Explore the vast range of titles available.

Suicide rates have risen among emerging adults of Asian descent, yet limited research has explored risk and protective factors within this population. Grounded in the Interpersonal Theory of Suicide, this study examined the associations between coping orientations (i.e., problem-focused, emotion-focused, and avoidant) and strategies (i.e., gratitude, self-compassion, and search for meaning in life) and suicide risk (i.e., perceived burdensomeness and thwarted belongingness) among emerging adults of Asian descent (N = 429). Multiple linear regression models were used to assess these associations while controlling for relevant demographic variables. Problem-focused coping and gratitude were negatively associated with perceived burdensomeness and thwarted belongingness, whereas emotion-focused and avoidant coping were positively associated with perceived burdensomeness. Avoidant coping was also positively associated with thwarted belongingness, whereas self-compassion was negatively associated with thwarted belongingness. These findings underscore the importance of culturally responsive interventions that promote active coping and emotional resilience in addressing perceived burdensomeness and thwarted belongingness and addressing suicide risk factors.

IntroductionIntentional injuries can be broadly classified into those that are self-inflicted (eg, suicide, self-harm), and those that are inflicted by others (eg, homicide, assault). Many risk factors are the same for all intentional injuries. It is widely accepted that there needs to be a public health approach to self-harm and interpersonal violence prevention, including surveillance of presentations to emergency departments. Self-harm and interpersonal violence are important causes of morbidity and mortality in Wales. Interpersonal violence surveillance is already operationalised in Wales, but variables are limited and case ascertainment may not be complete. There is no self-harm register. The aim of this study is to understand the utility of existing systems in North Wales that collect data about self-harm and interpersonal violence, and how a registry could be implemented to address any unmet needs.Methods and analysisThe project consists of five work packages. First, process mapping will be used to understand the pathways by which patients access emergency care, and how data are collected about patients. Second, routinely collected data will be explored to understand the burden of disease, and the strengths and limitations of existing data collection systems. Third, semi-structured interviews will be completed with stakeholders to understand their needs and experiences. Fourth, semi-structured interviews with third sector organisations which work with people with lived experience of self-harm or interpersonal violence will explore the acceptability of data collection. Fifth, a method will be developed that would enable economic evaluation of a self-harm and interpersonal violence register.Ethics and disseminationResults will be used to understand whether a self-harm and interpersonal violence registry is required in Wales. The results have the potential to influence local and national strategy on intentional injury prevention. Results will be disseminated to local services, regional and national programme teams, and published as a peer-reviewed journal article.

Exosomes, an acellular regenerative biologic, have demonstrated success in resolving vaginal mesh exposures after pelvic reconstructive surgery; little data exists for their use for prevention of mesh-based complications. This study evaluated the early efficacy of purified exosome product (PEP) for preventing mesh exposures. Ten Yorkshire-crossed pigs underwent mesh sacrocolpopexy with two high-risk-for-exposure configurations: mesh fold ventrally, vaginotomy dorsally. PEP in hyaluronic acid (HA) or HA-only (control) was injected at baseline. Twelve weeks later, animals were euthanized and evaluated for mesh exposure and histologic changes. None of the PEP-treated tissues demonstrated mesh exposure (0/6); all control group animals experienced a mesh exposure (4/4 mesh fold configuration, 2/4 vaginotomy configuration). Control tissues exhibited higher fibrosis (vaginotomy fibrosis score: median(IQR); 3(3,3) control, 2(1,2) PEP; p  = 0.03) and greater epithelial apoptosis (mesh fold TUNEL+area fraction: median 18.9 control vs 0.43 PEP; p  = 0.02). Our study demonstrated that PEP treatment mitigated the risk of early mesh exposure.

Abstract Actin-binding protein Profilin1 is an important regulator of actin cytoskeletal dynamics in cells and critical for embryonic development in higher eukaryotes. The objective of the present study was to examine the consequence of loss-of-function of Pfn1 in vascular endothelial cells (ECs) in vivo. We utilized a mouse model engineered for tamoxifen-inducible biallelic inactivation of the Pfn1 gene selectively in EC (Pfn1EC-KO). Widespread deletion of EC Pfn1 in adult mice leads to severe health complications presenting overt pathologies (endothelial cell death, infarct, and fibrosis) in major organ systems and evidence for inflammatory infiltrates, ultimately compromising the survival of animals within 3 weeks of gene ablation. Mice deficient in endothelial Pfn1 exhibit selective bias toward the proinflammatory myeloid-derived population of immune cells, a finding further supported by systemic elevation of proinflammatory cytokines. We further show that triggering Pfn1 depletion not only directly upregulates proinflammatory cytokine/chemokine gene expression in EC but also potentiates the paracrine effect of EC on proinflammatory gene expression in macrophages. Consistent with these findings, we provide further evidence for increased activation of Interferon Regulatory Factor 7 (IRF7) and STAT1 in EC when depleted of Pfn1. Collectively, these findings for the first time demonstrate a prominent immunological consequence of loss of endothelial Pfn1 and an indispensable role of endothelial Pfn1 in mammalian survival unlike tolerable phenotypes of Pfn1 loss in other differentiated cell types.

BackgroundPancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer and closely associated with cachexia. Characterized by irreversible wasting of skeletal muscles with or without fat loss and systemic inflammation, cachexia reduces the efficacy of various anti-cancer interventions and enhances the morbidity of PDAC. Recent research suggests that cachexia confers resistance to immune-checkpoint inhibition in several cancers, indicating an intricate crosstalk with immunological pathways. The bidirectional relationship between cachexia and the immune system in PDAC is poorly understood, necessitating the development of novel preclinical models.MethodsThe SIYRYYGL (SIY) antigen-expressing PK5L1948 tumor cells, derived from KPC-LSIY mice (KrasLSL-G12D/ + Tp53LSL-R172H/ + Pdx1-Cre/R26LSL-LSIY), were orthotopically injected into the pancreas of male and female C57BL/6J mice and hallmarks of cachexia were assessed after 21 days. Tumor weight, terminal tumor-adjusted body weight, skeletal muscle, adipose tissue, liver and spleen masses, expression of proteolytic markers and grip strength were recorded to validate the cachectic phenotype of the PK5L1948 tumor-bearing model. Plasma cytokine and chemokine concentrations were quantified by Luminex assay. High-dimensional flow cytometry was used to investigate changes in tumor-infiltrating immune populations in cachectic miceResultsMale tumor-bearing mice exhibited a severely cachectic phenotype, as assessed by >5% decrease in terminal tumor-adjusted body weight and >50% reduction in fat mass. Additionally, PK5L1948 tumors induced significant loss of lean muscle mass and grip strength as well an increase in the liver and spleen masses in males (n=10, p<0.05). Female tumor-bearing mice did not lose muscle mass but demonstrated >30% fat loss and splenomegaly (n=10). The E3 ubiquitin ligase, Fbxo32, was upregulated in skeletal muscles of tumor-bearing mice of both sexes (n=5), corroborating the onset of skeletal muscle atrophy at the molecular level. Plasma cytokine concentrations, particularly TNF and T-cell associated inflammatory mediators were differentially upregulated in males and females (n=10/group, p<0.05), suggesting functional differences in immune cells as potent drivers of sex-bias in PK5L1948-driven cachexia. Importantly we demonstrated the ability of this model to comprehensively investigate the intra-tumoral abundance of various innate and adaptive immune populations, particularly the functional subsets of SIY antigen-specific T cells (effector, memory and exhausted), opening a window of opportunity to test various immunotherapeutic interventions in the cachectic background.ConclusionsThe PK5L1948 orthotopic PDAC model exhibits prominent hallmarks of cachexia and serves as a novel platform for investigating antigen-specific T cell responses in pancreatic cancer cachexia. Overall, this study has yielded an effective and versatile tool for pre-clinical immunological studies in the context of cachexia.Ethics ApprovalAll animal protocols were approved by the Institutional Animal Care and Use Committee (IACUC) at The Ohio State University (2009A0178-R5) and mice were treated in accordance with institutional guidelines for animal care. The Ohio State University Laboratory Animal Shared Resource is an Association for Assessment and Accreditation of Laboratory Animal Care International accredited program that follows Public Health Service policy and guidelines. All other experiments were completed under the research protocols (2014R00000086; 2013R00000056) approved by the Ohio State University Institutional Biosafety Committee.

This data descriptor describes a repository of openly shared data from an experiment to assess inter-individual differences in default mode network (DMN) activity. This repository includes cross-sectional functional magnetic resonance imaging (fMRI) data from the Multi Source Interference Task, to assess DMN deactivation, the Moral Dilemma Task, to assess DMN activation, a resting state fMRI scan, and a DMN neurofeedback paradigm, to assess DMN modulation, along with accompanying behavioral and cognitive measures. We report technical validation from n=125 participants of the final targeted sample of 180 participants. Each session includes acquisition of one whole-brain anatomical scan and whole-brain echo-planar imaging (EPI) scans, acquired during the aforementioned tasks and resting state. The data includes several self-report measures related to perseverative thinking, emotion regulation, and imaginative processes, along with a behavioral measure of rapid visual information processing. Technical validation of the data confirms that the tasks deactivate and activate the DMN as expected. Group level analysis of the neurofeedback data indicates that the participants are able to modulate their DMN with considerable inter-subject variability. Preliminary analysis of behavioral responses and specifically self-reported sleep indicate that as many as 73 participants may need to be excluded from an analysis depending on the hypothesis being tested. The described data are distributed with and build upon the comprehensive neuroimaging and deep phenotyping available in the enhanced Nathan Kline Institute, Rockland Sample. As limited information is presently available about individual differences in the capacity to directly modulate the default mode network, these data provide a unique opportunity to examine DMN modulation ability in relation to numerous phenotypic characteristics.