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Jeremy D Kidd,1,2 Jennifer L Smith,1 Mei-Chen Hu,1 Eva M Turrigiano,2 Adam Bisaga,1,2 Edward V Nunes,1,2 Frances R Levin1,2 1Department of Psychiatry, Columbia University, New York, NY, USA; 2Division on Substance Use Disorders, New York State Psychiatric Institute, New York, NY, USACorrespondence: Jeremy D Kidd Email Jeremy.Kidd@nyspi.columbia.eduPurpose: Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based framework for assessing and addressing risky substance use. This study evaluated the substance-related attitudes of medical students who participated in an Enhanced Pre-Clinical SBIRT Curriculum designed to reduce stigma, help students empathize with the experiences of people using alcohol and drugs, understand substance use in-context, and feel more optimistic about efforts to prevent and treat substance use disorders (SUDs).Methods: Students (N=118; 73.8% of eligible) completed the Attitudes and Opinions Survey for alcohol and drugs before and after this 2-year, multi-modality curriculum. The authors classified attitudes as “positive” or “negative” and grouped students by pre-post attitudinal change: persistently negative, persistently positive, negative-to-positive, positive-to-negative. Using chi-square tests, the authors assessed differences by sex, race/ethnicity, and whether students had a family member or friend with an SUD.Results: Most students (> 90%) reported persistently positive attitudes regarding physicians in recovery, societal contributions of patients with SUDs; ability to learn from such patients; and general attitudes toward SUD treatment. This skewed distribution precluded the investigation of subgroup differences. Fewer students reported persistently positive attitudes regarding SUD patients’ healthcare utilization (alcohol 58.5%; drug 57.8%) and impact on other patients’ care (alcohol 73.7%; drug 72.4%), compared to other attitudinal domains (at p-values < 0.0001 in the McNemar’s tests). Approximately, 1 in 5 students reported more negative healthcare utilization attitudes on follow-up. There were no demographic differences in these two attitudinal domains.Conclusion: Unlike previous studies of medical student attitudes, most students who participated in the Enhanced Pre-Clinical SBIRT Curriculum reported an enduring appreciation for the educational and societal contributions of patients with SUDs. Attitudes toward healthcare utilization and the impact of patients with SUDs on the care of other patients were more resistant to change, possibly due to the predominance of acute-care inpatient settings in clinical training.Keywords: addiction, alcohol, drugs, screening, brief intervention, medical education

© 2014 Vieira et al.Treatment options for people living with amyotrophic lateral sclerosis (ALS) are limited and ineffective. Recently, dexpramipexole (RPPX) was advanced into human ALS clinical trials. In the current studies, we investigated RPPX in two p

