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BackgroundAccording to the new AASLD Practice Guidance, all patients with primary sclerosing cholangitis (PSC) should be considered for participation in clinical trials. However, PSC's rarity has posed challenges to characterizing patient interest in trial participation and identifying predictors of patient willingness to participate in drug trials.MethodsPSC Partners Seeking a Cure developed the "Our Voices" survey to inform the development of the Externally-Led Patient-Focused Drug Development Forum, an FDA initiative to capture patient experiences and perspectives on drug development.ResultsOf 797 survey respondents from over 30 countries, 536 (67%) identified slowing disease progression as the most important outcome. Eighty-nine percent identified their hepatologist/gastroenterologist as someone they would approach for advice about trials. Although 61% reported being willing to participate in drug trials, only 26% had ever been asked to participate. Notable barriers to trial involvement included unknown long-term risks (71%), long travel times to the study center (32%), and a liver biopsy requirement (27%). On multivariable logistic regression, pruritus (OR 1.62, 95% CI: 1.09-2.40, p = 0.017) was positively associated with willingness to participate in disease-modifying therapy trials, while jaundice (OR 0.34, 95% CI: 0.19-0.61, p < 0.001) and inflammatory bowel disease (OR 0.64, 95% CI: 0.42-0.98, p = 0.038) were negatively associated. Pruritus (OR 2.25, 95% CI: 1.50-3.39, p < 0.001) was also independently associated with willingness to participate in symptom treatment trials.ConclusionsMost patients with PSC report interest in participating in clinical trials, but few have been asked to participate. Referral of patients with PSC by their hepatologist/gastroenterologist to clinical trials and patient education on trial participation are vital to closing the gap between trial interest and participation. Pruritus may serve as a key indicator of patient interest in trial participation.

ObjectiveTo longitudinally evaluate differences in HIV viral suppression (

It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non-randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2-4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal.

BackgroundStarting in 2008, Vietnam's national MMT program expanded quickly, but it is struggling with increasing attrition rates and poor adherence among patients. Several studies have reported on MMT retention and adherence, but no overview has yet been published. The objective of this study is to fill that gap and to review factors associated with retention and adherence in MMT in Vietnam.MethodsA systematic search was conducted using databases of literature - Pubmed, Cochrane, Scopus, Academic search premiere, and SoINDEX. Peer-reviewed empirical studies with full text in English discussing retention attrition and adherence regarding MMT in Vietnam were selected. The results were synthesized using qualitative methods.ResultsAdherence and retention rates varied among the 11 included studies. In general, patients in mountainous provinces had lower adherence and retention rates than those in big cities. Retention rates decreased with the studies' follow-up period and had a downward trend over time. Factors associated with adherence and retention can be classified into three groups: individual, community, and institutional factors. Important individual factors areage, education, awareness of MMT and HIV, and co-occurring disorders and comorbidities. Stigma is the major community risk factor, and methadone daily dose, the distance between home and clinic, and clinic's service hours are the three most important institutional factors.ConclusionsThe literature reviewed identifies important factors associated with MMT adherence and retention in Vietnam. The findings suggest further research exploring both subjective and objective factors and more policies to remove social and structural barriers to enhance treatment outcomes.

