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    Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature

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    Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of RAG-mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic RAG variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons. T helper 2 (TH2) cell skewing and a prominent inflammatory signature characterize Omenn syndrome, whereas more hypomorphic forms of RAG deficiency are associated with a type 1 immune profile both in blood and tissues. We used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis to define the cell lineage–specific contribution to the immunopathology of the distinct RAG phenotypes. These insights may help improve the diagnosis and clinical management of the various forms of the disease

    Mapping resilience and co-occurring theoretical constructs in nurses: a scoping review protocol

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    OBJECTIVE: The aim of this scoping review is to map the concept of resilience and its measurement along with co-occurring theoretical constructs within nursing research using the COVID-19 pandemic as a critical date range for the current evidence. INTRODUCTION: Resilience has a wide variety of definitions in research literature and is often measured through its co-occurring theoretical constructs. Nurse resilience is a key element in interventions targeting nurse well-being and has been tied to burnout and mental health. Resilience is influential in workforce stabilization and impactful to nurse retention both within a facility and within the field of nursing. This is significant given the worldwide nursing shortage and the attrition from the field. INCLUSION CRITERIA: This review will consider published and unpublished studies that investigate resilience and co-occurring theoretical constructs in nurses, excluding students. Studies published in English or Spanish will be considered for inclusion without restriction to setting or geographic location. All instruments that measure resilience will be considered for inclusion and mapped in conjunction with the co-occurring constructs. METHODS: Database searches from January 10, 2020, onwards will include CINAHL (EBSCOhost), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), Scopus, and LILACS. Unpublished studies and gray literature will be searched for on ProQuest Dissertations and Theses (ProQuest). The JBI methodology for scoping reviews will be followed. Extracted data will include publication details (authors, titles, year of publication), resilience measurement instruments, co-occurring theoretical constructs, participants, context, and concept. Extracted data will be presented in charts and tables supported by a narrative summary. REVIEW REGISTRATION: Open Science Framework https://osf.io/n2uge/

    Systemic bupropion treatment reduces long-access cocaine self-administration in male and female rats

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    Background: More than 1 million people in the United States meet the criteria for cocaine use disorder (CUD), and over 19,000 people died from cocaine-related overdoses in 2020, but there are currently no FDA-approved medications for the treatment of CUD. Bupropion is an antidepressant currently prescribed to treat depression and nicotine addiction that acts by inhibiting norepinephrine and dopamine transporters. Methods: In this study, we tested the effect of several doses of systemic bupropion on cocaine self-administration in male and female Wistar rats. In our first experiment, rats self-administered cocaine solution intravenously and were pretreated with systemic bupropion before self-administration sessions. In our second experiment, rats were pre-treated with bupropion before completing tests of locomotor activity and anxiety-like behavior. Results: We found that high doses of systemically administered bupropion (60 mg/kg) attenuated cocaine self-administration in male and female rats during extended-access (6 h) sessions. We also found that the highest dose (60 mg/kg) of systemic bupropion was more efficacious in females relative to males during the first hour of operant sessions. Systemic bupropion did not alter locomotor activity, inactive lever presses, or food intake. The Estrous cycle did not influence cocaine intake with or without bupropion. Conclusion: Our finding that bupropion attenuates cocaine self-administration suggests that bupropion may have promise for reducing cocaine use in humans

    Project ECHO® dermatology in the deep south: a comprehensive SWOT assessment

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    There are nearly 45,000 patients for each dermatologist in the rural State of Mississippi, causing many patients to wait months for an appointment in a city that may be hours away [1]. To address this critical gap, Project ECHO® (Extension for Community Healthcare Outcomes) was launched at the University of Mississippi Medical Center (UMMC) in 2020 to teach rural primary care providers (PCPs) to care for common skin conditions. PCPs present images of their patients in a once monthly video teleconference that provides immediate feedback. A SWOT analysis (Strengths, Weaknesses, Opportunities, and Threats) of the UMMC dermatology Project ECHO® was conducted to assess the efficacy of this approach. The greatest strength is the perception of value by attendees which is reflected by growing numbers of primary care physician participants. This engagement is tracked by the number of people who join the teleconference virtually. The greatest threat is the inability to motivate participants to complete post-teleconference surveys for program feedback. This limits the ability of the program to fully assess its efficacy and identify opportunities for improvement. Looking forward, UMMC plans to offer incentives for survey completion and expand Project ECHO’s reach by collaborating with other institutions to permit harmonization of metrics and facilitate data analysis for publications and grant applications

    Blocking the mineralocorticoid receptor prevents cardiac and mitochondrial dysfunction through the activation of NOX-4 in female hormone deprivation rats