Amyotrophic lateral sclerosis (ALS) has been linked to overactivity of the protein kinase RNA-like ER kinase (PERK) branch of the unfolded protein response (UPR) pathway, both in ALS patients and mouse models. However, attempts to pharmacologically modulate PERK for therapeutic benefit have yielded inconsistent and often conflicting results. This study sought to address these discrepancies by comprehensively evaluating three commonly used, CNS-penetrant, PERK modulators (GSK2606414, salubrinal, and Sephin1) in the same experimental models, with the goal of assessing the viability of targeting the PERK pathway as a therapeutic strategy for ALS. To achieve this goal, a tunicamycin-challenge assay was developed using wild-type mice to monitor changes in liver UPR gene expression in response to PERK pathway modulation. Subsequently, multiple dosing regimens of each PERK modulator were tested in standardized, well-powered, gender-matched, and litter-matched survival efficacy studies using the SOD1G93A mouse model of ALS. The alpha-2-adrenergic receptor agonist clonidine was also tested to elucidate the results obtained from the Sephin1, and of the previously reported guanabenz studies, by comparing the effects of presence or absence of α-2 agonism. The results revealed that targeting PERK may not be an ideal approach for ALS treatment. Inhibiting PERK with GSK2606414 or activating it with salubrinal did not confer therapeutic benefits. While Sephin1 showed some promising therapeutic effects, it appears that these outcomes were mediated through PERK-independent mechanisms. Clonidine also produced some favorable therapeutic effects, which were unexpected and not linked to the UPR. In conclusion, this study highlights the challenges of pharmacologically targeting PERK for therapeutic purposes in the SOD1G93A mouse model and suggests that exploring other targets within, and outside, the UPR may be more promising avenues for ALS treatment., Competing Interests: We would like to disclose that ALS TDI has been granted a patent for small molecules analogs of salubrinal. However, we have no financial or personal relationships with any organization or individual that could influence the content or conclusions presented in this manuscript., (Copyright: © 2024 Vieira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Methamphetamine use disorder (MethUD) disproportionately affects men who have sex exclusively with men or with men and women (collectively MSM/W), compared to men who have sex with women (MSW). This study is the first MethUD medication trial to compare treatment effect for these groups, hypothesizing that extended-release injectable naltrexone 380mg every 3 weeks plus oral extended-release bupropion 450mg daily would be less effective for MSM/W than MSW., Methods: Data come from men (N = 246) in a multi-site, double-blind, randomized, placebo-controlled trial with sequential parallel comparison design. In Stage 1 (6-weeks), participants were randomized to active treatment or placebo. In Stage 2 (6-weeks), Stage 1 placebo non-responders were rerandomized. Treatment response was ≥3 methamphetamine-negative urine samples, out of four obtained at the end of Stages 1 and 2. Treatment effect was the active-versus-placebo between-group difference in the weighted average Stages 1 and 2 responses., Results: MSM/W (n = 151) were more likely than MSW (n = 95) to be Hispanic, college-educated, and living with HIV. Adjusting for demographics, among MSM/W, response rates were 13.95 % (active treatment) and 2.78 % (placebo) in Stage 1; 23.26 % (active treatment) and 4.26 % (placebo) in Stage 2. Among MSW, response rates were 7.69 % (active treatment) and 5.80 % (placebo) in Stage 1; 3.57 % (active treatment) and 0 % (placebo) in Stage 2. Treatment effect was significantly larger for MSM/W (h = 0.1479) than MSW (h = 0.0227) (p = 0.04)., Conclusions: Findings suggest efficacy of extended-release naltrexone plus bupropion for MSM/W, a population heavily burdened by MethUD. While a secondary outcome, this intriguing finding merits testing in prospective trials., Competing Interests: Declaration of Competing Interest Drs. Kidd and Smiley reports no financial relationships with commercial interests. Dr. Coffin directs an NIH-funded trial that receives donated tenofovir-emtricitabine from Gilead Sciences. Dr. Carmody has been a consultant for Alkermes. Dr. Levin receives grant support from the NIDA, SAMHSA, US World Meds and research support from Aelis Pharmaceuticals. She also receives medication from Indivior for research. In addition, Dr. Levin served as a nonpaid member of a Scientific Advisory Board for Alkermes, Indivior, Novartis, Teva, and US WorldMeds; receives royalties from APA Publishing; and is a consultant to Major League Baseball. Dr. Nunes has served as an uncompensated consultant to Alkermes, Indivior, and Camurus, and as an investigator on NIH-funded studies that received in-kind medication from Alkermes, Indivior, and Braeburn/Camurus, and in-kind digital therapeutics from Pear Therapeutics and Chess Health. Dr. Shoptaw receives clinical support for his research from Gilead Sciences, Alkermes and Indivior. He also consults with Aelis Pharmaceuticals. Dr. Shoptaw is also the Editor-in-Chief at Drug and Alcohol Dependence, an Elsevier journal., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Transgender individuals experience numerous health disparities relative to cisgender individuals. However, most transgender-health studies have focused on convenience samples with limited generalizability. This study utilized data from the 2016-2018 TransPop Study, the first national probability sample of transgender adults (n=274) with a cisgender comparison sample (n=1162). Using multivariable logistic regression, adjusted for demographics, we compared the prevalence of hazardous drinking, problematic drug use, serious psychological distress, suicidality, and non-suicidal self-injury between transgender and cisgender individuals and among transgender men (n=78), transgender women (n=120), and transgender nonbinary individuals (n=76). Among transgender individuals, 28.2% (95%CI 21.2-35.2) and 31.2% (95%CI 23.8-38.7) reported hazardous drinking and problematic drug use, respectively; 44.4% (95% CI 35.8-53.0) reported recent suicidal ideation, 6.9% (95% CI 2.3-11.5) reported a recent suicide attempt, and 21.4% (95% CI 14.5%-28.4%) reported recent non-suicidal self-injury. In their lifetime, 81.3% (95%CI 75.1-87.5) of transgender respondents had suicidal ideation, 42.0% (95%CI 34.2-49.8) had attempted suicide, and 56.0% (95% CI 48.2-63.8) reported non-suicidal self-injury. Most (81.5%; 95%CI 75.5-87.5) had utilized formal mental health care and 25.5% (95%CI 18.5-32.4) had sought informal mental health support. There were no differences in alcohol or drug-use outcomes between transgender and cisgender adults. Compared to cisgender adults, transgender adults had higher odds of serious psychological distress (aOR=3.1; 95%CI 1.7-5.7), suicidal ideation (recent: aOR=5.1, 95%CI 2.7-9.6); lifetime: aOR=6.7, 95%CI 3.8-11.7), lifetime suicide attempts (aOR=4.4, 95%CI 2.4-8.0), and non-suicidal self-injury (recent: aOR=13.0, 95%CI 4.8-35.1); lifetime: aOR=7.6, 95%CI 4.1-14.3). Transgender nonbinary adults had the highest odds for all outcomes, including substance use outcomes. Findings from these national probability samples support those of earlier convenience-sample studies showing mental health disparities among transgender adults relative to cisgender adults, with nonbinary individuals at highest risk. These findings also highlight variations in risk across sub-groups of transgender individuals., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Background: Transgender and nonbinary (TGNB) populations experience high rates of hazardous drinking (HD) and alcohol use disorder (AUD) as well as unique treatment barriers. This is due, in-part, to discrimination and stigma within and outside of the healthcare system. Cultural adaptation of clinical interventions can improve outcomes for marginalized populations, but no such adapted interventions exist for AUD among TGNB individuals. This study sought to understand how TGNB individuals perceive currently available AUD psychotherapies and to generate knowledge about potential areas for cultural adaptation., Methods: As part of a qualitative study of HD among TGNB individuals (N=27), participants were asked to imagine that they were clients in psychotherapy vignettes corresponding to cognitive behavioral therapy, motivational enhancement therapy, and twelve step facilitation. Interviews were audio-recorded and professionally transcribed. A coding team used an iterative codebook to guide coding. Categories emerged from this process that reflected participants' perceptions and allowed for the identification of potential cultural-adaptation targets., Results: Across all three psychotherapies, participants wanted therapists to explicitly discuss gender identity and culturally salient HD risk factors for TGNB individuals (e.g., discrimination, stigma, gender dysphoria). There were also modality-specific recommendations to incorporate principles of trauma-informed care into cognitive behavioral therapy, avoid motivational enhancement therapy exercises that oversimplify decision-making, and recognize that the twelve-step-facilitation concept of "powerlessness" may conflict with how many TGNB people see themselves., Conclusions: These findings highlight areas for cultural adaptation that can be evaluated in future intervention trials in an effort to improve psychotherapy acceptability and efficacy for TGNB individuals., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Research on opioid misuse, opioid use disorder (OUD), and overdose (i.e., opioid outcomes) among lesbian, gay, bisexual, transgender, queer, and other populations within the LGBTQ umbrella (LGBTQ+) remains sparse. The purpose of this scoping review was to characterize the state of the research on opioid outcomes among LGBTQ+ populations, and identify gaps in the extant literature and areas for future research. Methods: We conducted a scoping review of peer-reviewed, English language articles published between 2011 and 2020 that examined opioid outcomes among LGBTQ+ populations in the CINAHL, Embase, PubMed, and PsycINFO databases. We extracted data from articles that focused on opioid outcomes within their specific aims or purpose. We include a general summary for articles that secondarily described opioid outcomes among LGBTQ+ populations. Results: Of 113 published studies that examined opioid outcomes among LGBTQ+ populations, 10% ( n  = 11) were specifically designed to focus on this topic. Across studies, bisexual populations, particularly women, were at highest risk for opioid misuse and OUD. Few studies examined opioid outcomes by more than one dimension of sexual orientation ( n  = 3, 27%), race and/or ethnicity ( n  = 3, 27%), or age ( n  = 5, 45%). Only two included transgender or gender diverse samples; only one explicitly measured gender identity. Conclusions: Future research is needed to understand the impact of the opioid epidemic on LGBTQ+ people, particularly transgender and other gender diverse individuals, and the intersectional role of race, ethnicity, and age in opioid disparities among LGBTQ+ individuals. Additional research could contribute to the development of much-needed affirming OUD treatment and other services for LGBTQ+ people.