BackgroundMethamphetamine (MA) use increased during COVID-19, with men who have sex with men (MSM) exhibiting 3-fold greater use than heterosexual men. Understanding links between reported MA use and COVID-19 prevention behaviors among MSM can inform current transmission risks for HIV, Monkeypox, and other infectious diseases.MethodsThis study assesses relationships between self-reported pattern of MA use (past six months; past two weeks) and reported COVID-19 preventive behaviors, adjusting for participant characteristics (HIV serostatus, race/ethnicity, employment and housing stability), in a cohort of ethnically diverse MSM in Los Angeles, California, between April 1 and September 30, 2020.ResultsCompared to those who reported no MA use, MSM who reported weekly or more MA use in the past six months were significantly less likely to use COVID-19 protective behaviors of physical distancing (61.8% vs. 81.6%; AOR = 0.39, 95% CI [0.19, 0.81]), of avoiding public transportation (34.5% vs. 60.3%; AOR = 0.42, 95% CI [0.21, 0.83]) and of avoiding traveling overall (32.7% vs. 62.6%; AOR = 0.32, 95% CI [0.16, 0.63]). Parallel findings were observed in analyses of past two-week reported MA use and COVID-19 protective behaviors.ConclusionFindings highlight ways in which reported MA use frequency links with avoidance of reported preventive behaviors for COVID-19 in urban diverse MSM. Findings also provide evidence to guide public health interventions in future outbreaks of COVID-19 and other infectious diseases among MSM.

BackgroundMethamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions, and their implementation barriers in Vietnam.MethodDesign: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions.ParticipantsWe will recruit 600 participants in 20 methadone clinics.Eligibility criteria(1) age 16+; (2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores ≥ 10 for methamphetamine use or confirmed methamphetamine use with urine drug screening; (3) willing to provide three pieces of contact information; and (4) having a cell phone.OutcomesOutcomes are measured at 13, 26, and 49 weeks and throughout the interventions. Primary outcomes include the (1) increase in HIV viral suppression, (2) reduction in HIV risk behaviors, and (3) reduction in methamphetamine use. COVID-19 response: We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity.DiscussionThis study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness.Trial registrationClinicalTrials.gov NCT04706624. Registered on 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624.

BackgroundSocial genomics has demonstrated altered inflammatory and type I interferon (IFN) gene expression among people experiencing chronic social adversity. Adverse social experiences such as discrimination and violence are linked to stimulant misuse and HIV, conditions that dysregulate inflammatory and innate antiviral responses, leading to increased HIV viral replication and risk of chronic diseases.PurposeWe aimed to determine whether methamphetamine (MA) use, unsuppressed HIV viral load (VL) (≥200 c/mL), and experienced intimate partner violence (IPV) (past 12 months) predicted inflammatory and type I IFN gene expression in HIV-positive Black and Latinx men who have sex with men (MSM).MethodsParticipants were 147 HIV-positive Black and Latinx MSM recruited from the mSTUDY, a cohort of 561 MSM aged 18-45 in Los Angeles, CA, of whom half are HIV-positive and substance-using. Transcriptomic measures of inflammatory and type I IFN activity were derived from RNA sequencing of peripheral blood mononuclear cells and matched to urine drug tests, VL, and survey data across two time points 12 months apart. Analysis used linear random intercept modeling of MA use, unsuppressed VL, and experienced IPV on inflammatory and type I IFN expression.ResultsIn adjusted models, MA use predicted 27% upregulated inflammatory and 31% upregulated type I IFN expression; unsuppressed VL predicted 84% upregulated type I IFN but not inflammatory expression; and experienced IPV predicted 31% upregulated inflammatory and 26% upregulated type I IFN expression.ConclusionsIn Black and Latinx MSM with HIV, MA use, unsuppressed VL, and experienced IPV predicted upregulated social genomic markers of immune functioning.