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    Aim: Young women exhibit lower rates of cardiovascular disease (CVD) than age-matched men, a protective effect often attributed to estrogen\u27s influence on cardiac and mitochondrial function. The risk of CVD increases in post-menopausal women, likely due to estrogen deficiency and aldosterone\u27s negative effects, including those on mitochondria and other cellular targets. This study aimed to explore the link between estrogen deficiency and mitochondrial dysfunction in cardiac health. We hypothesized that in estrogen-deprived conditions, aldosterone could stimulate NADPH oxidase, leading to mitochondrial dysfunction, and reduced cardiac contractility. Methods: Wistar rats were divided into four groups: Sham, Ovariectomy-induced hormone deprivation (Ovx), Ovx with apocynin treatment, and Ovx with spironolactone treatment for 60 days. Results: Both apocynin and spironolactone countered the adverse effects of hormone deprivation by preserving myocardial contractility, improving cellular responses to calcium and isoproterenol, and normalizing the expression of key mitochondrial proteins. These compounds also attenuated the increase in reactive oxygen species (ROS) and maintained mitochondrial respiration rates. Conclusion: We concluded that estrogen deficiency contributes to cardiac oxidative stress via the NADPH oxidase and mitochondrial pathways. Apocynin and spironolactone offer significant protective effects, opening new avenues for treating cardiac issues related to estrogen deficiency

    Molecular Modification of Queen Bee Acid and 10-Hydroxydecanoic Acid with Specific Tripeptides: Rational Design, Organic Synthesis, and Assessment for Prohealing and Antimicrobial Hydrogel Properties

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    Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. We tested several amphiphiles among those containing moieties of hda or hdaa and isoleucine–leucine–aspartate (ILD-amidated) or IL-lysine (ILK-NH2). These tests were conducted to evaluate their prohealing and antimicrobial hydrogel properties. Our observation of their hydrogelation and hydrogel-rheology showed that they can form hydrogels with stable elastic moduli and injectable shear-thinning properties, which are suitable for cell and tissue repair and regeneration. Our disc-diffusion assay demonstrated that hdaa-ILK-NH2 markedly inhibited Staphylococcus aureus. Future research is needed to comprehensively evaluate the prohealing and antimicrobial properties of these novel molecules modified from hda and hdaa with tripeptides

    Exploring mental health in veterinary students: common stressors and effective coping strategies: a narrative review

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    INTRODUCTION: Veterinary students face significant challenges impacting their mental health and wellbeing. The rigorous academic curriculum, high expectations, and demanding clinical training create an environment of intense pressure and constant stress. This review explores the demographic and psychosocial variables influencing mental health outcomes, highlighting common stressors and coping strategies. METHODS: A systematic literature search was conducted using PubMed, CAB Abstracts, and Google Scholar. Studies published up to 2021 involving veterinary students were included. Twenty-one peer-reviewed studies met the inclusion criteria. Demographic data, stressors, mental health measures, and coping strategies were extracted and analyzed. Studies focused on various mental health aspects, including stress, anxiety, depression, and coping mechanisms. The final selection was based on relevance, quality, and comprehensiveness. RESULTS: The reviewed studies indicated that rigorous academic demands, high expectations, and clinical training contribute to elevated stress levels among veterinary students. Women reported higher levels of stress, anxiety, and depression compared to men, necessitating gender-specific interventions. Social support and relationship quality were crucial for mental wellbeing, with students in supportive environments experiencing lower stress. Effective coping strategies included exercise and social activities; whereas, harmful behaviors like substance misuse exacerbated mental health issues. Despite using mental health services, barriers such as stigma and lack of awareness hindered access for some students. CONCLUSION: The findings underscore the need for targeted support systems to enhance the mental health and resilience of veterinary students. Interventions to promote healthy coping mechanisms, reduce stigma, and improve access to mental health resources are essential. Veterinary schools should prioritize creating a supportive environment to ensure students can manage the demands of their profession while maintaining their mental health and wellbeing

    On the Table by J. M. Legier

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    48 x 36 Acrylic on Canvashttps://digitalscholar.lsuhsc.edu/art_med/1064/thumbnail.jp

    Over the Rainbow by J. M. Legier

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    48 x 36 Acrylic on Canvashttps://digitalscholar.lsuhsc.edu/art_med/1063/thumbnail.jp

    Petals & Positivity #4 by S. Cruise

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    Mixed Media: Glass, Metal, Illustration on Paper, and Florahttps://digitalscholar.lsuhsc.edu/art_med/1055/thumbnail.jp

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