Objective: Transgender and nonbinary (TGNB) individuals are a health disparity population at high risk for sleep disturbance (e.g., insomnia). Recent evidence suggests minority stress (e.g., discrimination) is associated with sleep disturbance in TGNB adults. However, investigators have yet to identify factors that might explain this relationship. In this study, we investigated the role of problematic drug use (PDU) in the relationship between discrimination and sleep disturbance in TGNB individuals., Methods: The study sample included 194 TGNB participants from Wave 5 (2021) of Project AFFIRM, a multi-site longitudinal study of transgender health. Discrimination, PDU, and sleep disturbance were measured using the Everyday Discrimination Scale, Drug Use Disorders Identification Test (DUDIT), and PROMIS Sleep Disturbance measures, respectively. Individuals were classified as having PDU using established DUDIT criteria that were applied based on sex assigned at birth. Regression analyses were used to estimate the associations of study variables, and subsequently, mediation analysis was used to determine whether PDU partially mediated the association between discrimination and sleep disturbance., Results: Nearly half of participants reported PDU, of which 83.2% reported cannabis use. Higher levels of discrimination were associated with worse self-reported sleep disturbance scores. Additionally, participants with greater discrimination were more likely to have PDU. Surprisingly, participants with PDU had lower sleep disturbance scores., Conclusions: Our cross-sectional findings suggest that PDU partially suppressed the association between discrimination and sleep disturbance in TGNB people. Efforts to address PDU in TGNB adults may consider assessing sleep disturbance as a motivating factor for drug use and the potential role of discrimination in perpetuating PDU., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objective: Sexual minority women (SMW; e.g., lesbian, bisexual) report substantially higher rates of hazardous drinking (HD) than heterosexual women.Yet, few studies have examined sub-group differences. In this study, we investigated the relationship between gender self-concept and HD among SMW. Research consistently shows a link between heavier drinking and masculinity. SMW are more likely than heterosexual women to be gender nonconforming, and masculinity among SMW is associated with increased minority stress, a key HD risk factor., Methods: We used Wave 3 data from the Chicago Health and Life Experiences of Women study, a longitudinal study of SMW (N = 598), which assessed participants' self-perceived levels of masculinity and femininity and their perception of how masculine/feminine others viewed them. Using multivariable logistic regression, we examined the association between gender self-concept and past 12-month heavy episodic drinking (HED), drinking-related problems, and alcohol dependence., Results: Controlling for demographics and minority stress, greater masculinity (both self-perceived and perceptions by others) was associated with higher odds of HED and alcohol dependence. Masculinity as perceived by others was associated with higher odds of drinking-related problems. Neither femininity measure was associated with HD. Additionally, minority stress (i.e., discrimination, stigma, internalized stigma) did not account for the relationship between gender self-concept and HD., Conclusions/importance: In this sample, masculinity, particularly SMW's beliefs that others viewed them as masculine, was associated with HD. This association was not attributable to differences in minority stress and may be related to differences in gendered drinking norms, which could be targeted in intervention studies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Sexual minority women (SMW) report higher rates of heavy episodic drinking (HED) and adverse alcohol-related outcomes, including poor mental health, than heterosexual women. These disparities indicate a greater need for behavioral and mental health treatment for SMW. This study examined associations among alcohol outcomes, behavioral and mental health help-seeking, and treatment satisfaction among SMW by age, sexual identity, race/ethnicity, and income., Methods: Participants included a community sample of 695 SMW (M age  = 40.0, SD = 14.1; 74.1% lesbian, 25.9% bisexual; 37.6% White, 35.8% Black, 23.2% Latinx; 26.3% annual income $14,999 or less). We used bivariate analyses to characterize the sample's demographic characteristics and multivariable logistic regression analyses to examine associations among variables., Results: SMW subgroups based on age, race/ethnicity, and annual income differed in alcohol outcomes (i.e., HED, DSM-IV alcohol dependence, alcohol-related problem consequences, alcohol problem recognition, and motivation to reduce drinking); help-seeking; and treatment satisfaction. SMW who engaged in help-seeking for alcohol-related concerns were more likely than those who did not to meet criteria for DSM-IV alcohol dependence (adjusted odds ratio [aOR] = 7.13; 95% CI = 2.77; 18.36), endorse alcohol-related problem consequences (aOR = 11.44; 95% CI = 3.88; 33.71), recognize problematic drinking (aOR = 14.56; 95% CI = 3.37; 62.97), and report motivation to reduce drinking (aOR = 5.26; 95% CI = 1.74; 15.88). SMW's alcohol outcomes did not differ based on their satisfaction with treatment or with providers., Conclusions: This study's findings confirm SMW's elevated risk for HED and other alcohol-related outcomes and underscore the importance of identity-affirmative and accessible behavioral and mental health treatment for young, Black, and low-income SMW. Clinicians and intervention scientists should develop or enhance existing brief behavioral and mental health treatments for SMW engaging in HED who may not recognize that their drinking is problematic or who are not motivated to reduce drinking., (© 2022 by the Research Society on Alcoholism.)

