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Abstract Background Youth involved in the legal system have disproportionately higher rates of problematic substance use than non-involved youth. Identifying and connecting legal-involved youth to substance use intervention is critical and relies on the connection between legal and behavioral health agencies, which may be facilitated by learning health systems (LHS). We analyzed the impact of an LHS intervention on youth legal and behavioral health personnel ratings of their cross-system collaboration. We also examined organizational climate toward evidence-based practice (EBP) over and above the LHS intervention. Methods Data were derived from a type II hybrid effectiveness trial implementing an LHS intervention with youth legal and community mental health centers (CMHCs) in eight Indiana counties. Using a stepped wedge design, counties were randomly assigned to one of three cohorts and stepped in at nine-month intervals. Counties were in the treatment phase for 18 months, after which they were in the maintenance phase. Youth legal system and CMHC personnel completed five waves of data collection (n=307 total respondents, ranging from 108-178 per wave). Cross-system collaboration was measured via the Cultural Exchange Inventory, organizational EBP climate via the Implementation Climate Scale and Implementation Citizenship Behavior Scale, and intervention via a dummy-coded indicator variable. We conducted linear mixed models to examine: 1) the treatment indicator, and 2) the treatment indicator and organizational EBP climate variables on cross-system collaboration. Results The treatment indicator was not significantly associated with cross-system collaboration. When including the organizational EBP climate variables, the treatment indicator significantly predicted cross-system collaboration. Compared to the control phase, treatment (B=0.41, standard error [SE]=0.20) and maintenance (B=0.60, SE=0.29) phases were associated with greater cross-system collaboration output. Conclusions The analysis may have been underpowered to detect an effect; third variables may have explained variance in cross-system collaboration, and, thus, the inclusion of important covariates may have reduced residual errors and increased the estimation precision. The LHS intervention may have affected cross-system collaboration perception and offers a promising avenue of research to determine how systems work together to improve legal-involved-youth substance use outcomes. Future research is needed to replicate results among a larger sample and examine youth-level outcomes. Trial registration Clinicaltrials.gov identifier: NCT04499079. Registered 30 July 2020. https://clinicaltrials.gov/study/NCT04499079 .

Abstract Background Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may be partly attributable to attitudes about and training in MOUDs among youth-serving professionals. We extended prior research by conducting descriptive analyses of attitudes regarding effectiveness and acceptability of MOUDs, as well as training in MOUDs, among youth legal system (YLS) employees and community mental health center (CMHC) personnel who interface professionally with youth. Methods Using survey data from participants (n = 181) recruited from eight Midwest counties, we examined: (1) differences in MOUD attitudes/training by MOUD type and (2) by respondent demographics, and (3) prediction of MOUD attitudes/training by participant-reported initiatives to implement evidence-based practices (EBPs), workplace culture around EBPs, and workplace stress. Attitudes and training were measured in reference to five MOUD types (methadone, oral buprenorphine, injectable buprenorphine, oral naltrexone, injectable naltrexone) on three subscales (effectiveness, acceptability, training). Results Wilcoxon signed-rank tests demonstrated that most outcomes differed significantly by MOUD type (differences observed among 22 of 30 tests). Kruskal-Wallis tests suggested MOUD differences based on demographics. For methadone, CMHC providers endorsed greater perceived effectiveness than YLS providers and age explained significant differences in perceived effectiveness. For buprenorphine, CHMC providers viewed oral or injectable buprenorphine as more effective than YLS employees, respondents from more rural counties viewed oral buprenorphine as more effective than those from less rural counties, and age explained differences in perceived effectiveness. For naltrexone, perceived gender differed by gender. Hierarchical ordinal logistic regression analysis did not find an association between personal initiatives to implement EBPs, workplace culture supporting EBPs, or workplace stress and effectiveness or acceptability of MOUDs. However, personal initiatives to implement EBPs was associated with training in each MOUD. Conclusions These results highlight a few key findings: effectiveness/acceptability of and training in MOUDs largely differ by MOUD type; setting, rurality, age, gender, and education explain group differences in perceived effectiveness of and training in MOUDs; and implementing EBPs is associated with training in MOUDs. Future research would benefit from examining what predicts change in MOUD attitudes longitudinally.