BackgroundPreliminary evidence indicates that acute and chronic psychological stress affect sexual arousal and satisfaction. African American women, in particular, are vulnerable to the impacts of gender- and race-related stress, given their socially constructed identities as African Americans and as women.AimWe examined associations between minority stress and sexual function using data from 248 African American women.MethodsSurveys were conducted with 248 African American women in South LA with male partners at risk for acquiring HIV. We analyzed self-reports on (i) stress indicators: chronic burden, perceived racism/sexism, and histories of trauma/sexual abuse; (ii) Female Sexual Function Index domains: desire, arousal, and satisfaction; and (iii) potential moderators: social support and spirituality. We used multiple regression, adjusting for potential confounding factors, to examine the relationships between stress indictors, potential moderators, and sexual function domains.OutcomesThe outcomes were the female sexual function index domains of desire, arousal, and satisfaction.ResultsThis largely low-income sample experienced significant chronic and acute stressors, was highly spiritual and reported strong social support. Moderate-high chronic burden and increasing sexism scores were independently associated with decreased arousal (B = -0.38, 95%CI = -0.75, -0.02) and satisfaction (B = -0.03, 95%CI = -0.06, 0.00) scores, respectively.Clinical implicationsProviders may want to explore chronic burden in patients who complain about low sexual arousal. Additionally, to develop effective HIV- and other STI-related interventions that impact behaviors that can confer sexual risk, prevention strategies are needed that either reduce contextual stressors or mitigate their impact.StrengthsStrengths of this research are that it focuses on sexual function among previously under-studied, low-income African American women and that it takes into account the unique set of stressors faced by these women.LimitationsA limitation is that the sample size may have been too small to capture the effects of potential moderators.ConclusionsLow-income African American women accumulate life stressors that may harm sexual function. Schrode K, Poareo E, Li M, et al. Minority Stress and Sexual Functioning Among African American Women With At-Risk Partners in South Los Angeles. J Sex Med 2022;19:603-612.

ObjectiveThis study tested the hypothesis that reported frequency of methamphetamine use is significantly associated with measures of social adversity, sexual risk behaviors, chronic health conditions, bacterial STIs and HIV-related factors among diverse men who have sex with men (MSM).MethodsData were 2428 visits from 515 mSTUDY participants (261 people living with HIV; 254 HIV-negative). mSTUDY is an ongoing longitudinal study of racially/ethnically diverse MSM in Los Angeles County. Logistic regression with random intercepts modeled associations between self-reported past 6-month methamphetamine use (none, monthly or less, weekly or more) with reported adverse social outcomes (unemployment, housing instability, intimate partner violence), sexual risk behaviors, chronic health conditions, and biomarkers of bacterial STIs (chlamydia, gonorrhea, or syphilis) and detectable HIV viral load (among HIV-positive). Models controlled for confirmed HIV-serostatus.ResultsPrevalence of reported monthly or less methamphetamine use was 19%; weekly or more use was 18%. Multivariable models showed escalating odds of adverse social outcomes and sexual risk behaviors (p's

Polygonum multiflorum, a species of flowering plant in the buckwheat family, is widely used in alternative medicine. However, a growing body of literature has implicated P. multiflorum as a cause of drug-induced liver injury. We report a case of successful treatment of a drug-induced liver injury after consumption of an herbal tea containing P. multiflorum.

ObjectivesTo assess the severity of methamphetamine use among methadone maintenance treatment (MMT) patients in Vietnam with opioid use disorder and concurrent methamphetamine use, and to identify risk factors associated with higher severity of methamphetamine use.MethodsWe used survey data and medical record abstractions from 428 people with opioid use disorder who also use methamphetamine while partaking in methadone treatment in five clinics in Hanoi, Vietnam. We used multinomial logistic regression to assess other risk factors and problems associated with high methamphetamine use severity.ResultsThose who reported injecting heroin in the past 3 months (AOR = 4.05, 95% CI [1.30, 12.55], p = 0.02), having a longer history of lifetime heroin use (AOR = 1.13, 95% CI [1.03, 1.24], p

AbstractThe goals and strategies of Black sexual minority men living with HIV (BSMMLWH) who achieve viral suppression require further investigation. This study explored treatment adherence strategies among BSMMLWH with sustained viral suppression. We conducted 27 in-depth qualitative interviews with BSMMLWH in Baltimore, Maryland, and Los Angeles, California, between December 2018 and May 2019. Interviews included questions guided by Positive Deviance and Life Course theoretical frameworks regarding multilevel factors and explicit strategies for antiretroviral therapy adherence. Themes regarding intentional, age group-specific strategies such as using technology (among younger men) and taking HIV medications with other daily pills (among older men) were identified. Participants also reported symbiotic goals and values that encouraged adherence, such as having a desire to live, strong familial relationships with clinicians, and support networks. Identifying personal goals and having supportive clinical and social relationships could be key to improving treatment adherence and viral suppression among BSMMLWH.

