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The author shares the passing of his mother. If he learned anything, it's this: He won't always be the one with answers. He won't be the one who fixes things, and that doesn't make him less of a doctor. In these moments, it's not about clinical roles or medical algorithms. It's about showing up -- as the son, the daughter, the sibling. Grief is slow, dirty, and obstinate. And when it arrives, it doesn't care about the number of degrees you hold or the number of lives you've affected. It just leaves you bare, confused, human.

Asthma is a heterogeneous disease that varies in clinical presentation, severity, and underlying biology but consistently involves airway remodeling (AR) and airway hyperresponsiveness (AHR), which is characterized by excessive airway narrowing in response to various stimuli. Airway smooth muscle (ASM) cells are primary contributors to airway hyperresponsiveness and bronchoconstriction. This review focuses on ASM cells and their role in asthma. We discuss the mechanisms by which ASM mediates AHR, increases airway thickness, and contributes to AR. Signaling through G protein-coupled receptors (GPCRs) regulates many ASM functions, including contraction, growth, and the synthetic activities that drive airway inflammation and remodeling. GPCR-dependent calcium flux serves as a key signaling axis controlling the contractile responses of ASM. Here we provide a comprehensive summary of the major GPCRs as well as other non-GPCRs identified in ASM cells. GPCR-induced calcium mobilization, downstream signaling and how it has been linked to specific ASM functions are also discussed. Furthermore, we highlight the clinical significance of targeting GPCRs in asthma therapy as well as recent development of novel therapeutics in the management of asthma. Thus, this review provides a comprehensive overview of airway smooth muscle in the context of asthma pathophysiology.

IntroductionBurnout among healthcare professionals remains a critical public health issue linked to impaired cognition, emotional exhaustion and diminished clinical performance. Structured breathing practices have demonstrated promise in improving autonomic regulation and cerebral oxygenation, yet their feasibility, acceptability and implementation in real-world healthcare settings remain underexplored.ObjectivesThis single-arm pilot feasibility trial aims to evaluate the feasibility, acceptability and implementation appropriateness of a structured breathing-based intervention for healthcare professionals across community-based Mayo Clinic Health System (MCHS) sites. Secondary objectives include assessing usability and engagement with the mobile breathing platform, while exploratory analyses will describe magnitude of variability and feasibility of collecting psychological and cerebral haemodynamic measures. This study will commence in November 2025 and is expected to be completed by June 2026.Methods and analysisA total of 40 clinicians (MD/DO/MBBS/PA) and nurses reporting moderate or greater burnout will be enrolled across four MCHS sites. Participants will complete a 4-month structured breathing programme delivered primarily online, supported by a mobile application for practice tracking. Assessments will occur at baseline, 2 months and 4 months, with functional near-infrared spectroscopy (fNIRS) measures of cerebral oxygenation collected at baseline and 4 months in a population subset. Primary outcomes include (1) recruitment yield, retention and adherence rates; (2) acceptability and participant satisfaction (survey and qualitative feedback); and (3) implementation appropriateness measured by the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). Secondary outcomes include digital engagement and usability through mobile analytics and the System Usability Scale. Exploratory outcomes are psychological indicators (burnout, depression, anxiety, perceived stress, sleep, fatigue, professional fulfilment and resilience) and physiological endpoints (fNIRS). Analyses will be descriptive, summarising feasibility metrics with 95% CIs. Progression criteria (recruitment≥75%, retention≥80%, adherence≥70%, AIM/IAM/FIM≥4.0) will determine readiness for a definitive hybrid effectiveness–implementation trial.Ethics and disseminationThe study is approved by the Mayo Clinic Institutional Review Board (IRB # 25-009320). All participants will provide informed consent. Study procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be securely stored in REDCap and disseminated through peer-reviewed publications and scientific conferenceTrial registration numberNCT07218458.

