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Aims To find how best to integrate religion/spirituality (R/S) into clinical care. Methods This was a qualitative study. 41 mental health patients of varying diagnoses in secondary care underwent semi-structured interviews describing their mental health and spiritual journeys and how these have interacted, before, during and after a period of acute illness. Grounded theory was used. Detailed coding was carried out and themes extracted. Results Preliminary results from this project have already been reported, (submitted for publication). 5 main processes by which R/S interacted positively or negatively with mental health recovery were identified: •R/S experiences, (+ve or -ve), •Existential crisis, (-ve), •Influence of faith community, (+ve or -ve), •Finding a personally meaningful faith, (+ve), •Changing priorities to a more spiritual outlook, (+ve). Further analysis has allowed a comparison between our different participants who were at different stages of recovery: 1.Those who described themselves most as being in recovery tended to have more positive R/S experiences, support from a faith community, a personally meaningful faith and have changed their priorities. Most have also found clinical care helpful. However, often R/S was considered more helpful both for personal recovery and symptom relief. For others in this group, R/S enables living a satisfying life despite limitations of illness partially controlled by medication. 2.Those who described themselves most as struggling with mental illness were much less likely to have a personally meaningful faith or had changed their priorities. They tended to have negative R/S experiences, persistent existential crisis and/or rejection from a faith community. Most of these people find both clinical care and R/S issues unhelpful. Some people were finding clinical care helpful but R/S barriers were blocking their recovery. Many people at all stages of recovery said they wanted more help with R/S issues. They often regard their illness as a spiritual problem and consider positive R/S experiences a key to recovery. Conclusion Spiritual health may be important for recovery from many mental health problems and needs to be addressed according to the 5 themes. •Possible R/S barriers identified, even if symptoms seem to be responding to clinical treatment. •Positive R/S experiences and/or support from a faith community used to help overcome R/S barriers. •Support made available to find a personally meaningful faith and change priorities. •Referral to spiritual care offered more frequently. Clinical care will be most effective if combined with facilitating spiritual health.

IntroductionMedication treatment for opioid use disorder (MOUD) decreases opioid overdose risk and is the standard of care for persons with opioid use disorder (OUD). Recovery coach (RC)-led programs and associated training curriculums to improve outcomes around MOUD are limited. We describe our comprehensive training curriculum including instruction and pedagogy for novel RC-led MOUD linkage and retention programs and report on its feasibility.Methods–pedagogy and training developmentThe Kentucky HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) created the Linkage and Retention RC Programs with a local recovery community organization, Voices of Hope-Lexington. RCs worked to reduce participant barriers to entering or continuing MOUD, destigmatize and educate on MOUD and harm reduction (e.g., safe injection practices), increase recovery capital, and provide opioid overdose education with naloxone distribution (OEND). An extensive hybrid (in-person and online, both synchronous and asynchronous), inclusive learning-focused curriculum to support the programs (e.g., motivational interviewing sessions, role plays, MOUD competency assessment, etc.,) was created to ensure RCs developed the necessary skills and could demonstrate competency before deployment in the field. The curriculum, pedagogy, learning environment, and numbers of RCs trained and community venues receiving a trained RC are reported, along with interviews from three RCs about the training program experience.ResultsThe curriculum provides approximately 150 h of training to RCs. From December 2020 to February 2023, 93 RCs and 16 supervisors completed the training program; two were unable to pass a final competency check. RCs were deployed at 45 agencies in eight Kentucky HCS counties. Most agencies (72%) sustained RC services after the study period ended through other funding sources. RCs interviewed reported that the training helped them better explain and dispel myths around MOUD.ConclusionOur novel training and MOUD programs met a current unmet need for the RC workforce and for community agencies. We were able to train and deploy RCs successfully in these new programs aimed at saving lives through improving MOUD linkage and retention. This paper addresses a need to enhance the training requirements around MOUD for peer support specialists.

