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Billions of cells are eliminated daily from our bodies1-4. Although macrophages and dendritic cells are dedicated to migrating and engulfing dying cells and debris, many epithelial and mesenchymal tissue cells can digest nearby apoptotic corpses1-4. How these non-motile, non-professional phagocytes sense and eliminate dying cells while maintaining their normal tissue functions is unclear. Here we explore the mechanisms that underlie their multifunctionality by exploiting the cyclical bouts of tissue regeneration and degeneration during hair cycling. We show that hair follicle stem cells transiently unleash phagocytosis at the correct time and place through local molecular triggers that depend on both lipids released by neighbouring apoptotic corpses and retinoids released by healthy counterparts. We trace the heart of this dual ligand requirement to RARγ-RXRα, whose activation enables tight regulation of apoptotic cell clearance genes and provides an effective, tunable mechanism to offset phagocytic duties against the primary stem cell function of preserving tissue integrity during homeostasis. Finally, we provide functional evidence that hair follicle stem cell-mediated phagocytosis is not simply redundant with professional phagocytes but rather has clear benefits to tissue fitness. Our findings have broad implications for other non-motile tissue stem or progenitor cells that encounter cell death in an immune-privileged niche.

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Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.

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INTRODUCTION: Deaths from drug overdoses are rising dramatically in the United States. Treatment for opioid use disorders may include behavioral treatments as well as medications for opioid use disorders (MOUD). Buprenorphine can be prescribed by physicians, nurse practitioners (NPs), other advanced practice registered nurses (APRNs), and physician assistants (PAs) and required a training and a federal waiver until recently. The number of NP MOUD prescribers grew steadily over the past decade, but research has identified state-level scope of practice regulations as a barrier to NP MOUD prescribing. This article explores the contributions of, and remaining barriers faced by NP and other APRN MOUD prescribers. We describe qualitative findings from a study of NPs and other key stakeholders involved in MOUD treatment in four states with two differing levels of regulatory structure. METHODS: In this qualitative study, we conducted site visits and semi-structured interviews with NPs and other APRNs, physicians, clinic managers, and regulators in four states including New Mexico and West Virginia (full practice authority for NPs), and Ohio and Michigan (which require physician supervision). Interview notes were entered into a qualitative software package and coded and reviewed by two members of the research team. Data were grouped into key themes. RESULTS: A total of 76 participants participated in individual or small group interviews in the four states. We found key themes and several subthemes that describe NP practice in MOUD. Participants described key contributions of NP engagement in MOUD, including increasing access, serving rural areas, the unique role of psychiatric NPs, and the value of the nursing model of care in working with people with substance use disorders (SUD). Participants also identified barriers including scope of practice regulations, other regulatory barriers, stigma, and lack of supportive services to address psychosocial needs. CONCLUSIONS: The waiver requirements were eliminated at the end of 2022 in federal budget legislation. Other barriers for NP and other APRN prescribers remain and should be addressed in practice, and in state and federal regulations. Research needs to explore the impact of the waiver elimination on MOUD prescribing and access to services.

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INTRODUCTION: Buprenorphine, an effective medication for opioid use disorder (MOUD), reduces opioid-related harms including overdose, but a significant gap exists between MOUD need and treatment, especially for marginalized populations. Historically, low MOUD treatment capacity is rising, driven by advanced practice registered nurses (APRNs). A graduate nursing course was designed to increase equitable buprenorphine treatment delivery by APRNs. We report on baseline findings of a curriculum evaluation study with a pretest-posttest design. DESIGN: Computerized surveys assessed trainee satisfaction with the course, trainee knowledge for providing MOUD, and trainee satisfaction in working with people who use drugs. METHODS: Quantitative survey results utilizing Likert scales are presented. RESULTS: Baseline precourse surveys revealed less than half (44%) of APRN students agreed/strongly agreed that they had a working knowledge of drugs and drug-related problems and 37% agreed/strongly agreed that they knew enough about the causes of drug problems to carry out their roles when working with people who use drugs. Approximately two thirds of APRN students agreed/strongly agreed that they want to work with people who use drugs (63%), that it is satisfying to work with people who use drugs (66%), and that it is rewarding to work with people who use drugs (63%). Nearly all students reported high satisfaction with the course. CONCLUSION: APRN students reported high satisfaction with a novel course grounded in health equity that has potential to reduce health disparities and accelerate the closure of the MOUD treatment gap, particularly for racial/ethnic minorities, rural populations, and transition-age youth.

