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Of note, we demonstrate that the ASO treatment reversed the cardiac conduction abnormalities, and this correlated with restoration of Gja5 (connexin 40) expression in the heart. This is the first time that an ASO targeting a non-CUG sequence within the DMPK 3’UTR has demonstrated benefit on the key DM1 phenotypes of myotonia and cardiac conduction defects. Our data also shows for the first time, that ASOs may be a viable option for treating cardiac pathology in DM1. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.Transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa diagnosed in 2011-2014. We tested scenarios in which cases were missing at random, differentially by clinical characteristics or by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases and models provided evidence for superspreading. This is the first study to assess support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving superspreading. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020.BACKGROUND This study examined whether biological mechanisms linking dementia caregiving with an increased risk of coronary heart disease can be modified by psychosocial interventions and which caregivers might benefit the most from an intervention. METHODS Spousal dementia caregivers were randomized to 12-week treatment with either a behavioral activation intervention (i.e., Pleasant Events Program PEP; n=60), or an active control Information and Support (IS; n=63) condition. Indicators of caregiving stress were assessed pre-treatment and circulating cardiovascular biomarkers were measured pre- and post-treatment. RESULTS There were no significant changes in biomarker levels from pre- to post-treatment both by treatment condition and across all caregivers. Regardless of the treatment condition, exploratory regression analysis revealed that caregivers were more likely to show significant decreases in C-reactive protein (CRP) and D-dimer when their spouse had severe functional impairment; in interleukin (IL)-6 and CRP when they had greater distress due to care recipient’s problem behaviors; in tumor necrosis factor (TNF)-α when they had higher levels of negative affect; and in IL-6, CRP, TNF-α and D-dimer when they had higher personal mastery. Within the PEP group, caregivers with higher negative affect and those with higher positive affect were more likely to show a reduction in von Willebrand factor and D-dimer, respectively. Within the IS group, caregivers whose spouse had severe functional impairment were more likely to show a decrease in IL-6. CONCLUSIONS Unlike the average caregiver, caregivers high in burden/distress and resources might benefit from psychosocial interventions to improve cardiovascular risk, although these observations need confirmation. ClinicalTrials.gov #NCT02317523. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Mutations in the RYR1 gene are the most common cause of human congenital myopathies and patients with recessive mutations are severely affected and often display ptosis and/or ophthalmoplegia. In order to gain insight into the mechanism leading to extraocular muscle involvement, we investigated the biochemical, structural and physiological properties of eye muscles from mouse models we created knocked-in for Ryr1 mutations. Ex vivo force production in extraocular muscles from compound heterozygous RyR1p.Q1970fsX16 + p.A4329D mutant mice was significantly reduced compared to that observed in wild type, single heterozygous mutant carriers or homozygous RyR1p.A4329D mice. The decrease in muscle force was also accompanied by approximately a 40% reduction in RyR1 protein content, a decrease in electrically evoked calcium transients, disorganization of the muscle ultrastructure and a decrease in the number of calcium release units. Unexpectedly, the superfast and ocular-muscle specific myosin heavy chain-EO isoform was almost undetectable in RyR1p.Q1970fsX16 + p.A4329D mutant mice. The results of this study show for the first time that the extraocular muscle phenotype caused by the RyR1p.Q1970fsX16 + p.A4329D compound heterozygous Ryr1 mutations is complex and due to a combination of modifications including a direct effect on the macromolecular complex involved in calcium release and indirect effects on the expression of myosin heavy chain isoforms. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.OBJECTIVES To investigate the association between dietary fiber density (grams of fiber consumed per 100 kcal) with the gut-muscle axis in older adult men. HOIPIN-8 price DESIGN Cross-sectional study. SETTING Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16). PARTICIPANTS Older adult men (average age, 85y) from the MrOS study. MEASUREMENTS Men who were in the highest tertiles for dietary fiber density and the percentage of whole body lean mass were defined as T3T3 (n=42), whereas men who were in the lowest and intermediate tertiles for these variables were defined as T1T1 (n=32), T1T3 (n=24), and T3T1 (n=13), respectively. Additionally, measures of physical function, including the short physical performance battery (SPPB) score and grip strength were higher in T3T3 when compared with T1T1. Gut bacterial abundance was quantified with use of 16S v4 rRNA sequencing, and the bacterial functional potential was derived from the 16S data with PICRUSt. Chao1, ACE, Shannon, Simpson, and Fisher indices were used as measures of α-diversity.