Background: News articles, commentaries, and opinion articles have suggested that ongoing social distancing measures coupled with economic challenges during COVID-19 may worsen stress, affective state, and substance use across the globe. We sought to advance our understanding of the differences between individuals who change their substance use patterns during a public health crisis and those who do not. Methods: Cross-sectional survey of young adults (18–25 years of age) assessing respondent characteristics and vaping, tobacco, alcohol, and/or marijuana use. We calculated prevalence estimates, prevalence changes, and prevalence ratios with associated 95% confidence intervals and looked for differences with the chi-square test. Results: Of the total sample, 53.2% (n = 542/1018) young adults reported vaping or using tobacco, alcohol, and/or marijuana. Among the 542 respondents reporting use, 34.3% reported a change in their use patterns. Among respondents reporting changes in substance use patterns during the pandemic (n = 186), 68.8% reported an increase in alcohol use, 44.0% reported a decrease in vaping product use, and 47.3% reported a decrease in tobacco product use due to COVID-19. Substance use changed significantly for respondents with increasing degree of loneliness (continuous loneliness score: prevalence ratio = 1.12, 95% confidence interval = 1.01–1.25), anxiety (prevalence ratio = 1.45, 95% confidence interval = 1.14–1.85), and depression (prevalence ratio = 1.44, 95% confidence interval = 1.13–1.82). Conclusion: Self-reported substance use among young adults was observed to change during a pandemic, and the degree of loneliness appears to impact these changes. Innovative strategies are needed to address loneliness, anxiety, depression, and substance use during global health crises that impact social contact.

Obesity and hyper-intestinal permeability are interconnected. This study is designed to evaluate the ability of Mangifera indica seed kernel extract (MESK) in restoring the intestinal barrier and preventing obesity and associated metabolic complications in a high-fat diet-induced obese mouse model. Four groups of Swiss albino mice: (1) normal diet (ND), (2) high-fat diet (HFD), (3) HFD + Orlistat (100 µg/kg), and (4) HFD + MESK (75 µg/kg), were used to monitor various biochemical parameters associated with metabolic syndrome (glucose, total cholesterol, triglycerides) and body weight in an eight-week-long study. In vivo intestinal permeability was determined by the FITC-dextran method. Interestingly, MESK significantly reduced HFD-induced body weight gain, hepatic lipid accumulation, hepatic fibrosis, hyperglycemia, and dyslipidemia. Additionally, MESK treatment restored the expression of tight junction protein Zonula Occludens-1 (ZO-1) and Claudin-1 and hence prevented increased intestinal permeability induced by a high-fat diet. Moreover, it also increased the expression of potent satiety molecule Nesfatin-1 in the mouse jejunum. Our results, for the first time, establish MESK as a nutraceutical which prevents disruption of the intestinal barrier and thereby intercepts the adverse consequences of compromised intestinal permeability such as obesity, hyperglycemia, dyslipidemia, and systemic inflammation.

As the age of the world's population continues to increase it is important to investigate behaviors, such as alcohol consumption, that may negatively impact the health of the older population. In the present study, aged, young adult and adolescent female and male C57BL/6J mice underwent a measure of acute alcohol withdrawal via a handling induced convulsion study followed by a drinking in the dark procedure to measure alcohol self-administration. We report that aged animals enter acute alcohol withdrawal later than younger animals as measured by later onset of handling induced convulsions. The later onset is likely due to reduced alcohol metabolism. Furthermore, aged animals consumed significantly less alcohol in the drinking in the dark paradigm but had similar blood alcohol concentrations compared to younger animals. The current work demonstrates for the first time differential alcohol self-administration and acute alcohol withdrawal in aged animals compared to younger animals.

The advent of long-term implants has increased the urgent need for self-powered biomedical devices. Utilize enzymes to expedite the process of biofuel oxidation. These systems frequently make use of glucose oxidase. A possible solution involves glucose biofuel cells powered by the glucose found in physiological fluids. Biocompatible substances like carbon electrode designs help to transport electrons from the biological reactions to the external circuit as efficiently as possible while maximizing surface area. Despite advances in implantable electrodes, developing miniaturized and flexible electrodes remains challenging. In this work, a metal-coated flexible carbon thread and foam bioelectrode are fabricated and successfully implanted inside a living and freely moving rat. These electrodes are prepared using gold nanostructures as electron enhancers, a negatively charged conducting polymer, a biocompatible redox mediator, and enzymes as biocatalysts. The carbon foam-based enzymatic biofuel cell produces in vitro and in vivo settings, generates a power density of 165 µW/cm 2 and 285 µW/cm 2 , and the carbon thread-based fuel cell produces a power density of 98 µW/cm 2 and 180 µW/cm 2 in vitro and in vivo environments, respectively. This work paves the way for the possible use of inexpensive electrodes for subdermal implantable microsystems.

