Id genes are essential for early heart formation.

Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix-loop-helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation-Tcf3 and Foxa2-and activating inducers Evx1, Grrp1, and Mesp1. Most importantly, CRISPR/Cas9-mediated ablation of the entire Id (Id1-4) family in mouse embryos leads to failure of anterior cardiac progenitor specification and the development of heartless embryos. Thus, Id proteins play a central and evolutionarily conserved role during heart formation and provide a novel means to efficiently produce cardiovascular progenitors for regenerative medicine and drug discovery applications.

Eliminate the buprenorphine DEA X waiver: Justification using a policy analysis approach.

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.

A Pragmatic, Person-Centered View of Cannabis in the United States: Pursuing Care That Transcends Beliefs.

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.

Influences on advance practice nursing education to prescribe medications for opioid use disorder.

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.

Reducing Drug Overdose Deaths: Significant Changes Needed in U.S. Drug Treatment Policy.

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.].

"The Future of Nursing: Accelerating gains made to address the continuum of substance use".

PURPOSE: Guided by four key messages from the decade-old Institute of Medicine (IOM) report, "The Future of Nursing," this paper highlights the progress made by the nursing profession in addressing substance use and its related disorders and offers recommendations to sustain and advance efforts to enhance care for persons who use substances, one of the most stigmatized and vulnerable populations. RESULTS: Patterns of substance use have shifted over the past 10 years, but the associated harms remain consequential. As awareness of the continuum of substance use has expanded, the care of persons with substance use has also expanded, from the domains of psychiatric-mental health and addictions nursing specialties to the mainstream of nursing. Now, greater efforts are being undertaken to identify and intervene with persons at risk for and experiencing substance use disorders. Nurses have advanced the knowledge and skills necessary for substance-related nursing care including education and training, leadership, care innovations, and workforce expansion and can drive efforts to increase public knowledge about the health risks associated with substance use. Recommendations aligned with each of the four IOM key messages are offered. CONCLUSIONS: As a profession, nursing has a responsibility to expand the progress made in addressing substance use - from prevention and early intervention to tertiary care. Nurses at all levels of education and practice are in key positions to carry out the recommendations herein to accelerate the changes needed to provide high quality care for persons impacted by substance use.

Identifying Amidyl Radicals for Intermolecular C-H Functionalizations.

Recent studies have demonstrated the capabilities of amidyl radicals to facilitate a range of intermolecular functionalizations of unactivated, aliphatic C-H bonds. Relatively little information is known regarding the important structural and electronic features of amidyl and related radicals that impart efficient reactivity. Herein, we evaluate a diverse range of nitrogen-centered radicals in unactivated, aliphatic C-H chlorinations. These studies establish the salient features of nitrogen-centered radicals critical to these reactions in order to expedite the future development of new site-selective, intermolecular C-H functionalizations.

Two Different Buprenorphine Treatment Settings With Similar Retention Rates: Implications for Expanding Access to Treatment for Opioid Use Disorder.

INTRODUCTION: There is considerable need for effective and accessible treatment for opioid use disorder. AIMS: Our study explored differences in buprenorphine treatment retention and duration, with a focus on selected sociodemographic factors and treatment indicators, in two different settings: an office-based buprenorphine induction and stabilization clinic (OBIC) and a community-based primary care clinic (CPC). METHOD: This nonexperimental retrospective chart review compared demographic information and buprenorphine treatment details, including treatment retention and duration. RESULTS: There were no statistically significant differences in buprenorphine treatment indicators between the OBIC and CPC groups, with two exceptions: the number of written buprenorphine prescriptions was significantly greater for the OBIC group, as was the number of filled buprenorphine prescriptions. CONCLUSIONS: Given similar treatment retention and duration in two different buprenorphine treatment settings, our findings suggest that access to buprenorphine treatment in standard integrated care settings can be supplemented by novel treatment structures such as the OBIC in order to increase access to care during the current opioid epidemic.

Innervation of dystrophic muscle after muscle stem cell therapy.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is caused by loss of the structural protein, dystrophin, resulting in muscle fragility. Muscle stem cell (MuSC) transplantation is a potential therapy for DMD. It is unknown whether donor-derived muscle fibers are structurally innervated. METHODS: Green fluorescent protein (GFP)-expressing MuSCs were transplanted into the tibials anterior of adult dystrophic mdx/mTR mice. Three weeks later the neuromuscular junction was labeled by immunohistochemistry. RESULTS: The percent overlap between pre- and postsynaptic immunolabeling was greater in donor-derived GFP(+) myofibers, and fewer GFP(+) myofibers were identified as denervated compared with control GFP(-) fibers (P = 0.001 and 0.03). GFP(+) fibers also demonstrated acetylcholine receptor fragmentation and expanded endplate area, indicators of muscle reinnervation (P = 0.008 and 0.033). CONCLUSION: It is unclear whether GFP(+) fibers are a result of de novo synthesis or fusion with damaged endogenous fibers. Either way, donor-derived fibers demonstrate clear histological innervation. Muscle Nerve 54: 763-768, 2016.

Visible-light-mediated, nitrogen-centered radical amination of tertiary alkyl halides under metal-free conditions to form α-tertiary amines.

A mild and operationally convenient amino-functionalization of a range of tertiary alkyl halides by reaction with iminoiodinanes (PhI[double bond, length as m-dash]NNs) and I2 has been developed. According to the mechanistic experiments described within, the reaction is speculated to proceed through a light-promoted, N-centered radical pathway involving a N,N-diiodosulfonamide reactive species. This method of direct N-incorporation offers an attractive alternative to the production of α-tertiary amines, a synthetically challenging structural class found in a variety of bioactive molecules.

Perspectives on APRN prescribing of medications for opioid use disorder: Key barriers remain.

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.

Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices.

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.