Background: Methamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a Type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions and their implementation barriers in Vietnam. Method: Design: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions. Participants We will recruit 600 participants in 20 methadone clinics. Eligibility criteria: 1) age 16+, 2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores 10 or more for methamphetamine use or confirmed methamphetamine use with urine drug screening; 3) willing to provide three pieces of contact information; 4) having a cell phone. Outcomes Outcomes are measured at 13-, 26- and 49-week and throughout the interventions. Primary outcomes include: (1) increase in HIV viral suppression; (2) reduction in HIV risk behaviors; and (3) reduction in methamphetamine use. COVID-19 response We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity. Discussion: This study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness. Trial registration NCT04706624. Registered 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624

Mindfulness-based interventions (MBIs) may offer a means for Latinx families to ameliorate stress, enhance emotion regulation, and foster social support. We assessed pilot data from Latinx parents in Eastside Los Angeles (n = 27) matched with their children aged 10-16 (n = 32) to determine whether participation in a community-derived MBI was associated with greater improvements in dispositional mindfulness, perceived stress, emotion regulation, and family social support compared to a control condition. Compared to the control group, parents in the MBI group showed greater reductions in perceived stress scale (PSS) scores (B =  - 2.94, 95% CI [- 5.58, - 0.39], p = 0.029), while their children reported greater increases in perceived social support from family (B = 2.32, 95% CI [0.26, 4.38], p = 0.027). Findings show a community-derived MBI may improve stress in Latinx parents and social support for their children.

ObjectiveTo understand the relationship between drug use, food insecurity (FI) and mental health among men who have sex with men (MSM).DesignCohort study (2014-2019) with at least one follow-up.SettingVisits at 6-month intervals included self-assessment for FI and depressive symptoms. Urine testing results confirmed drug use. Factors associated with FI were assessed using multiple logistic regression with random effects for repeated measures. General structural equation modelling tested whether FI mediates the relationship between drug use and depressive symptoms.ParticipantsData were from HIV-positive and high-risk HIV-negative MSM in Los Angeles, CA (n 431; 1192 visits).ResultsAt baseline, FI was reported by 50·8 % of participants, depressive symptoms in 36·7 % and 52·7 % of urine screening tests were positive for drugs (i.e. marijuana, opioids, methamphetamine, cocaine and ecstasy). A positive drug test was associated with a 96 % increase in the odds of being food insecure (95 % CI 1·26, 3·07). Compared to those with high food security, individuals with very low food security have a nearly sevenfold increase in the odds of reporting depressive symptoms (95 % CI 3·71, 11·92). Findings showed 14·9 % of the association between drug use (exposure) and depressive symptoms (outcome) can be explained by FI (mediator).ConclusionThe prevalence of FI among this cohort of HIV-positive and high-risk HIV-negative MSM was high; the association between drug use and depressive symptoms was partially mediated by FI. Findings suggest that enhancing access to food and nutrition may improve mood in the context of drug use, especially among MSM at risk for HIV transmission.

Background & aimsChronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19).MethodsWe conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD.ResultsOf the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19.ConclusionsThe risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.