Background: Alcohol, tobacco, and other drug use are among the most prevalent and important health disparities affecting sexual and gender minority (SGM; e.g., lesbian, gay, bisexual, transgender) populations. Although numerous government agencies and health experts have called for substance use intervention studies to address these disparities, such studies continue to be relatively rare., Method: We conducted a scoping review of prevention and drug treatment intervention studies for alcohol, tobacco, and other drug use that were conducted with SGM adults. We searched three databases to identify pertinent English-language, peer-reviewed articles published between 1985 and 2019., Results: Our search yielded 71 articles. The majority focused on sexual minority men and studied individual or group psychotherapies for alcohol, tobacco, or methamphetamine use., Conclusion: Our findings highlight the need for intervention research focused on sexual minority women and gender minority individuals and on cannabis and opioid use. There is also a need for more research that evaluates dyadic, population-level, and medication interventions., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

While the COVID-19 pandemic in the United States disproportionately impacts marginalized communities, no empiric US-based research has focused specifically on transgender and gender nonbinary (TGNB) people. We examined the pandemic's impact on an established longitudinal cohort of TGNB individuals ( N = 208) by administering an online survey between March-June 2020. We used multivariable linear regression to examine reduced LGBTQ/TGNB community support and disruptions in gender-affirming health care as predictors of psychological distress during the pandemic. We found that the pandemic exacerbated ongoing mental health disparities for TGNB individuals. Furthermore, reduced LGBTQ/TGNB support was associated with increased psychological distress during the pandemic. Interruption and/or delay in gender-affirming health care was not associated with increased psychological distress during the pandemic. Special attention is needed to address the unique ways in which TGNB individuals were affected by the COVID-19 pandemic. This includes increasing access to LGBTQ/TGNB community support and addressing long-standing health disparities.

