Endocannabinoid Signaling is Critical for Habit Formation

Extended training can induce a shift in behavioral control from goal-directed actions, which are governed by action-outcome contingencies and sensitive to changes in the expected value of the outcome, to habits which are less dependent on action-outcome relations and insensitive to changes in outcome value. Previous studies in rats have shown that interval schedules of reinforcement favor habit formation while ratio schedules favor goal-directed behavior. However, the molecular mechanisms underlying habit formation are not well understood. Endocannabinoids, which can function as retrograde messengers acting through presynaptic CB1 receptors, are highly expressed in the dorsolateral striatum, a key region involved in habit formation. Using a reversible devaluation paradigm, we confirmed that in mice random interval schedules also favor habit formation compared with random ratio schedules. We also found that training with interval schedules resulted in a preference for exploration of a novel lever, whereas training with ratio schedules resulted in less generalization and more exploitation of the reinforced lever. Furthermore, mice carrying either a heterozygous or a homozygous null mutation of the cannabinoid receptor type I (CB1) showed reduced habit formation and enhanced exploitation. The impaired habit formation in CB1 mutant mice cannot be attributed to chronic developmental or behavioral abnormalities because pharmacological blockade of CB1 receptors specifically during training also impairs habit formation. Taken together our data suggest that endocannabinoid signaling is critical for habit formation

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

A study protocol to explore and implement community-based point-of-care COVID-19 testing for women who use drugs in Baltimore, Maryland: The CARE study.

Women who use drugs (WWUD) experience structural vulnerabilities (e.g., housing, food insecurities) and comorbidities that elevate their susceptibility to more severe COVID-19 symptoms or fatality compared to similarly-aged women who do not use illicit drugs. Testing is a cornerstone of effective COVID prevention, however, entrenched barriers to healthcare utilization means that WWUD may have diminished accessing to COVID testing. The CARE (COVID Action Research Engagement) study first examines predisposing and enabling factors that predict COVID testing uptake over six months (baseline, 3-, and 6-month follow-up) among a cohort of WWUD (N = 250) in Baltimore, Maryland, providing a nuanced and holistic understanding of how to meaningfully engage WWUD in COVID testing. Then, point-of-care COVID testing will be implemented on a mobile outreach van affiliated with a local community-based organization primarily serving WWUD; anonymous surveys of mobile outreach guests (N = 100) will assess feasibility and acceptability of this integrated testing. The study is grounded in the Behavioral Model for Vulnerable Populations and the Theoretical Framework of Acceptability. We hypothesize that point-of-care COVID testing integrated into a low-barrier harm reduction service, such as a mobile outreach program, will be an enabling environment for COVID testing uptake in part by reducing structural impediments to testing and will be highly feasible and acceptable to participants. Strengths, limitations, and plans for results dissemination are discussed

“We are not gays… don’t tell me those things”: engaging ‘hidden’ men who have sex with men and transgender women in HIV prevention in Myanmar

Abstract Background In Myanmar, HIV is concentrated among key populations, yet less than half of the estimated 250,000 men who have sex with men (MSM) and transgender women (TW) report recent HIV testing. As many as 50% of MSM and TW may conceal their same-sex preferences and behaviors, yet little is known about the barriers faced by those who are locally regarded as ‘hidden’ – that is, MSM who do not disclose same-sex preferences and/or identify as gay. This study explored specific barriers to accessing HIV testing and other prevention services among ‘hidden’ MSM to inform appropriate models of service delivery. Methods In-depth interviews with MSM (n = 12) and TW (n = 13) and focus group discussions (FGD) with MSM and TW community members, leaders and key informants (n = 35) were undertaken in Yangon during June – September 2015. Participants were recruited by word-of-mouth by trained peer data collectors. Responses to questions from semi-structured guides were transcribed and coded using Atlas Ti. Codes were based on key domains in the guides and applied to transcripts to identify and analyze emerging themes. Results Fear of stigma and discrimination and the need to meet gender expectations were key reasons for non-disclosure of same-sex preferences and behaviors; this typically manifested as avoidance of other MSM and settings in which sexual identity might be implicated. These concerns influenced preference and interaction with HIV services, with many avoiding MSM-specific services or eschewing HIV testing services entirely. The difficulties of engaging hidden MSM in HIV prevention was strongly corroborated by service providers. Conclusion Hidden MSM face multiple barriers to HIV testing and prevention. Strategies cognizant of concerns for anonymity and privacy, such as One-Stop Shop services and online-based health promotion, can discretely provide services appropriate for hidden MSM. Enhanced capacity of peer-service providers and mainstream health staff to identify and respond to the psychosocial challenges reported by hidden MSM in this study may further encourage service engagement. Overarching strategies to strengthen the enabling environment, such as legal reform and LGBTI community mobilisation, can lessen stigma and discrimination and increase hidden MSM’s comfort and willingness to discuss same-sex behavior and access appropriate services

Determining the scope of attacks on health in four governorates of Syria in 2016: Results of a field surveillance program

Violent attacks on and interferences with hospitals, ambulances, health workers, and patients during conflict destroy vital health services during a time when they are most needed and undermine the long-term capacity of the health system. In Syria, such attacks have been frequent and intense and represent grave violations of the Geneva Conventions, but the number reported has varied considerably. A systematic mechanism to document these attacks could assist in designing more protection strategies and play a critical role in influencing policy, promoting justice, and addressing the health needs of the population

Determining the scope of attacks on health in four governorates of Syria in 2016: Results of a field surveillance program

Violent attacks on and interferences with hospitals, ambulances, health workers, and patients during conflict destroy vital health services during a time when they are most needed and undermine the long-term capacity of the health system. In Syria, such attacks have been frequent and intense and represent grave violations of the Geneva Conventions, but the number reported has varied considerably. A systematic mechanism to document these attacks could assist in designing more protection strategies and play a critical role in influencing policy, promoting justice, and addressing the health needs of the population