Cooneyblanchard2053

Inhibition of Notch signaling has been shown to induce white to beige transformation of adipocytes and reduce the risk of obesity in mice. However, it remains unknown whether the metabolic benefits of Notch inhibition are dependent on uncoupling protein 1 (UCP1)-mediated thermogenesis and evolutionarily relevant in other mammalian species. Here we report the effect of Notch inhibition in adipocytes of pigs, which lost the UCP1 gene during evolution. Notch inhibition using a γ-secretase inhibitor dibenzazepine (DBZ) promoted beige adipogenesis and mitochondrial biogenic gene expression in porcine adipocytes. Moreover, encapsulation of DBZ into poly(lactide-co-glycolide) nanoparticles enabled rapid cellular internalization and enhanced bioactivity to achieve sustained Notch inhibition, thereby inducing beige-specific gene expression and reducing subcutaneous adipose tissue expansion in pigs. These results demonstrate for the first time a role of Notch signaling in regulating adipose plasticity in large animals, highlighting the therapeutic potential of targeting Notch signaling in obesity treatment.The prevalence of IgE-mediated food allergy is increasing at a rapid pace in many countries. The association of high food allergy rates with Westernized lifestyles suggests the role of gene-environment interactions, potentially underpinned by epigenetic variation, in mediating this process. Recent studies have implicated innate immune system dysfunction in the development and persistence of food allergy. These responses are characterized by increased circulating frequency of innate immune cells and heightened inflammatory responses to bacterial stimulation in food allergic patients. These signatures mirror those described in trained immunity, whereby innate immune cells retain a "memory" of earlier microbial encounters, thus influencing subsequent immune responses. Here, we propose that a robust multi-omics approach that integrates immunological, transcriptomic, and epigenomic datasets, combined with well-phenotyped and longitudinal food allergy cohorts, can inform the potential role of trained immunity in food allergy.Objectives This study was designed to assess the content and construct validity and reliability of the Quality of Nursing Doctoral Education (QNDE) instrument for nursing doctoral programmes with a research focus. Design A cross-sectional, survey study. Settings Using Qualtrics survey, the research team sent emails to potential participants providing a link to the study and the QNDE instrument. Participants A total of 234 faculty and doctoral students participated 17 faculty from 14 countries in the first stage; 111 faculty and 106 doctoral students from 20 countries in the second stage. Methods The content validity, internal consistency reliability, and construct validity of the four domains (program, faculty, resources, and evaluation) of the QNDE were examined in two stages. Data were collected from purposive samples of faculty and students between June 2018 and March 2019. Confirmatory factor analysis was conducted in ordinal scale using robust weighted least square mean and variance (WLSMV) adjusted estimator in MPlus 8. Results Content validity of the items in the four domains was accepted when the item showed content validity (I-CVI > 0.78). Internal consistency reliability in four domains was computed using Cronbach's alpha, α = 0.88 to 0.97. Construct validity of the QNDE was established by confirmatory factor analysis based on model fit statistics. Factor loading coefficients for all items in each domain were statistically significant (>0.5; p less then .001). Conclusions Participation of 234 faculty and doctoral students from 20 countries on four continents confirmed content validity, internal consistency reliability, and construct validity of the QNDE instrument. These findings support the credibility of this revised QNDE instrument for assessing the quality of nursing doctoral education with a research focus. This is a significant step forward in enhancing the capability for evaluating doctoral programmes.In response to the COVID-19 pandemic, most communities in the United States imposed stay-at-home orders to mitigate the spread of the novel coronavirus, potentially leading to chronic social isolation. During the third week of shelter-in-place guidelines, 1,013 U.S. adults completed the UCLA Loneliness Scale-3 and Public Health Questionnaire (PHQ-9). Loneliness was elevated, with 43% of respondents scoring above published cutoffs, and was strongly associated with greater depression and suicidal ideation. Loneliness is a critical public health concern that must be considered during the social isolation efforts to combat the pandemic.Background Mindfulness-based cognitive therapy (MBCT) is an increasingly popular treatment for major depression and anxiety disorder, but has shown inconsistent efficacy for bipolar disorder (BD). Therefore, we conducted a meta-analysis to assess the general efficacy of MBCT for BD. MV1035 mw Methods Ten studies were identified that fulfilled the current inclusion criteria, including three controlled and seven uncontrolled studies. The effects of MBCT on depression, anxiety, mania, stress, mindfulness ability, and emotional regulation were assessed by comparing psychometric scale scores within groups (pre- vs. post-intervention) across trials as well as between groups (control vs. MBCT) across controlled trials. Results Within-group comparison revealed a reduction in symptoms of depression (g = 0.37, 95%CI = 0.09-0.64, P = 0.009) and anxiety (g = 0.45, 95%CI =0.16-0.75, P = 0.002) following treatment compared to baseline. Stress symptoms were also significantly reduced (g = 0.39, 95%CI = 0.09-0.69, P = 0.01), mindfulnelimited and inconsistent, necessitating additional larger-scale studies and the development of post-intervention programs for sustained efficacy.Women can develop childbirth-related posttraumatic stress disorder (CB-PTSD) in at-term delivery with healthy baby outcome as well as following pre-term delivery and neonatal complications, a potential added stressor. No study compares risk factors of CB-PTSD associated with different infant outcomes. We investigated CB-PTSD risk factors by comparing women with or without neonatal complications. Analysis reveals the importance of antepartum and birth-related risk factors in CB-PTSD above and beyond child outcomes, suggesting childbirth is an independent stressor capable of evoking CB-PTSD.