RAD140 (Testolone) negatively impacts skeletal muscle adaptation, frailty status and mortality risk in female mice.

RAD140 is a selective androgen receptor modulator that produces anabolic effects within skeletal muscle. Thus, RAD140 may be effective at treating sarcopenia. No long-term studies have investigated how RAD140 influences strength in ageing muscle. This study aimed to determine how 10 weeks of RAD140 supplementation impacts strength, recovery from exercise, and overall health in ageing mice. Young and adult females were assigned to receive RAD140 (5 mg/kg) or a control solution. Dorsiflexor muscles were exposed to repeated bouts of eccentric contractions, and torque was measured before and after each bout. Adaptive potential and strength gains were calculated to assess the efficacy of RAD140 in muscle, while frailty status and mortality risk were used to measure health span. Supplementation of RAD140 increased frailty status and mortality risk in the young and adult treated groups compared to the controls (p ≤ 0.042). RAD140 decreased adaptive potential in young (p = 0.040) but not adult mice (p = 0.688). Torque did not differ between groups after 2-3 weeks of recovery (p ≥ 0.135). In conclusion, long-term RAD140 supplementation reduced indices of overall health and failed to improve strength in female mice, suggesting that RAD140 (at a 5mg/kg dosage) may be more detrimental than beneficial in delaying or preventing sarcopenia.

Neuromuscular mechanisms of weakness in a mouse model of chronic alcoholic myopathy.

BACKGROUND: Weakness is a common clinical symptom reported in individuals with chronic alcohol use disorder. However, it remains unclear whether low strength in these individuals is directly related to excessive ethanol intake, other deleterious factors (lifestyle, environment, genetics, etc.), or a combination of both. Therefore, we examined whether (and how) ethanol reduces the muscle's force-producing capacity using a controlled in vivo preclinical mouse model of excessive ethanol intake. METHODS: To establish whether chronic ethanol consumption causes weakness, C57BL/6 female mice consumed 20% ethanol for 40 weeks (following a 2-week ethanol ramping period), and various measures of muscular force were quantified. Functional measures included all-limb grip strength and in vivo contractility of the left ankle dorsiflexors and plantarflexors. Once confirmed that mice consuming ethanol were weaker than age-matched controls, we sought to determine the potential neuromuscular mechanisms of muscle dysfunction by assessing neuromuscular excitation, muscle quantity, and muscle quality. RESULTS: Mice consuming chronic ethanol were 13 to 16% weaker (p ≤ 0.016) than controls (i.e., mice consuming 100% water) with the negative impact of ethanol on voluntary grip strength (ƞ2  = 0.603) being slightly larger than that of electrically stimulated muscle contractility (ƞ2  = 0.482). Relative to controls, lean mass and muscle wet masses were 9 to 16% lower in ethanol-consuming mice (p ≤ 0.048, ƞ2  ≥ 0.268). No significant changes were observed between groups for indices of neuromuscular excitation at the level of the motor unit, neuromuscular junction, or plasmalemma (p ≥ 0.259, ƞ2  ≤ 0.097), nor was muscle quality altered after 40 weeks of 20% ethanol consumption (p ≥ 0.695, ƞ2  ≤ 0.012). CONCLUSIONS: Together, these findings establish that chronic ethanol consumption in mice induces a substantial weakness in vivo that we interpret to be primarily due to muscle atrophy (i.e., reduced muscle quantity) and possibly, to a lesser degree, loss of central neural drive.

The Language of Substance Use and Recovery: Novel Use of the Go/No-Go Association Task to Measure Implicit Bias.

Previous research has found initial evidence that word choice impacts the perception and treatment of those with behavioral health disorders through explicit bias (i.e., stigma). A more robust picture of behavioral health disorder stigma should incorporate both explicit and implicit bias, rather than relying on only one form. The current study uses the Go/No-Go Association Task to calculate a d' (sensitivity) indexed score of automatic attitudes (i.e., implicit associations) to two terms, "addict" and "person with substance use disorder." Participants have significantly more negative automatic attitudes (i.e., implicit bias) toward the term "addict" in isolation as well as when compared to "person with a substance use disorder." Consistent with previous research on explicit bias, implicit bias does exist for terms commonly used in the behavioral health field. "Addict" should not be used in professional or lay settings. Additionally, these results constitute the second pilot study employed the Go/No-Go Association Task in this manner, suggesting it is a viable option for continued linguistic stigma related research.