Aims & Objectives The purpose of this study was to identify patient characteristics associated with engagement and completion of physical therapy (PT) following total knee arthroplasty (TKA) and examine the relationship between number of PT sessions attended and outcomes during the first 12 weeks after surgery. Methods Patients underwent unilateral primary TKA by a single surgeon and were advised to complete 17 PT sessions over 6 weeks at a hospital-affiliated facility. Analyses examined predictors of PT engagement (attendance of ≥2 sessions) and completion (attendance of 17 ± 1 sessions) within 6 weeks and associations between number of PT sessions attended and changes in range of motion (ROM) and Knee Injury and Osteoarthritis Outcome Score (KOOS) values. Results Patients living

Purpose This study delineates a number of Medicaid youth with tobacco use disorder (TUD), prescribing habits for treatment, and associated externalizing disorders. Methods Youth Medicaid claims from 2007-2017 processed in a large Midwestern city were analyzed for a diagnosis of TUD, related pharmacotherapy, and externalizing mental health and substance use disorders. Results Claims connected 6541 patients with 42 890 visits. Mean age was 16.4 with 40% female. 1232 of the 6541 charts contained a TUD diagnosis equating to 1848 visits. A comorbid diagnosis of ADHD, cannabis use, and conduct disorder were more common in males (3.9% vs 1.3% in females; 3.4% vs .8%; and 2.8% vs .8%; P < .05). 808 scripts were provided to 152 of the 1232 youths, with 4.7% of those scripts a nicotine replacement product. Conclusions Pharmacotherapy is underutilized in this Medicaid claims data set. Certain externalizing factors were associated with males with TUD more than females.

Abstract Background While COVID-19 has had far-reaching consequences on society and health care providers, there is a paucity of research exploring frontline emergency medicine (EM) provider wellness over the course of a pandemic. The objective of this study was to assess the well-being, resilience, burnout, and wellness factors and needs of EM physicians and advanced practice providers (e.g., nurse practitioners and physician assistants; APPs) during the initial phase of the COVID-19 pandemic. Methods A descriptive, prospective, cohort survey study of EM physicians and APPs was performed across ten emergency departments in a single state, including academic and community settings. Participants were recruited via email to complete four weekly, voluntary, anonymous questionnaires comprised of customized and validated tools for assessing wellness (Well Being Index), burnout (Physician Work Life Study item), and resilience (Brief Resilience Scale) during the initial acceleration phase of COVID-19. Univariate and multivariate analysis with Chi-squared, Fisher’s Exact, and logistic regression was performed. Results Of 213 eligible participants, response rates ranged from 31 to 53% over four weeks. Women comprised 54 to 60% of responses. Nonrespondent characteristics were similar to respondents. Concern for personal safety decreased from 85 to 61% (p 50% of respondents initially without significant change (p = 0.05 and p = 0.30 respectively). Women were nearly twice as likely to report feelings of isolation as men (OR 1.95; 95% CI 1.82–5.88). Working part-time carried twice the risk of burnout (OR, 2.45; 95% CI, 1.10–5.47). Baseline resilience was normal to high. Provider well-being improved over the four weeks (30 to 14%; p = 0.01), but burnout did not significantly change (30 to 22%; p = 0.39). Conclusion This survey of frontline EM providers, including physicians and APPs, during the initial surge of COVID-19 found that despite being a resilient group, the majority experienced stress, anxiety, fear, and concerns about personal safety due to COVID-19, putting many at risk for burnout. The sustained impact of the pandemic on EM provider wellness deserves further investigation to guide targeted interventions.

While archaeal proteomics advanced rapidly, a comprehensive proteome database for archaea is lacking. Therefore, the authors here launch the Archaeal Proteome Project, a community-effort providing insights into archaeal cell biology via the combined reanalysis of Haloferax volcanii proteomics data.

BackgroundTreating substance use disorders (SUDs) during adolescence can prevent adult addiction and improve youth outcomes. However, it can be challenging to keep adolescents with SUDs engaged in ongoing services, thus limiting potential benefits. Developmentally appropriate tools are needed to improve treatment engagement during and between sessions for youth with SUDs and mental health disorders. Mobile health apps may augment or replace psychotherapy components; however, few have been developed specifically for youth with SUDs following user-guided design principles, which may limit their appropriateness and utility. Formative research on acceptability to intended end users is needed before the efficacy of such tools can be examined. ObjectiveThis study involves user-centered, iterative development and initial user testing of a web-based app for adolescents with SUDs and mental health concerns. MethodsAdolescents aged 14 to 17 years with past-year involvement in outpatient psychotherapy and behavioral health clinicians with adolescent SUD treatment caseloads were recruited. Across 2 assessment phases, 40 participants (alpha: 10 youths and 10 clinicians; beta: 10 youths and 10 clinicians) viewed an app demonstration and completed semistructured interviews and questionnaires about app content and functionality. ResultsParticipants expressed positive impressions of the app and its potential utility in augmenting outpatient therapy for youth with SUDs and mental health concerns. Noted strengths included valuable educational content, useful embedded resources, and a variety of activities. Adolescents and clinicians favored the app over conventional (paper-and-pencil) modalities, citing convenience and familiarity. The app was found to be user-friendly and likely to improve treatment engagement. Adolescents suggested the inclusion of privacy settings, and clinicians recommended more detailed instructions and simplified language. ConclusionsThe novel app developed here appears to be a promising, acceptable, and highly scalable resource to support adolescents with SUDs and mental health concerns. Future studies should test the efficacy of such apps in enhancing adolescent behavioral health treatment engagement and outcomes.

Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival.

The ubiquitin-like (Ubl) protein is widely distributed in Archaea and involved in many cellular pathways. A well-established method to reconstitute archaeal Ubl protein conjugation in vitro is important to better understand the process of archaeal Ubl protein modification. This protocol describes the in vitro reconstitution of Ubl protein modification and following analysis of this modification in Haloferax volcanii, a halophilic archaeon serving as the model organism.

ABSTRACT Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme found in all domains of life that catalyzes the reduction of methionine-S-sulfoxide (MSO) to methionine in proteins and free amino acids. We demonstrate that archaeal MsrA has a ubiquitin-like (Ubl) protein modification activity that is distinct from its stereospecific reduction of MSO residues. MsrA catalyzes this Ubl modification activity, with the Ubl-activating E1 UbaA, in the presence of the mild oxidant dimethyl sulfoxide (DMSO) and in the absence of reductant. In contrast, the MSO reductase activity of MsrA is inhibited by DMSO and requires reductant. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis reveals that MsrA-dependent Ubl conjugates are associated with DNA replication, protein remodeling, and oxidative stress and include the Ubl-modified MsrA, Orc3 (Orc1/Cdc6), and Cdc48d (Cdc48/p97 AAA+ ATPase). Overall, we found archaeal MsrA to have opposing MSO reductase and Ubl modifying activities that are associated with oxidative stress responses and controlled by exposure to mild oxidant. IMPORTANCE Proteins that are damaged by oxidative stress are often targeted for proteolysis by the ubiquitin-proteasome system (UPS). The mechanisms that control this response are poorly understood, especially under conditions of mild oxidative stress when protein damage is modest. Here, we discovered a novel function of archaeal MsrA in guiding the Ubl modification of target proteins in the presence of mild oxidant. This newly reported activity of MsrA is distinct from its stereospecific reduction of methionine-S-sulfoxide to methionine residues. Our results are significant steps forward, first, in elucidating a protein factor that guides Ubl modification in archaea, and second, in providing an insight into oxidative stress responses that can trigger Ubl modification in a cell.

Background and Aims: Although opposing risk factors have been proposed for mate kirikōpū/endometriosis (oestrogen-dependence) and huahua hua kūao/polycystic ovary syndrome (PCOS; androgen dependence), there is a cohort of individuals with both endometriosis and PCOS. We propose that disease comorbidity will alter symptom profiles in comparison to those with only one disease, and that analysis of these differential profiles may hint at underlying mechanisms of disease pathology. Methods: An anonymous online survey was distributed via social media (NZ residents, >18 years) and included questions related to diagnosis, symptoms, treatment and management of endometriosis and/or PCOS. Results: In total, 1323 responses (median [range] = 31 years [18–72]) were received within a two-week period (endometriosis only: n=615, 48%; PCOS only: n=459, 35%; both diseases: n=247, 19%). When asked about symptoms ‘ever experienced’, comorbid individuals report both symptoms commonly ascribed to endometriosis (e.g, dysmenorrhea) as well as those ascribed to PCOS (e.g., irregular periods) thereby exacerbating impacts on quality of life. An exception, the proportion of individuals reporting absent menstrual periods was increased in cormobid individuals (45%) relative to those with endometriosis only (21%), but decreased relative to those with PCOS only (67%), suggesting a more complex interaction between the two diseases. Conclusions: These data highlight the heterogenity of disease phenotype in individuals with endometriosis and/or PCOS. We suggest that an understanding of the intersection of these two common diseases, and a recognition of the associated phenotypic diversity, will provide avenues of research to better understand the pathophysiology of both endometriosis and PCOS.