Objectives/Goals: 1. Build a network of stakeholders (WomenWise) empowered as a Community Advisory Board (CAB). 2. Expand knowledge about patient-centered outcomes research (PCOR) and comparative effectiveness research (CER), specifically related to alcohol use in women. 3. Report facilitators, barriers, and CAB members’ experience with developing WomenWise. Methods/Study Population: Female stakeholders from nonprofit organizations (NPOs), persons and family members with lived experience with alcohol misuse, and health professionals were organized into a CAB (n = 17). CAB members receive education on PCOR/CER and sex-related disparities in alcohol treatment and create resources for large-scale community dissemination. Members will also host partnered learning sessions in their community alongside NPOs to teach the public about alcohol misuse in women and engage in PCOR/CER. Surveys and descriptive statistics assess CAB members’ understanding of educational material, engagement, and project feasibility. A Governance Council of co-investigators, collaborators, patient representatives, and a CAB chairperson oversee project progress and completion. Results/Anticipated Results: Two CAB meetings were completed thus far, with five meetings continuing into the next year. The first two CAB meetings were attended by 14/17 (82%) of members. After receiving education on Research Fundamentals, among those completing the survey (11/14), the knowledge assessments scores were very high. The Governance Council began planning the first large-scale community dissemination symposium to be held in Summer 2025, and three additional CAB meetings will be held before the ACTS conference poster presentation. We will share data on the process to initiate this capacity-building project, PCOR/CER education, stakeholder engagement and feedback, challenges and responses, and overall evaluation of the project’s feasibility and sustainability. Discussion/Significance of Impact: Historically, women have been unrepresented in alcohol misuse research, and studies rarely analyze sex and gender differences. WomenWise, a network of women stakeholders knowledgeable about these disparities and PCOR/CER, will lead efforts to educate community members about alcohol treatment disparities and engage them in future research.

Alcohol misuse among women has risen compared to men. Women experience barriers to engaging in patient-centered comparative effectiveness research (CER) that, in turn, limits the evidence base for addressing alcohol misuse in this population. In this manuscript, we describe WomenWise, a community-partnered project and outline how we co-developed community focused CER training curriculum and collaboratively planned future partnered learning sessions (PLSs) with Community Advisory Board (CAB) feedback. Through this approach we aim to empower women to contribute to future patient-centered CER and enhance the stakeholder capacity for future patient-centered research.

Individuals living in rural communities experience substantial geographic and infrastructure barriers to attaining health equity in accessing tobacco use cessation treatment. Social media and other digital platforms offer promising avenues to improve access and overcome engagement challenges in tobacco cessation efforts. Research has also shown a positive correlation between faith-based involvement and a lower likelihood of smoking, which can be used to engage rural communities in these interventions. This study aimed to develop and beta test a social intervention prototype using a Facebook (Meta Platforms, Inc) group specifically designed for rural smokers seeking evidence-based smoking cessation resources. We designed a culturally aligned and faith-aligned Facebook group intervention, FaithCore, tailored to engage rural people who smoke in smoking cessation resources. Both intervention content and engagement strategies were guided by community-based participatory research principles. Given the intervention's focus on end users, that is, rural people who smoked, we conducted a beta test to assess any technical or usability issues of this intervention before any future trials for large-scale implementation. No critical beta test technical and usability issues were noted. Besides, the FaithCore intervention was helpful, easy to understand, and achieved its intended goals. Notably, 90% (9/10) of the participants reported that they tried quitting smoking, while 90% (9/10) reported using or seeking cessation resources discussed within the group. This study shows that social media platform with culturally aligned and faith-aligned content and engagement strategies delivered by trained moderators are promising for smoking cessation interventions in rural communities. Our future step is to conduct a large pilot trial to evaluate the intervention's effectiveness on smoking cessation outcomes.