Biased labels: An experimental study of language and stigma among individuals in recovery and health professionals.

BACKGROUND: Labels such as "addict" and "substance abuser" have been found to elicit implicit and explicit stigma among the general public previously. The difference in the levels of this bias among individuals in recovery and those employed in the health profession has not yet been identified, however. The current study seeks to answer this question using measures of implicit bias. METHODS: A subset sample (n = 299) from a previously completed study (n = 1288) was selected for analysis. Mixed-model ANOVA tests were completed to identify variance between d-prime automatic association scores with the terms "addict" and "substance abuser" among individuals in recovery and those identified as working in the health professions. RESULTS: Individuals in recovery did not have lower negative associations with either term, whereas individuals employed as health professionals had greater negative associations with the term "substance abuser" but did not have greater negative associations with the term "addict." CONCLUSIONS: Results provide further evidence that previously identified stigmatizing labels have the potential to influence medical care and medical practitioner perceptions of individuals with substance use disorders and should be avoided. Further exploration into the role negative associations derived from commonly used labels have in the individual recovery process is needed to draw appropriate recommendations.

Peer-delivered harm reduction and recovery support services: initial evaluation from a hybrid recovery community drop-in center and syringe exchange program.

BACKGROUND: Recovery from substance use disorder (SUD) is often considered at odds with harm reduction strategies. More recently, harm reduction has been categorized as both a pathway to recovery and a series of services to reduce the harmful consequences of substance use. Peer recovery support services (PRSS) are effective in improving SUD outcomes, as well as improving the engagement and effectiveness of harm reduction programs. METHODS: This study provides an initial evaluation of a hybrid recovery community organization providing PRSS as well as peer-based harm reduction services via a syringe exchange program. Administrative data collected during normal operations of the Missouri Network for Opiate Reform and Recovery were analyzed using Pearson chi-square tests and Monte Carlo chi-square tests. RESULTS: Intravenous substance-using participants (N = 417) had an average of 2.14 engagements (SD = 2.59) with the program. Over the evaluation period, a range of 5345-8995 sterile syringes were provided, with a range of 600-1530 used syringes collected. Participant housing status, criminal justice status, and previous health diagnosis were all significantly related to whether they had multiple engagements. CONCLUSIONS: Results suggest that recovery community organizations are well situated and staffed to also provide harm reduction services, such as syringe exchange programs. Given the relationship between engagement and participant housing, criminal justice status, and previous health diagnosis, recommendations for service delivery include additional education and outreach for homeless, justice-involved, LatinX, and LGBTQ+ identifying individuals.

Longitudinal assessment of strength and body composition in a mouse model of chronic alcohol-related myopathy.

BACKGROUND: Excessive, chronic alcohol consumption can result in muscle atrophy and weakness (i.e., alcoholic myopathy) that impairs the quality of life. However, the precise mechanisms responsible for ethanol's detrimental impact on skeletal muscle have not been fully elucidated, in part due because the time course of disease development and progression are not well established. Therefore, we examined muscle strength and body composition longitudinally using an established preclinical mouse model of chronic alcoholic myopathy. METHODS: To establish a time course of chronic alcoholic myopathy, we fed High Drinking in the Dark (HDID) female mice (n = 7) 20% ethanol for ~32 weeks (following a 2-week ethanol ramping period). We assessed in vivo isometric contractility of the left ankle dorsiflexor and lean mass via NMR every 4 weeks. Outcomes were compared with age-matched control HDID mice that did not consume ethanol (n = 8). RESULTS: At study completion, mice who consumed ethanol were 12% weaker than control mice (p = 0.015). Compared to baseline, consuming ethanol resulted in an acute transient reduction in dorsiflexion torque at Week 4 (p = 0.032) that was followed by a second, more sustained reduction at Week 20 (p < 0.001). Changes in lean mass paralleled those of dorsiflexor torque, with ~40% of the variance in dorsiflexor torque being explained by the variance in lean mass of the ethanol group (p < 0.001). Dorsiflexor torque normalized to lean mass (mN·m/g lean mass) did not differ between the ethanol and control groups from Weeks 4 to 32 (p ≥ 0.498). CONCLUSIONS: These results indicate that reductions in muscle mass and strength due to chronic, excessive ethanol intake are dynamic, not necessarily linear, processes. Moreover, the findings confirm that ethanol-induced weakness is primarily driven by muscle atrophy (i.e., loss of muscle quantity). Future studies should consider how chronic alcoholic myopathy develops and progresses rather than identifying changes after it has been diagnosed.