Background: In 2021, the Department of Health and Human Services released guidelines allowing waiver-eligible providers seeking to treat up to 30 patients to be exempt from waiver training (WT) and the counseling and other ancillary services (CAS) attestation. This study evaluates if states and the District of Columbia had more restrictive policies preventing adoption of the 2021 federal guidelines. Methods: First, the Westlaw database was searched for buprenorphine regulations. Second, state medical, osteopathic, physician assistant, nursing boards, and single state agencies (SSA) were surveyed to assess for the WT and CAS requirements and if they were discussing the 2021 guidelines. Results were recorded and compared by state and waiver-eligible provider types. Results: The Westlaw search revealed seven states with regulations requiring the WT and ten states requiring CAS. Survey results showed ten state boards/SSAs required WT for at least one waiver-eligible practitioner type and eleven state boards/SSAs required CAS. In some states, the WT and CAS requirements only applied in special circumstances. Eleven states had discrepancies between the Westlaw and survey results among three waiver-eligible provider types. Conclusions: Despite the 2021 federal change intended to increase access to buprenorphine, several states had regulations and/or provider boards and SSAs that were not supportive. Now, the Mainstreaming Addiction Treatment (MAT) Act of 2022 eliminated the federal x-waiver requirement to prescribe buprenorphine. However, these states may continue to have barriers to treatment access despite the MAT Act. Strategies to engage states with these restrictive policies are needed to improve buprenorphine treatment capacity.

Wildfires significantly change boreal forest ecosystem carbon balance through both direct combustion and post-fire carbon dynamics. Affected vegetation influences soil thermal regime and carbon cycling by impacting the surface energy balance of boreal forests. This study uses a process-based biogeochemistry model to quantify carbon budget of North American boreal forests during 1986–2020 based on satellite-derived burn severity data. During the study period, burn severity generally increases. Fires remove ecosystem carbon of 2.4 Pg C and reduce net ecosystem production (NEP) from 32.6 to 0.8 Tg C yr ^−1 , making the forest ecosystems lose 3.5 Pg C, shifting a carbon sink to a source. The canopy’s cooling effect leads to lower soil temperature and lower net primary production due to lower nitrogen mineralization and uptake. Post-fire NEP decreases from 1.6 to 0.8 Tg C yr ^−1 . This reduction accounts for 50% of the simulated NEP when the effects of fire-affected canopy are not considered. Our study highlights the importance of wildfires and their induced-canopy changes in soil thermal and ecosystem carbon dynamics of boreal forests.

Abstract Stem and progenitor cells (SPCs) possess self-remodeling ability and differentiation potential and are responsible for the regeneration and development of organs and tissue systems. However, the precise mechanisms underlying the regulation of SPC biology remain unclear. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) acts on miscellaneous cells via binding to fibroblast growth factor-inducible 14 (Fn14) and exerts pleiotropic functions in the regulation of divergent stem cell fates. TWEAK/Fn14 signaling can regulate the proliferation, differentiation, and migration of multiple SPCs as well as tumorigenesis in certain contexts. Although TWEAK’s roles in modulating multiple SPCs are sparsely reported, the systemic effector functions of this multifaceted protein have not been fully elucidated. In this review, we summarized the fate decisions of TWEAK/Fn14 signaling on multiple stem cells and characterized its potential in stem cell therapy.

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features—intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS.

Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success. Here we demonstrate approaches to interrogate patient-level molecular variance in a chronic skin inflammatory disease, psoriasis vulgaris, leveraging single-cell RNA-sequencing of CD45+ cells isolated from active lesions. Highly psoriasis-specific transcriptional abnormalities display greater than average inter-individual variance, nominating them as potential sources of clinical heterogeneity. We find that one of these chemokines, CXCL13, demonstrates significant correlation with severity of lesions within our patient series. Our analyses also establish that genes elevated in psoriatic skin-resident memory T cells are enriched for programs orchestrating chromatin and CDC42-dependent cytoskeleton remodeling, specific components of which are distinctly correlated with and against Th17 identity on a single-cell level. Collectively, these analyses describe systematic means to dissect cell type- and patient-level differences in cutaneous psoriasis using high-resolution transcriptional profiles of human inflammatory disease.

Purpose: Immunization rates in many cities in the United States remain suboptimal compared to Healthy People 2020 Goals and are lower than national averages. This study aimed to determine whether a lecture-based educational intervention targeted at nurses and medical assistants would improve vaccination rates. Methods: We conducted a quality improvement study in two urban academic family medicine clinics serving a predominantly Medicaid patient population as well as a sizable proportion of refugees. The intervention consisted of 3 lectures that were delivered to clinic nurses and medical assistants. Vaccinations in 1689 patients — 872 in the 3-month preintervention period, 817 in the 3-month postintervention period — were analyzed. Results: Following the educational intervention, a statistically significant increase was seen only in human papillomavirus vaccine immunization rates for 13–18-year-olds (from 90.7% [n = 54] to 100% [n = 45]; P = 0.036). When the results were stratified by clinic, only 1 site showed statistically significant increases in: pneumococcal polysaccharide vaccine (23-valent) for high-risk 19-to-64-year-olds (from 36.4% [n = 154] to 47.8% [n = 136]; P = 0.049); Haemophilus influenzae type B vaccine for 2-month-to-5-year-olds (from 91.1% [n = 112] to 97.3% [n = 111]; P = 0.048); and meningococcal conjugate vaccine (quadrivalent) for 13–18-year olds (from 85.2% [n = 27] to 100% [n = 26]; P = 0.042). No increases were seen for our study’s refugee patient population (n = 171), and a significant decrease of the second-dose measles, mumps, and rubella vaccine (P = 0.036) occurred in this subcohort. Conclusions: Ultimately, this quality improvement study demonstrated that educational interventions alone have a limited impact on increasing immunization rates.

