 851 Hispanic prenatal care patients were recruited. Among eligible women, 52.4% agreed to participate. Participants were young (70% <25 years), with low levels of education, and on public health insurance (81.5%); 88% were unmarried. Study design features such as use of bilingual recruiters, a flexible recruitment process, training recruiters to be culturally sensitive, use of culturally tailored materials, prescreening participants, participant compensation, seeking the cooperation of clinic staff, and continuous monitoring of recruitment goals emerged as important issues influencing recruitment. CONCLUSIONS: Findings suggest that investigators can successfully recruit pregnant women from ethnic minority groups of low socioeconomic status into observational studies. The study provides culturally appropriate recruitment strategies useful for practice-based settings recruiting Hispanic research participation

Expression of the blood-group-related glycosyltransferase B4galnt2 influences the intestinal microbiota in mice

Glycans on mucosal surfaces have an important role in host–microbe interactions. The locus encoding the blood-group-related glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2) is subject to strong selective forces in natural house-mouse populations that contain a common allelic variant that confers loss of B4galnt2 gene expression in the gastrointestinal (GI) tract. We reasoned that altered glycan-dependent intestinal host–microbe interactions may underlie these signatures of selection. To determine whether B4galnt2 influences the intestinal microbial ecology, we profiled the microbiota of wild-type and B4galnt2-deficient siblings throughout the GI tract using 16S rRNA gene pyrosequencing. This revealed both distinct communities at different anatomic sites and significant changes in composition with respect to genotype, indicating a previously unappreciated role of B4galnt2 in host–microbial homeostasis. Among the numerous B4galnt2-dependent differences identified in the abundance of specific bacterial taxa, we unexpectedly detected a difference in the pathogenic genus, Helicobacter, suggesting Helicobacter spp. also interact with B4galnt2 glycans. In contrast to other glycosyltransferases, we found that the host intestinal B4galnt2 expression is not dependent on presence of the microbiota. Given the long-term maintenance of alleles influencing B4galnt2 expression by natural selection and the GI phenotypes presented here, we suggest that variation in B4galnt2 GI expression may alter susceptibility to GI diseases such as infectious gastroenteritis