Excessive Ethanol Intake in Mice Does Not Impair Recovery of Torque after Repeated Bouts of Eccentric Contractions.

PURPOSE: Alcoholics develop muscle atrophy and weakness from excessive ethanol (EtOH) intake. To date, most research has examined outcomes of alcohol-induced atrophy and weakness under basal or unstressed conditions despite physical stress being a normal occurrence in a physiological setting. Therefore, this study set out to determine if recovery of torque is impaired after repetitive bouts of physical stress in skeletal muscle during excessive short-term (experiment 1) and long-term (experiment 2) EtOH consumption. METHODS: Twenty male and female mice were assigned to receive either 20% EtOH in their drinking water or 100% water. Short- and long-term consumption was predetermined to be EtOH intake starting at 4 and 26 wk, respectively. Anterior crural muscles performed repeated bouts of physical stress using in vivo eccentric contractions, with tetanic isometric torque being measured immediately pre- and postinjury. A total of 10 bouts were completed with 14 d between each bout within bouts 1-5 (experiment 1) and bouts 6-10 (experiment 2), and 12 wk between bouts 5 and 6. RESULTS: Mice consuming EtOH had blood alcohol concentrations up to 270 mg·dL -1 . In experiment 1, five bouts of eccentric contractions did not reduce recovery of torque, regardless of sex or EtOH treatment ( P ≥ 0.173). Similarly, in experiment 2, preinjury torques did not differ from day 14 values regardless of sex or treatment ( P ≥ 0.322). However, there was a group effect in female mice for bouts 6 and 10 during experiment 2, with female EtOH mice being weaker than controls ( P ≤ 0.002). CONCLUSIONS: Excessive short- or long-term EtOH misuse in a mouse model did not affect the muscle's ability to regain strength after repeated bouts of eccentric contractions, suggesting that EtOH may not be as detrimental to recovery as once predicted.

How do gravity alterations affect animal and human systems at a cellular/tissue level?

The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: "How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?" This is one of the five major scientific issues of the ESA roadmap "Biology in Space and Analogue Environments". Despite the many studies conducted so far on spaceflight adaptation mechanisms and related pathophysiological alterations observed in astronauts, we are not yet able to elaborate a synthetic integrated model of the many changes occurring at different system and functional levels. Consequently, it is difficult to develop credible models for predicting long-term consequences of human adaptation to the space environment, as well as to implement medical support plans for long-term missions and a strategy for preventing the possible health risks due to prolonged exposure to spaceflight beyond the low Earth orbit (LEO). The research activities suggested by the scientific community have the aim to overcome these problems by striving to connect biological and physiological aspects in a more holistic view of space adaptation effects.

Dynamic labeling discernment: Contextual importance of self-identifiers for individuals in recovery.

Recent studies associate identifiers, such as "alcoholic/addict", with stigma, discrimination, and service deficits. Yet, little is known about why and how self-identifiers are chosen. This study analyzed qualitative responses from individuals (N = 42) in recovery from substance use disorders (SUDs) concerning their use of "alcoholic/addict" or "person with a SUD". Evaluative structure and generative theories were developed via latent content analysis and grounded theory. Secondary analysis evidenced four thematic constructs: contextual significance, flexibility/rigidity, leveraging identity to counteract stigma, and indications of identity integration/disintegration. Some individuals indicated the contextual utility of certain identifiers, regardless of associated stigma and bias.

"Abusing Addiction": Our Language Still Isn't Good Enough.