Background: Prescription drug (PD) misuse, particularly opioid misuse, is a major US public health concern. While transgender and gender nonbinary (TGNB) individuals experience numerous health disparities, including substance use disparities, little research has focused on PD misuse in this population., Methods: Data for this secondary analysis come from the US Transgender Survey (N = 26,689). First, we examined bivariate differences in past 12-month PD misuse among binary transgender women, binary transgender men, nonbinary individuals assigned-female-at-birth (AFAB), and nonbinary individuals assigned-male-at-birth (AMAB). We then used multivariable logistic regression (separately based on sex-assigned-at-birth) to examine the relationship between gender-identity related discrimination and PD misuse., Results: PD misuse was significantly more common among binary transgender men (17.3 %), nonbinary AFAB individuals (18.7 %), and nonbinary AMAB individuals (18.0 %); compared to binary transgender women (13.5 %). In multivariable analyses, nonbinary identity was associated with higher odds of PD misuse among TGNB AFAB individuals (OR = 1.121; 95 %CI 1.021-1.232) and AMAB individuals (OR = 1.315; 95 % CI 1.133-1.527). Controlling for overall health status and psychological distress, public accommodations discrimination was associated with PD misuse among TGNB AMAB individuals (OR = 1.578, 95 %CI 1.354-1.839). Among both groups, healthcare discrimination was associated with PD misuse (AFAB OR = 1.388, 95 %CI 1.255-1.534; AMAB OR = 1.227, 95 %CI 1.073-1.404)., Conclusion: In this national sample of TGNB individuals, nonbinary individuals were at greater risk for PD misuse than binary individuals, possibly due to less societal affirmation. Similar to other TGNB health disparities, discrimination based on gender identity/expression was associated with PD misuse. This highlights the importance of interventions to reduce discrimination against TGNB individuals., (Copyright © 2020 Elsevier B.V. All rights reserved.)

(Copyright © William Byne et al. 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)., (Copyright © William Byne et al. 2020; Published by Mary Ann Liebert, Inc.)

Objective: While transgender people report higher rates of risky drinking than the general population, no studies have examined transgender alcohol use longitudinally. This study investigated minority stress and identity development predictors of improvement in risky drinking among transgender individuals., Methods: Data come from a multi-site, longitudinal cohort study of U.S. transgender individuals (N = 330) and include measures of enacted stigma, felt stigma, identity development, and risky alcohol use. Theory-driven, hierarchical multivariable logistic regression was used to investigate the hypothesis that minority stress and identity development factors are related to improvement in risky drinking between baseline and 1-year follow-up., Results: Baseline risky drinkers (n = 106; 37.1%) were younger and more likely to have female sex assigned at birth. At 1-year follow-up, 68 baseline risky drinkers (64.2%) reported persistent risky drinking, while 38 (35.8%) reported improved drinking. Controlling for demographics and study site, female sex assigned at birth and enacted stigma were associated with lower odds of improved drinking. Non-white/Hispanic race/ethnicity, felt stigma, change in gender role/expression for 1-5 years, and diffuse-avoidant identity style were associated with higher odds of improvement., Conclusions/importance: This is the first study to identity predictors of improvement in risky drinking among transgender individuals. Compared to trans-feminine individuals (assigned male at birth), trans-masculine individuals (assigned female at birth) were more likely to report risky drinking at baseline and had lower odds of improvement at 1-year follow-up. Improved drinking may be facilitated by preventing anti-transgender discrimination. Felt stigma and diffuse-avoidant identity style may lower alcohol risk via avoidance of drinking venues. Further research is needed to explicate these relationships and to inform culturally-tailored alcohol interventions for this at-risk population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Non-natively folded variants of superoxide dismutase 1 (SOD1) are thought to contribute to the pathogenesis of familial amyotrophic lateral sclerosis (ALS), however the relative toxicities of these variants are controversial. Here, we aimed to decipher the relationships between the different SOD1 variants (aggregated, soluble misfolded, soluble total) and the clinical presentation of ALS in the SOD1 G93A mouse. Using a multi-approach strategy, we found that the CNS regions least affected by disease had the most aggregated SOD1. We also found that the levels of aggregated SOD1 in the spinal cord were inversely correlated with the disease progression. Conversely, in the most affected regions, we observed that there was a high soluble misfolded/soluble total SOD1 ratio. Taken together, these findings suggest that soluble misfolded SOD1 may be the disease driver in ALS, whereas aggregated SOD1 may serve to sequester the toxic species acting in a neuroprotective fashion.