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BACKGROUND: Rates of cannabis use are increasing in the United States, likely as a result of changes in societal attitudes and expanding legalization. Although many patients report wanting to discuss the risks and benefits of cannabis use with their clinical providers, many providers hold conflicting beliefs regarding cannabis use and often do not engage patients in discussion about cannabis. This dilemma is underscored by the limitations imposed on cannabis related research, and lack of empirically based best-practice guidelines for clinicians when addressing cannabis use with patients. OBJECTIVES: We aimed to briefly summarize clinician and patient attitudes toward cannabis use and review current clinical guidelines and provide suggestions to assist health care providers and clinicians in increasing their comfort and skill in discussing cannabis use with patients. METHODS: A narrative review on attitudes toward cannabis use and clinical guidelines was performed to summarize the literature and provide evidence-based recommendations. RESULTS: Attitudes toward cannabis use have been shaped by personal and political factors and contribute to clinician hesitance in speaking with patients about the topic. Administrative barriers have hindered the development of clearer public health guidelines that might enable the dissemination of evidence-based information on the health effects of cannabis use and might ultimately lead to better health outcomes. CONCLUSION: Not discussing cannabis use with patients may be a crucial missed opportunity for harm reduction. In the absence of empirically supported best-practice guidelines, a person-centered approach can facilitate conversations on the harms and benefits of cannabis use.

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Macrophages and dendritic cells have long been appreciated for their ability to migrate to and engulf dying cells and debris, including some of the billions of cells that are naturally eliminated from our body daily. However, a substantial number of these dying cells are cleared by 'non-professional phagocytes', local epithelial cells that are critical to organismal fitness. How non-professional phagocytes sense and digest nearby apoptotic corpses while still performing their normal tissue functions is unclear. Here, we explore the molecular mechanisms underlying their multifunctionality. Exploiting the cyclical bouts of tissue regeneration and degeneration during the hair cycle, we show that stem cells can transiently become non-professional phagocytes when confronted with dying cells. Adoption of this phagocytic state requires both local lipids produced by apoptotic corpses to activate RXRα, and tissue-specific retinoids for RARγ activation. This dual factor dependency enables tight regulation of the genes requisite to activate phagocytic apoptotic clearance. The tunable phagocytic program we describe here offers an effective mechanism to offset phagocytic duties against the primary stem cell function of replenishing differentiated cells to preserve tissue integrity during homeostasis. Our findings have broad implications for other non-motile stem or progenitor cells which experience cell death in an immune-privileged niche.

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Slow and incremental changes in federal and state drug policies are neither meeting treatment needs nor reversing yearly increases in drug-related mortality. U.S. drug policies convey confounding messages that non-sanctioned substance use leads to health problems that need treatment while simultaneously being legal problems that must be punished. As a result, drug treatments remain a sequestered component of health care, with onerous treatment requirements for patients and providers that act as barriers to the treatment that policies seek to allow. A new direction in drug policy is needed that broadens rather than restricts access to care and that also focuses on prevention. Policies must consider the totality of health and wellness, not just "last resort" safety nets for urgent needs. For substantive change in drug-related morbidity and mortality, forward-thinking policy must focus more on addiction prevention and address the known risks of developing a substance use disorder. [Journal of Psychosocial Nursing and Mental Health Services, 61(6), 7-10.].

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Background: Patients experiencing homelessness have higher rates of substance use and related mortality, often driven by opioid overdose. Conversely, opioid use disorder (OUD) is a leading risk factor for homelessness. Our goal was to test the efficacy of an electronic health record (EHR) screen in identifying this vulnerable population during hospitalization and to assess the feasibility of a bundled intervention in improving opioid safety. Methods: We assessed patients' housing status, substance use, previous MOUD treatment, barriers to MOUD treatment and readiness to take MOUD in and out of the hospital. For each post discharge follow up call, patients were asked about their MOUD status, barriers accessing treatment, current substance use, and housing status. We also assessed team members perceptions and experiences of the study. Results: We enrolled 32 patients with housing insecurity and OUD. The mean age was 44, the majority self-identified as male (78%), and mostly as White (56%) or Black (38%). At each follow up within the 6-months post-discharge, reach rates were low: 40% of enrollees answered at least 1 call and the highest reach rate (31% of patients) occurred at week 4. At the third and sixth-month follow ups, >50% of subjects still taking MOUD were also using opioids. Conclusion: Our clinician augmented EHR screen accurately identified inpatients experiencing OUD and PEH. This intervention showed high rates of attrition among enrolled patients, even after providing cellphones. The majority of patients who were reached remained adherent to MOUD though they reported significant barriers.

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BACKGROUND: Opioid misuse is a major public health concern in the United States. Opioid agonist medications are evidence-based treatments for opioid use disorders (OUD) that can be prescribed by advance practice registered nurses (APRNs) with prescriptive authority and appropriate training. PURPOSE: Article examines factors influencing preparation to provide medications for opioid use disorder (MOUD) in APRN education. METHODS: Data from semi-structured interviews addressing the role of education in preparing APRNs to provide MOUD were grouped into key themes using thematic analysis. Data were collected in a mixed methods study in four states with high opioid overdose deaths whose main findings were previously published. FINDINGS: Two overarching themes emerged: "addressing attitudes" and "curriculum change." Sub-themes include affective barriers to providing OUD treatment; motivation to respond to the OUD crisis; and attitude change through experience with MOUD. DISCUSSION AND CONCLUSION: APRNs can play a key role in reducing the harms caused by OUD. Attention to attitudinal issues, such as stigma, toward people using opioids is important in educating APRNs about providing MOUD.

