Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3

Employers' views on the promotion of workplace health and wellbeing: A qualitative study

Background: The evidence surrounding the value of workplace health promotion in positively influencing employees' health and wellbeing via changes to their health behaviours is growing. The aim of the study was to explore employers' views on the promotion of workplace health and wellbeing and the factors affecting these views. Methods: Using a qualitative phenomenological approach, 10 focus groups were conducted with employers selected from a range of industries and geographical locations within Western Australia. The total sample size was 79. Results: Three factors were identified: employers' conceptualization of workplace health and wellbeing; employers' descriptions of (un)healthy workers and perceptions surrounding the importance of healthy workers; and employers' beliefs around the role the workplace should play in influencing health. Conclusions: Progress may be viable in promoting health and wellbeing if a multifaceted approach is employed taking into account the complex factors influencing employers' views. This could include an education campaign providing information about what constitutes health and wellbeing beyond the scope of occupational health and safety paradigms along with information on the benefits of workplace health and wellbeing aligned with perceptions relating to healthy and unhealthy workers

Life history, development, and host-parasite relations of Elsinoë panici Tiffany and Mathre

The host-pathogen relationship of Elsinoe panici (Tiffany and Mathre, 1961) on Panicum virgatum L. is particularly interesting because the only other Elsinoe species in this loculoascomycetous order, Myriangiales, parasitic on a member of the Gramineae is E. sacchari Lo (1964) on Saccharum officinarum L. However, Elsinoe spp. parasitize many herbaceous and woody dicotyledonous plants throughout the world;Since its description, no work has been conducted with E. panici. This study was undertaken to learn more of its geographic distribution, persistence, disease cycle, and development;E. panici occurs on native P. virgatum throughout Iowa, and has been recorded from Kalsow Prairie periodically for over 20 yr;In June, Sphaceloma conidia develop from acervuli in over- wintered stromata on wind dispersed litter or on old culms. Germ tubes penetrate between epidermal cells of young leaves, and 2 wk later tiny yellowish, subepidermal stromata are visible. Secondary conidia developed from acervuli on these stromata within 2 wk, spread the fungus to adjacent leaves. Stromata mature and become black, raised, shiny, ovoid-elongate patches, composed of thick-walled pseudoparenchymatous cells. Chlorosis or necrosis do not develop around stromata, which are visible on all leaves throughout the season. Acervuli, now appearing as white spots and opening by irregular tears in the epidermis over stromata, are common. Ascostromata develop from late July into September, primarily on lower leaves. They are tan-bronze, raised, ovoid-elongate, softer and more loosely structured than stromata and eventually contain asci and ascospores. Formed infrequently, ascostromata are typically supra-cuticular, irregularly multiloculate and uniascal. With the exception of possible spermagonia, no structures involved in ascus initiation were observed. Asci mature at different times, and at maturity, ascospores are discharged from the bitunicate asci and germinate directly by budding or by germ tubes;E. panici is a discrete pathogen, compatible with its host. Hyphae are intercellular, absorbing and replacing host cells, becoming intra- cellular only in epidermal, mesophyll, and colorless cells. Photo- synthetic bundle sheath cells restrict invasion into the vascular bundle. Cells in close proximity to infected cells remain intact.</p

Retention of Study Partners in Longitudinal Studies of Alzheimer Disease.

BACKGROUND: Study partners are required for all participants at Alzheimers Disease Research Centers (ADRCs). Study partners attitudes and beliefs may contribute to missed visits and negatively impact retention of participants in longitudinal AD studies. OBJECTIVE: Study partners (N = 212) of participants (Clinical Dementia Rating® [CDR]≤2) at four ADRCs were randomly surveyed to examine their facilitators and barriers to continued participation in AD studies. METHODS: Reasons for participation were analyzed with factor analysis and regression analysis. Effects of complaints and goal fulfillment on attendance were estimated with fractional logistic models. Open-ended responses were characterized with a Latent Dirichlet Allocation topic model. RESULTS: Study partners participated for personal benefit and altruism. They emphasized personal benefits more when their participants had a CDR &gt; 0 than when they had a CDR = 0. This difference declined with participant age. The majority of study partners rated their ADRC participation as positive and meeting their goals. Although half reported at least one complaint, very few regretted participating. Those who reported that ADRC participation fulfilled their goals or had fewer complaints were more likely to have perfect attendance. Study partners requested more feedback about test results and better management of study visits. CONCLUSION: Study partners are motivated by both personal and altruistic goals. The salience of each goal depends on their trust in researchers and the participants cognitive status and age. Retention may improve with perceived goal fulfillment and fewer complaints. Potential areas for improving retention are providing more information about the participants test results and better management of study visits