BACKGROUND: Previous research has found initial evidence that word choice impacts the perception and treatment of those with behavioral health disorders. These previous studies have relied on vignette-based methodologies, however, and a more quantifiable index of the stigma words can produce is needed. METHOD: The current study uses the Go/No-Go Association Task to calculate a d-prime (sensitivity) indexed score of automatic attitudes to two terms, "substance abuser" and "person with substance use disorder". RESULTS: Participants have significantly more negative automatic attitudes towards the term "substance abuser", as compared to "person with a substance use disorder". CONCLUSION: Consistent with previous research, implicit bias does exist for terms commonly used in the behavioral health field. "Substance Abuser" and its derivatives should not be used in professional or lay settings.

Recovery dialects: A pilot study of stigmatizing and nonstigmatizing label use by individuals in recovery from substance use disorders.

Previous research has found language used to describe individuals with a substance use disorder (SUD; e.g., "addict," "substance abuser") contributes to and elicits negative bias among the general public and health care professionals. However, the prevalence in which recovering individuals use these labels to self-identify and the impact of such labels are unknown. The current pilot study, a cross-sectional design, examined the usage of two labels ("addict," "person with a SUD") as well as the differences in recovery outcomes among individuals in recovery. Participants (n = 54) used both labels at high rates ("addict": 66.67%; "person with a SUD": 38.89%), though mutually exclusive use was lower ("addict" only: 35.19%, "person with a SUD" only: 7.5%). Common label use settings included mutual-aid recovery meetings, with friends and family, and on social media. Analysis of variance tests found no statistically significant differences between label groups for recovery capital, self-esteem, internalized stigma and shame, flourishing, or length in recovery. Descriptively, participants using only "person with a SUD" had more positive outcomes, although these individuals also had higher levels of internalized shame. Results suggest that language may have only a marginal impact on individuals in recovery, although professionals and the general public should continue to avoid using stigmatizing labels. Additionally, many individuals in recovery have the ability to discern context and setting, switching between positive and negative labels as appropriate. Future research is warranted given these pilot findings and should focus on long-term impacts of self-labeling and internalized stereotypes among individuals in recovery. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Reducing harm and promoting recovery through community-based mutual aid: Characterizing those who engage in a hybrid peer recovery community organization.

BACKGROUND: Peer-based support services are often used within harm reduction organizations, and more recently within recovery community organizations (RCO). Identifying the characteristics of individuals who engage with these novel RCOs is needed. Additionally, conducting collaborative research with communities of people who use drugs (PWUD) or are in recovery is an effective and rewarding approach that allows individuals to take ownership and play a critical role in the study. METHODS: This exploratory study employs a community-based participatory research (CBPR) framework in partnership with a peer-led hybrid recovery community organization, Rebel Recovery, in Florida. Peer staff participated in all phases of the study, helping to inform the study protocol, data collection, analysis, interpretation, and results write-up. A cross-sectional survey instrument was used to collect consumer intake data. Pearson Chi-square tests and multivariate binomial logistic regressions were used to examine relationships between consumer characteristics and service utilization. RESULTS: Consumers (n = 396) of Rebel Recovery peer support services had a mean age of 35.60 years (SD = 9.74). Many were experiencing homelessness (35.4%), unemployed (69.7%), high school graduates or GED holders (68.2%) and had a last year income of less than $10,000 (58.3%). The majority were users of heroin primarily (70.7%), with intravenous use being the preferred route of administration (63.9%). Exploratory analysis found that gender, marital status, and involvement in the child welfare system were significantly related to primary substance of use. Past 30-day engagement in recovery meetings had several statistically significant predictors including primary substance of use, age, housing status, annual income level, past-30-day arrests, tobacco use, and alcohol harm perception. Process findings from the CBPR methods used reconfirm the value of including peers in research involving PWUD and individuals in recovery. CONCLUSIONS: Results suggest that peer-based support services at a hybrid recovery community organization can successfully engage populations that are often underserved (i.e., experiencing homelessness, involved in drug court, intravenous users, etc.). Significant relationships identified in the exploratory analysis suggest that additional education concerning overdose and the potential benefits of recovery meetings may be useful for specific consumers. Additionally, several recommendations and benefits of engaging in community-based participatory research with peer-led organizations are made for future research.