Biological constraints in diseased tissues have motivated the need for small nanocarriers (10-30 nm) to achieve sufficient vascular extravasation and pervasive tumor penetration. This particle size limit is only an order of magnitude larger than small molecules, such that cargo loading is better described by co-assembly processes rather than simple encapsulation. Understanding the structural, kinetic, and energetic contributions of carrier-cargo co-assembly is thus critical to achieve molecular-level control towards predictable in vivo behavior. These interconnected set of properties were systematically examined using sub-20 nm self-assembled nanocarriers known as three-helix micelles (3HM). Both hydrophobicity and the "geometric packing parameter" dictate small molecule compatibility with 3HM's alkyl tail core. Planar obelisk-like apomorphine and doxorubicin (DOX) molecules intercalated well within the 3HM core and near the core-shell interface, forming an integral component to the co-assembly, as corroborated by small-angle X-ray and neutron-scattering structural studies. DOX promoted crystalline alkyl tail ordering, which significantly increased (+63%) the activation energy of 3HM subunit exchange. Subsequently, 3HM-DOX displayed slow-release kinetics (t1/2 = 40 h) at physiological temperatures, with ~50× greater cargo preference for the micelle core as described by two drug partitioning coefficients (micellar core/shell Kp1 ~ 24, and shell/bulk solvent Kp2 ~ 2). The geometric and energetic insights between nanocarrier and their small molecule cargos developed here will aid in broader efforts to deconvolute the interconnected properties of carrier-drug co-assemblies. Adding this knowledge to pharmacological and immunological explorations will expand our understanding of nanomedicine behavior throughout all the physical and in vivo processes they are intended to encounter.

Background and aimsCoronavirus disease 2019 (COVID-19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID-19 are open for study.Approach and resultsWe conducted a multicenter study in the United States of 112 adult LT recipients with COVID-19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID-19 showed moderate liver injury (ALT 2-5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT > 5× ULN) in 12.3% (n = 10). Compared to age- and sex-matched nontransplant patients with chronic liver disease and COVID-19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age (P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), Hispanic ethnicity (P = 0.011; OR, 6.01; 95% CI, 1.51-23.9), metabolic syndrome (P = 0.016; OR, 5.87; 95% CI, 1.38-24.99), vasopressor use (P = 0.018; OR, 7.34; 95% CI, 1.39-38.52), and antibiotic use (P = 0.046; OR, 6.93; 95% CI, 1.04-46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury (P = 0.156) or mortality (P = 0.084). Liver injury during COVID-19 was significantly associated with mortality (P = 0.007; OR, 6.91; 95% CI, 1.68-28.48) and ICU admission (P = 0.007; OR, 7.93; 95% CI, 1.75-35.69) in LT recipients.ConclusionsLiver injury is associated with higher mortality and ICU admission in LT recipients with COVID-19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID-19 did not increase risk for mortality or graft failure.

The effectiveness of pre-exposure prophylaxis (PrEP) against HIV acquisition depends on treatment adherence; however, within-person associations between levels of PrEP adherence and engagement in condomless sex have not been well studied. In the context of a demonstration project, 372 men who have sex with men received once-daily PrEP and completed six study visits over 48 weeks. Two-part growth mixture modeling was used to examine the longitudinal trajectory of condomless anal intercourse (CAI) and self-reports of PrEP adherence, controlling for relevant covariates. Over time, greater PrEP adherence was contemporaneously associated with both a higher likelihood of engaging in any CAI and with a greater number of CAI acts. Substance use was also associated with a higher likelihood of engaging in CAI. Contemporaneous associations between self-reported PrEP adherence and CAI suggest that adherence behaviors may be motivated by the desire to mitigate risk of HIV infection; however, exact directionality is unknown.

