Magnussonfrandsen7117

Background In India, heterogenous tribal populations are grouped together under a common category, Scheduled Tribe, for affirmative action. Many tribal communities are closely associated with forests and difficult-to-reach areas and have worse-off health and nutrition indicators. However, poor population health outcomes cannot be explained by geography alone. Social determinants of health, especially various social disadvantages, compound the problem of access and utilisation of health services and undermine their health and nutritional status. The Towards Health Equity and Transformative Action on tribal health (THETA) study has three objectives (1) describe and analyse extent and patterns of health inequalities, (2) generate theoretical explanations, and (3) pilot an intervention to validate the explanation.     Methods For objective 1, we will conduct household surveys in seven forest areas covering 2722 households in five states across India, along a gradient of socio-geographic disadvantage. For objectivlations and finally examines if such approaches could help design equity-enhancing interventions to improve tribal health. Copyright © 2019 Srinivas PN et al.Objective To better characterize the neurologic and cognitive profile of patients with spinocerebellar ataxia 34 (SCA34) caused by ELOVL4 mutations and to demonstrate the presence of ELOVL4 cellular localization and distribution abnormalities in skin-derived fibroblasts. Methods We investigated a 5-generation French-Canadian kindred presenting with a late-onset cerebellar ataxia and recruited age- and education-matched controls to evaluate the presence of neurocognitive impairment. Immunohistochemistry of dermal fibroblasts derived from a patient's skin biopsy was performed. Results Patients had a late-onset slowly progressive cerebellar syndrome (mean age at onset 47 years; range 32-60 years) characterized by truncal and limb ataxia, dysarthria, hypometric saccades, and saccadic pursuits. No patient had past or current signs of erythrokeratodermia variabilis, which had previously been reported. Deucravacitinib MRI revealed cerebellar atrophy, with pontine atrophy (4 of 6 patients), and cruciform hypersignal in the pons (2 of 6 patients). Fluorodeoxyglucose-PET showed diffuse cerebellar hypometabolism in all 5 tested patients with subtle parietal hypometabolism in 3. Significant cognitive deficits were found in executive functioning, along with apparent visuospatial, attention, and psychiatric involvement. Immunohistochemistry of dermal fibroblasts showed mislocalization of the ELOVL4 protein, which appeared punctate and aggregated, supporting a dominant negative effect of the mutation on protein localization. Conclusions Our findings support the pathogenicity of ELOVL4 mutations in cerebellar dysfunction and provide a detailed characterization of the SCA34 phenotype, with neurocognitive changes typical of the cerebellar cognitive-affective syndrome. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.Objective To identify the phenotypic, neuroimaging, and genotype-phenotype expression of MYORG mutations. Methods Using next-generation sequencing, we screened 86 patients with primary familial brain calcification (PFBC) from 60 families with autosomal recessive or absent family history that were negative for mutations in SLC20A2, PDGFRB, PDGBB, and XPR1. In-depth phenotyping and neuroimaging investigations were performed in all cases reported here. Results We identified 12 distinct deleterious MYORG variants in 7 of the 60 families with PFBC. Overall, biallelic MYORG mutations accounted for 11.6% of PFBC families in our cohort. A heterogeneous phenotypic expression was identified within and between families with a median age at onset of 56.4 years, a variable combination of parkinsonism, cerebellar signs, and cognitive decline. Psychiatric disturbances were not a prominent feature. Cognitive assessment showed impaired cognitive function in 62.5% of cases. Parkinsonism associated with vertical nuclear gaze palsy was the initial clinical presentation in 1/3 of cases and was associated with central pontine calcifications. Cerebral cortical atrophy was present in 37% of cases. Conclusions This large, multicentric study shows that biallelic MYORG mutations represent a significant proportion of autosomal recessive PFBC. We recommend screening MYORG mutations in all patients with primary brain calcifications and autosomal recessive or negative family history, especially when presenting clinically as atypical parkinsonism and with pontine calcification on brain CT. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.Objective To investigate the genetic contribution to amyotrophic lateral sclerosis (ALS) and the phenotypic and genetic associations between ALS and psychiatric and cardiovascular disorders (CVD) we used the national registry data from Denmark linked to first-degree relatives to estimate heritability and cross-trait parameters. Methods ALS cases and 100 sex and birth-matched controls per case from the Danish Civil Registration System were linked to their records in the Danish National Patient Registry. Cases and controls were compared for (1) risk of ALS in first-degree relatives, used to estimate heritability, (2) comorbidity with psychiatric disorders and CVD, and (3) risk of psychiatric disorders and CVD in first-degree relatives. Results 5,808 ALS cases and 580,800 controls were identified. Fifteen percent of cases and controls could be linked to both parents and full siblings, whereas 70% could be linked to children. (1) We estimated the heritability of ALS to be 0.43 (95% CI, 0.34-0.53). (2) We found increased rates of diagnosis of mental disorders (risk ratio = 1.18; 95% CI, 1.09-1.29) and CVD in those later diagnosed with ALS. (3) In first-degree relatives of those with ALS, we found increased rate of schizophrenia (1.17; 95% CI, 0.96-1.42), but no evidence for increased risk CVD. Conclusions Heritability of ALS is lower than commonly reported. There is likely a genetic relationship between ALS and schizophrenia, and a nongenetic relationship between ALS and CVD. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.