Purpose: Transgender individuals smoke tobacco at disproportionately higher rates than the general U.S. population, and concurrent use of gender-affirming hormones (estrogen or testosterone) and tobacco confers greater cardiovascular (CV) risk. This study examines the relationship between tobacco use and legal document gender-marker change, and medical/surgical interventions for gender transition., Methods: Data came from an Internet-based survey of U.S. trans-feminine (n = 631) and trans-masculine (n = 473) individuals. We used multivariable logistic regression to investigate the relationship between past 3-month tobacco use and legal document gender-marker change, hormone use, and gender-affirming surgery controlling for demographic covariates and enacted and felt stigma., Results: Compared to trans-feminine participants, trans-masculine individuals reported significantly higher rates of lifetime (74.4% vs. 63.5%) and past 3-month tobacco use (47.8% vs. 36.1%), and began smoking at an earlier age (14.5 vs. 15.5 years). Trans-feminine smokers reported significantly more frequent and heavier use. Adjusting for demographic covariates and enacted and felt stigma, legal document gender-marker change was associated with lower tobacco-use odds among trans-feminine individuals, whereas gender-affirming surgery predicted lower smoking odds among trans-masculine individuals. There were no significant differences in tobacco use by hormone use status., Conclusion: In this study, trans-masculine individuals were more likely to smoke and trans-feminine individuals reported heavier use. It is concerning that individuals receiving hormones did not report lower smoking rates, given the elevated CV risk of this combination. This is a missed opportunity to intervene on a major public health issue and highlights the need for smoking cessation interventions in this population.

Purpose of Review: Alcohol and drug use are common among youth. Rates are especially high among sexual and gender minority youth (SGMY; lesbian, gay, bisexual, transgender). We conducted a scoping review of research on risk and protective factors for substance use among SGMY published between 2013-2017., Recent Findings: Ninety-seven studies met our inclusion criteria. Most focused on individual-level minority stress risk factors, particularly stigma. Fewer studies addressed protective factors such as social support or affirming policies, and few focused on gender minority youth (GMY). We identified important, yet understudied differences by race/ethnicity, sex assigned at birth, and sexual orientation., Summary: Findings highlight growing interest in this topic as well as methodological/topical gaps in the literature. Research is needed to examine SGMY substance use in nationally representative samples; expand information about GMY; investigate racial/ethnic and sex/gender differences; improve measurement; and increase translation of findings to support prevention and treatment interventions for this at-risk population., Competing Interests: Conflicts of Interest The authors have no financial conflicts of interest to declare.

Regardless of their area of specialization, adult psychiatrists are likely to encounter gender-variant patients; however, medical school curricula and psychiatric residency training programs devote little attention to their care. This article aims to assist adult psychiatrists who are not gender specialists in the delivery of respectful, clinically competent, and culturally attuned care to gender-variant patients, including those who identify as transgender or transsexual or meet criteria for the diagnosis of Gender Dysphoria (GD) as defined by The Diagnostic and Statistical Manual of Mental Disorders (5th edition). The article will also be helpful for other mental health professionals. The following areas are addressed: evolution of diagnostic nosology, epidemiology, gender development, and mental health assessment, differential diagnosis, treatment, and referral for gender-affirming somatic treatments of adults with GD., Competing Interests: No author has any conflict of interest to report.

Background: Sexual risk behavior is now the primary vector of HIV transmission among substance users in the United States with gender as a crucial moderator of risk behavior., Objectives: The purpose of this study was to examine gender differences in factors (age, race/ethnicity, education) that predict main-partner unprotected sexual occasions (USO) using the unique platform of two parallel NIDA National Drug Abuse Treatment Clinical Trials Network gender-specific safer sex intervention trials., Methods: Baseline assessments of male (N = 430) and female (N = 377) participants included demographic characteristics; past 3-month sexual activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid use disorders. Using mixed effects generalized linear modeling of the main outcome USO, two-way interactions of gender with age, race/ethnicity, and education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid use disorder., Results: When adjusted for alcohol use disorder, the interaction of education and gender was significant. For men, a high school or greater education was significantly associated with more USO compared to men with less than high school. For women, greater than high school education was significantly associated with less USO compared to women with a high school education. None of the other interactions were significant when adjusted for cocaine/stimulant or opioid use disorder. Conclusions/Importance: This study demonstrates gender differences in the relationship of education, alcohol use disorder, and main-partner USO in individuals in substance abuse treatment. This underscores the importance of considering demographic and substance use factors in HIV sexual risk behavior and in crafting prevention messages for this population.