Responding to the opioid and overdose crisis with innovative services: The recovery community center office-based opioid treatment (RCC-OBOT) model.

Opioid use disorder (OUD) and opioid-related overdose mortality are major public health concerns in the United States. Recently, several community-based and professional innovations - including hybrid recovery community organizations, peer-based emergency department warm handoff programs, emergency department buprenorphine induction, and low-threshold OUD treatment programs - have emerged or expanded in an effort to address significant obstacles to providing patients the care needed for OUD and to reduce the risk of overdose. Additional innovations are needed to address the crisis. Building upon the foundational frameworks of each of these recent innovations, a new model of OUD pharmacotherapy is proposed and discussed: the Recovery Community Center Office-Based Opioid Treatment model. Additionally, two potential implementation scenarios, the overdose and non-overdose event protocols, are detailed for communities, peers, and practitioners interested in implementing the model. Potential barriers to implementation of the model include service reimbursement, licensing regulations, and organizational concerns. Future research should seek to validate the model and to identify actual implementation and sustainability barriers and best practices.

Systemic barriers in substance use disorder treatment: A prospective qualitative study of professionals in the field.

BACKGROUND: The US is in the midst of one of the largest public health crises in recent history with over 63,000 drug poisoning deaths in 2016 and a projected annual economic cost of over $420 billion. With the rise of deaths and economic burden related to substance use, it is paramount that systemic barriers within the treatment industry be identified and resolved. METHODS: Data were collected from US substance use treatment professionals (N = 182) in the fall of 2016. Thematic analysis with axial coding was used on anonymized responses to an online open-ended survey. Additional ad hoc testing for variance (education, generation, regional location, and employment) was completed using Monte Carlo chi-square analyses. RESULTS: 7 major themes emerged: 1) additional training, education, and use of evidence-based practices, 2) expansion of treatment services, 3) increased resources, 4) stigma reduction, 5) increased collaboration and leadership, 6) reductions in regulations, requirements, and incentives, and 7) expansion of recovery support services. Participant response yielded a significant relationship between employment type (p = 0.002) and regional location (p = 0.046). CONCLUSIONS: Systemic barriers in the treatment field are prevalent from the perspective of professionals engaged in the field. While previously identified barriers are still present, newly reported barriers include: 1) lack of treatment services (e.g., capacity), 2) lack of technological resources (e.g., technological support tools), 3) lack of recovery support services (e.g., recovery housing), 4) lack of collaboration and leadership (e.g., communication and partnership), and 5) increasing unethical practices in the field (e.g., incentive-based patient brokering).

Substance use, recovery, and linguistics: The impact of word choice on explicit and implicit bias.

BACKGROUND: The general public, treatment professionals, and healthcare professionals have been found to exhibit an explicit negative bias towards substance use and individuals with a substance use disorder (SUD). Terms such as "substance abuser" and "opioid addict" have shown to elicit greater negative explicit bias. However, other common terms have yet to be empirically studied. METHODS: 1,288 participants were recruited from ResearchMatch. Participants were assigned into one of seven groups with different hypothesized stigmatizing and non-stigmatizing terms. Participants completed a Go/No Association Task (GNAT) and vignette-based social distance scale. Repeated-measures ANOVAs were used to analyze the GNAT results, and one-way ANOVAs were used to analyze vignette results. RESULTS: The terms "substance abuser", "addict", "alcoholic", and "opioid addict", were strongly associated with the negative and significantly different from the positive counterterms. "Relapse" and "Recurrence of Use" were strongly associated with the negative; however, the strength of the "recurrence of use" positive association was higher and significantly different from the "relapse" positive association. "Pharmacotherapy" was strongly associated with the positive and significantly different than "medication-assisted treatment". Both "medication-assisted recovery" and "long-term recovery" were strongly associated with the positive, and significantly different from the negative association. CONCLUSIONS: Results support calls to cease use of the terms "addict", "alcoholic", "opioid addict", and "substance abuser". Additionally, it is suggested that "recurrence of use" and "pharmacotherapy" be used for their overall positive benefits. Both "medication-assisted recovery" and "long-term recovery" are positive terms and can be used when applicable without promoting stigma.