Vasoplegic syndrome, a possible complication of cardiopulmonary bypass, is a critical state of unregulated systemic vasodilation with decreased vascular resistance and a pathological insensitivity to conventional inotropes and vasoconstrictors. This case demonstrates the use of methylene blue and hydroxocobalamin as medications in the treatment of refractory vasoplegic syndrome in the context of cardiac surgery due to their differences in mechanism of action. A 24-year-old female with history of intravenous drug abuse and hepatitis C infection underwent mitral valve repair for infective endocarditis. Preoperative transesophageal echocardiography showed normal right ventricular function, left ventricular ejection fraction of 65%–75%, and severe mitral regurgitation with vegetation. In order to maintain a mean arterial pressure over 60 mmHg during cardiopulmonary bypass, norepinephrine, epinephrine, and vasopressin infusions were required. Given the patient’s minimal response to these medications, a 1.5 mg/kg bolus of intravenous methylene blue was also given intraoperatively; vasoplegic syndrome remained refractory in the post-cardiopulmonary bypass period. A 5 g dose of intravenous hydroxocobalamin was administered in the intensive care unit postoperatively. Postoperative liver function tests were abnormal, and post-cardiopulmonary bypass transesophageal echocardiography revealed mildly decreased right ventricular function. While in the intensive care unit, the patient was placed on venoarterial extracorporeal membrane oxygenation and underwent therapeutic plasma exchange. Vasopressors were weaned over the course of the next 24 h. The patient was able to be transferred out of the intensive care unit on postoperative day 5. Traditional vasoconstrictors activate signal transduction pathways that lead to myosin phosphorylation. Vasodilatory molecules such as nitric oxide (NO) activate the enzyme soluble guanylyl cyclase (sGC), ultimately leading to the dephosphorylation of myosin. Nitric Oxide Synthase (NOS) can potentially increase NO levels 1000-fold when activated by inflammatory cytokines. Methylene blue is a direct inhibitor of NOS. It also binds and inhibits sGC. Hydroxocobalamin is a direct inhibitor of NO, likely inhibits NOS and may also act through additional mechanisms.

Summary: Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.

Background As younger patients are being considered for transcatheter aortic valve implantation (TAVI), the assessment and treatment of concomitant coronary artery disease is taking on increased importance. Methods and Results Thirteen contemporary lower‐risk patients with TAVI with severe aortic stenosis (AS) and moderate‐severe coronary lesions were included. Patients underwent assessment of coronary hemodynamics in the presence of severe AS (pre‐TAVI), in the absence of severe AS (immediately post‐TAVI), and at longer‐term follow‐up (6 months post‐TAVI). Fractional flow reserve decreased from 0.85 (0.76–0.88) pre‐TAVI to 0.79 (0.74–0.83) post‐TAVI, and then to 0.71 (0.65–0.77) at 6‐month follow‐up (P

Multiple locus sequence typing (MLST) has become a central genotyping strategy for analysis of bacterial populations. The scheme involves de novo sequencing of 6-8 housekeeping loci to assign unique sequence types. In this work we adapted MLST to a rapid microfluidics platform in order to enhance speed and reduce laboratory labor time.Using two integrated microfluidic devices, DNA was purified from 100 Bacillus cereus soil isolates, used as a template for multiplex amplification of 7 loci and sequenced on forward and reverse strands. The time on instrument from loading genomic DNA to generation of electropherograms was only 1.5 hours. We obtained full-length sequence of all seven MLST alleles from 84 representing 46 different Sequence Types. At least one allele could be sequenced from a further 15 strains. The nucleotide diversity of B. cereus isolated in this study from one location in Rockville, Maryland (0.04 substitutions per site) was found to be as great as the global collection of isolates.Biogeographical investigation of pathogens is only one of a panoply of possible applications of microfluidics based MLST; others include microbiologic forensics, biothreat identification, and rapid characterization of human clinical samples.