A copper chelator known as diacetylbis(N(4)-methylthiosemicarbazonato) copper II (CuATSM), has been reported to be efficacious in multiple transgenic SOD1 models of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder affecting motor neurons. Here we report that we also observed CuATSM efficacy on disease onset and progression in a standardized litter-matched and gender-balanced efficacy study using B6SJL-SOD1G93A/1Gur mice. We also report improved survival trends with CuATSM treatment. In addition, we report a lack of efficacy by unmetallated ATSM in the same model using the same standardized study design. These results add to existing evidence supporting an efficacious role for copper delivery using chaperone molecules in mouse models of ALS.

Objective: Transgender people face unique challenges when accessing health care, including stigma and discrimination. Most residency programs devote little time to this marginalized population., Methods: The authors developed a 90-min workshop to enhance residents' ability to empathize with and professionally treat transgender patients. Attendees completed pre-, post, and 90-day follow-up surveys to assess perceived empathy, knowledge, comfort, interview skill, and motivation for future learning., Results: Twenty-two residents (64.7 %) completed pre- and post-workshop surveys; 90.9 % of these completed the 90-day follow-up. Compared to baseline, there were statistically significant post-workshop increases in perceived empathy, knowledge, comfort, and motivation for future learning. However on 90-day follow-up, there were no statistically significant differences across any of the five domains, compared to baseline., Conclusions: This workshop produced significant short-term increases in resident professionalism toward transgender patients. However, extended follow-up results highlight the limitations of one-time interventions and call for recurrent programming to yield durable improvements.

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons. The mechanisms leading to motor neuron degeneration in ALS are unclear. However, there is evidence for involvement of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in ALS, notably in mutant SOD1 mediated models of ALS. Stress induced phosphorylation of the eIF2 alpha subunit by eukaryotic translation initiation factor 2-alpha kinase 3 Perk activates the UPR. Guanabenz is a centrally acting alpha2 adrenergic receptor agonist shown to interact with a regulatory subunit of the protein phosphatase, Pp1/Gadd34, and selectively disrupt the dephosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eif2alpha). Here we demonstrate that guanabenz is protective in fibroblasts expressing G93A mutant SOD1 when they are exposed to tunicamycin mediated ER stress. However, in contrast to other reports, guanabenz treatment accelerated ALS-like disease progression in a strain of mutant SOD1 transgenic ALS mice. This study highlights challenges of pharmacological interventions of cellular stress responses in whole animal models of ALS.

Background: Primary health care does not adequately respond to populations known to have high needs such as those with compounding jeopardy from chronic conditions, poverty, minority status and age; as such populations report powerlessness., Objective: To explore what poor older adults with chronic conditions who mostly belong to ethnic minority groups say they want from clinicians., Setting and Participants: Participants were older adults whose chronic conditions were severe enough to require hospital admission more than twice in the previous 12 months. All participants lived in poor localities in Auckland, New Zealand's largest city., Methods: Forty-two in-depth interviews were conducted and analysed using qualitative description., Results: An outward acceptance of health care belied an underlying dissatisfaction with low engagement. Participants did not feel heard and wanted information conveyed in a way that indicated clinicians understood them in the context of their lives. Powerlessness, anger, frustration and non-concordance were frequent responses., Discussion and Conclusions: Despite socio-cultural and disease-related complexity, patients pursue the (unrealised) ideal of an engaged therapeutic relationship with an understanding clinician. Powerlessness means that the onus is upon the health system and the clinician to engage. Engagement means building a relationship on the basis of social, cultural and clinical knowledge and demonstrating a shift in the way clinicians choose to think and interact in patient care. Respectful listening and questioning can deepen clinicians' awareness of patients' most important concerns. Enabling patients to direct the consultation is a way to integrate clinician expertise with what patients need and value., (© 2012 John Wiley & Sons Ltd.)

Treatment options for people living with amyotrophic lateral sclerosis (ALS) are limited and ineffective. Recently, dexpramipexole (RPPX) was advanced into human ALS clinical trials. In the current studies, we investigated RPPX in two parallel screening systems: 1) appropriately powered, sibling-matched, gender-balanced survival efficacy screening in high-copy B6-SJL-SOD1G93A/Gur1 mice, and 2) high-content neuronal survival screening in primary rat cortical neurons transfected with wild-type human TDP43 or mutant human TDP43. In both cases, we exposed the test systems to RPPX levels approximating those achieved in human Phase II clinical investigations. In SOD1G93A mice, no effect was observed on neuromotor disease progression or survival. In primary cortical neurons transfected with either mutant or wild-type human TDP43, a marginally significant improvement in a single indicator of neuronal survival was observed, and only at the 10 µM RPPX treatment. These systems reflect both mutant SOD1- and TDP43-mediated forms of neurodegeneration. The systems also reflect both complex non-cell autonomous and neuronal cell autonomous disease mechanisms. The results of these experiments, taken in context with results produced by other molecules tested in both screening systems, do not argue positively for further study of RPPX in ALS.