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INTRODUCTION: Drug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled with stark health inequities demands a close examination of opioid use disorder (OUD) treatment barriers and swift consideration of policy changes. DESIGN: The aim of this buprenorphine policy analysis is to summarize existing buprenorphine barriers and present policy solutions to improve access and actualize the contributions of Advanced Practice Registered Nurses (APRNs). METHODS: The policy analysis follows five sequential steps: (1) defining the problem, (2) identifying key stakeholders, (3) assessing the landscape of relevant policies, (4) describing viable policy options, and (5) making final recommendations. RESULTS: Although there are laudable efforts to improve buprenorphine access, such as the new buprenorphine guidelines issued in April 2021, without larger-scale changes to federal, state, and scope of practice laws, overdose rates will continue to rise. We recommend a multipronged policy approach to improve buprenorphine treatment access, including eliminating the DEA X waiver, improving OUD education, and adopting full practice authority for APRNs in all states. CONCLUSION: Incremental change is no longer sufficient to address opioid overdose deaths. Bolder and coordinated policy action is possible and necessary to empower the full clinical workforce to apply evidence-based life-saving treatments for OUD. The critical contributions of nurses in advancing equitable access to OUD care are emphasized in the National Academy of Medicine's Report, Future of Nursing: Charting a Path to Achieve Health Equity. Nurses are named as instrumental in improving buprenorphine access. Policy changes that acknowledge and build on evidence-based treatment expansion strategies are sorely needed. CLINICAL RELEVANCE: One of the most robust tools to combat opioid overdose deaths is buprenorphine, a partial opioid agonist, and gold standard medication treatment for OUD, but only 5% of the prescribing workforce possess the required Drug Enforcement Agency (DEA) X waiver. A growing body of evidence demonstrates that Advanced Practice Registered Nurses are accelerating the growth in waiver update and buprenorphine use, despite the considerable barriers and limitations described in this policy analysis.

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OBJECTIVE: Physician supervision of nurse practitioners (NPs) was temporarily waived in Massachusetts in response to a state of emergency due to the COVID-19 pandemic. The authors examined the impact of the scope-of-practice changes and pandemic-related demands on psychiatric mental health NPs (PMHNPs) during the state's first COVID-19 surge. METHODS: A mixed-methods Web-based survey was conducted in May and June of 2020. Fisher's exact test was used to compare associations across certification types, and inductive content analysis was applied to open-ended responses. RESULTS: The survey response rate was 41% (N=389 of 958), consisting of 26 PMHNPs and 363 other NPs. Compared with other NPs, PMHNPs were significantly more likely to work in a telehealth setting (42% vs. 11%, p<0.001), to spend more time working during the initial surge (50% vs. 26%, p<0.05), and to believe that the waiver improved clinical work (52% vs. 25%, p<0.01). Content analysis of PMHNPs' open-ended responses identified four themes: the supervision waiver reduced burden on PMHNPs, collaboration and mentorship models persisted, the pandemic exacerbated the already high demand for psychiatric care, and telehealth helped meet the high demand for such care. CONCLUSIONS: PMHNPs may be more sensitive to the scope-of-practice changes and telehealth expansion than other NPs because of the constraints of the psychiatrist shortage and high relative uptake of telehealth in psychiatric care. The interactions of workforce supply, telehealth expansion, and scope-of-practice laws are important to consider in the development of policies to improve access to mental health care.

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During the COVID-19 pandemic, there was slower growth in the number of new waivers authorizing clinicians to provide buprenorphine treatment for opioid use disorder. However, treatment capacity grew at a stable rate as a result of already authorized clinicians obtaining waivers for larger patient panels. Advanced practice nurses accounted for the largest portion of capacity growth during the pandemic.

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Immune and tissue stem cells retain an epigenetic memory of inflammation that intensifies sensitivity to future encounters. We investigated whether and to what consequence stem cells possess and accumulate memories of diverse experiences. Monitoring a choreographed response to wounds, we found that as hair follicle stem cells leave their niche, migrate to repair damaged epidermis, and take up long-term foreign residence there, they accumulate long-lasting epigenetic memories of each experience, culminating in post-repair epigenetic adaptations that sustain the epidermal transcriptional program and surface barrier. Each memory is distinct, separable, and has its own physiological impact, collectively endowing these stem cells with heightened regenerative ability to heal wounds and broadening their tissue-regenerating tasks relative to their naïve counterparts.

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