ALS therapy development has been hindered by the lack of rodent animal models. The discovery of TDP-43, a transcription factor that accumulates in the cytoplasm of motor neurons (MNs) in most cases of ALS, prompted attempts to develop TDP-43-based models of the disease. The current study sought to examine, in extensive detail, the emerging disease phenotype of a transgenic mouse model that overexpresses a mutant human TDP-43 (hTDP-43) gene under mouse prion promoter control. Careful attention was given to ALS-like characteristics to determine the appropriateness of this model for testing therapies for ALS. In light of previous reports that gastrointestinal (GI) dysfunction is responsible for early death in these mice, gut immunohistochemistry (IHC) and longitudinal gut motility assays were used to identify the onset and the progression of these defects. IHC studies revealed that site-specific overexpression of the hTDP-43 transgene in colonic myenteric plexes resulted in progressive neurodegeneration in this region. This change was associated with progressively reduced GI motility, culminating in frank stasis that was primarily responsible for decreasing longevity in these mice. The disease phenotype was gender- and genetic background-dependent, with congenic C57BL/6J male mice exhibiting the most aggressive form of the disease. Spinal cord IHC revealed ubiquitin-positive inclusions, but not TDP-43 aggregates, in the cytoplasm of MNs. Neither gender exhibited compelling ALS-like neuromuscular deficits, irrespective of age. While this model may be useful for studying GI tract neurodegeneration, in its present state it does not display a phenotype suitable for testing ALS therapeutics., (© 2013 Published by Elsevier B.V.)

Studies document a significant association between victimization from intimate partner violence (IPV) and sexually transmitted infections (STIs) and HIV among substance using women in Russia and elsewhere, but no study has examined IPV perpetration and STI among Russian men or HIV-infected men in Eastern Europe. This study was designed to assess the association between lifetime history of IPV perpetration and STI (lifetime and current) among substance using HIV-infected men in Russia. Cross-sectional analyses were conducted with baseline data from 415 male participants enrolled in a randomized HIV intervention clinical trial [the HERMITAGE Study]. Participants were HIV-infected men reporting recent heavy alcohol use and unprotected sex in St. Petersburg, Russia. Baseline surveys assessed demographics, IPV perpetration, risk behaviors, and STI history. Current STI was assessed via blood testing for syphilis and urine testing for gonorrhea, Chlamydia and Trichomonas. Multiple logistic regression analyses were used to assess the association between history of IPV with lifetime and current STI. Participants were aged 20-57 years. Almost half of participants (46%) reported a history of IPV perpetration; 81% reported past 30-day binge alcohol use, and 43% reported past 30-day injection drug use. Past and current STI was 41% and 12%, respectively. Men reporting a history of IPV perpetration had significantly higher odds of reporting ever having an STI (AOR=1.6, 95% CI=1.1, 2.4) but lower odds of testing positive for a current STI (AOR=0.50, 95% CI=0.26, 0.96). These findings demonstrate that a history of male IPV perpetration is common in HIV-infected Russian men and associated with a history of STI. Programmatic work toward IPV prevention is needed in Russia and may be beneficial in mitigating STIs, but more research is needed to understand how and why the association between IPV and STI changes over time in this population.

Although sexual minority (SM) youth are at an increased risk for being bullied and experiencing depression, it is unclear how caregiver support is interrelated with those variables. Therefore, we sought to assess: (a) the prevalence of nonphysical bullying, depressive symptomatology, and caregiver support among heterosexual and SM girls, (b) the association between caregiver support and bullying in both groups, and (c) whether sexual orientation moderates the interactive effect of caregiver support and bullying on depressive symptoms. Data come from a survey of students in 22 Boston public high schools; 99 of the 832 girls in the analytic sample were SM. We used chi-square statistics to examine group differences, and multiple regression to estimate the association between the caregiver support, sexual orientation, being bullied, and depressive symptomatology. SM girls reported similar levels of caregiver support as heterosexual girls, but reported higher levels of depressive symptomatology. They were also more likely to report nonphysical bullying. Tests for interactions were not statistically significant, suggesting that bullying, caregiver support, and sexual orientation are independently associated with depressive symptomatology.

Many nurses are burned out, exhausted and have a high intent to leave their jobs. These factors, when experienced over a period of time, are consistent with the development of mental illness. This study takes a collective autoethnographical approach to mental illness in the nursing workplace by focusing on the stories of nurses who have experienced mental illness in clinical practice. It highlights three ways in which nursing and mental illness are connected; the nurse who is vulnerable to mental illness prior to entering the profession, the nurse who develops mental illness that is independent of her work but is nevertheless impacted by it, and the nurse who develops mental illness as a result of her work and/or role. This paper explores the hyphenated lives and bullying these nurses experience, and recommends strategies that the profession, employing organisations, and individuals can adopt to reduce nurses' progression from stress to distress and mental illness.