We assessed whether disclosure of HIV status is significantly associated with reported HIV sexual risk behaviors among HIV positive Black/African American men who have sex with men (MSM) (Black MSM) in six cities in the USA. Participants from the BROTHERS (HIV Prevention Trials Network [HPTN 061]) study focused on assessing the feasibility and acceptability of a multifaceted HIV prevention intervention to reduce HIV infections among Black MSM enrolled between July 2009 and October 2010. All participants completed a behavioral assessment using an audio computer-assisted self-interview that included questions about HIV status disclosure, HIV sexual risk behaviors, and other behaviors. Biological samples were also collected. This analysis focused on baseline data of HIV-positive Black MSM in the HPTN 061 study. Of the 143 HIV-positive Black MSM (majority ≥ 35 years of age) included in this analysis, 58% reported disclosing their HIV status to their last male anal sex partner. Forty-three percent and 42% reported condomless insertive and receptive anal intercourse respectively with their last male partner; whereas, 17% and 18% of the sample engaged in condomless insertive and receptive anal intercourse with a serodiscordant/unknown status partner, respectively. In multivariable logistic regression models, there was no statistically significant association between HIV status disclosure and condomless insertive anal intercourse (aOR = 0.35, 95% CI 0.11, 1.08; p = 0.30), condomless receptive anal intercourse (aOR = 2.48, 95% CI 0.94, 6.52; p = 0.20), or condomless receptive anal intercourse with a serodiscordant/unknown status partner (aOR = 0.55, 95% CI 0.20, 1.49; p = 0.45). However, HIV status disclosure was significantly associated with lower odds of reporting condomless insertive anal intercourse with a serodiscordant/unknown status partner (aOR = 0.19, 95% CI 0.06, 0.68; p ≤ 0.01). Among this multi-city sample of HIV-positive Black MSM, disclosure of HIV status was common and associated with lower HIV sexual risk behaviors. These findings should motivate and guide research to develop prevention messages to increase HIV status disclosures.

BackgroundIn March of 2013, the Los Angeles County (LAC) Division of HIV and STD Programs implemented a clinic-based Medical Care Coordination (MCC) Program to increase viral suppression (VS) (

IntroductionMarijuana use is common among persons living with HIV, but whether it's use increases the risk of type 2 diabetes in this population has not been explored.ObjectiveTo determine whether self-reported marijuana use is associated with incident type 2 diabetes in women and men living with and at risk for HIV.MethodsWe analyzed data from the Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS), between 2000-2017 (WIHS) and 1999-2017 MACS. The association between self-reported marijuana use and incident type 2 diabetes was analyzed using time-dependent Cox regression models among 3578 and 2682 participants in the WIHS and MACS respectively.ResultsOver the follow-up period, 452 (WIHS) and 326 (MACS) incident type 2 diabetes cases occurred. In multivariable models, the hazard ratios, collectively indicate a reduced risk of type 2 diabetes, in marijuana users compared to none users, although all associations were not statistically significant. The results were similar for HIV-positive and HIV-negative participants in both cohorts.ConclusionsIn this prospective analysis of nearly 20 years of data for women and men with and at risk for HIV in the WIHS and MACS, although we found a pattern of reduced risk of type 2 diabetes among self-reported marijuana users, the associations were not statistically significant. To better inform clinical decisions and legal policy regarding marijuana use in this population, further longitudinal investigations that biologically quantify marijuana use to assess risk for incident diabetes is warranted.

Men who have sex with men (MSM) experience high rates of homophobic victimization, which is linked to myriad chronic physical and mental health disparities. Social adversity such as rejection, isolation, and racial discrimination can induce a conserved transcriptional response to adversity (CTRA) involving upregulation of proinflammatory genes and downregulation of type I interferon and antibody synthesis genes. This study specifically examines whether homophobic victimization is associated with expression of CTRA profiles in Black and Latino MSM living in Los Angeles. Analyses linked behavioral survey data with quantified RNA from leukocytes from blood samples of 70 participants over 12 months. CTRA gene expression was increased by 3.1-fold in MSM who experienced homophobic victimization while adjusting for major leukocyte subsets and sociodemographics. Accounting for all these factors, CTRA gene expression was significantly enhanced in MSM who identified as Black compared to Latino. Our findings identify experiences of homophobic victimization as drivers of inflammatory and type I interferon gene expression profiles, which can contribute to physical and mental health challenges in Black and Latino MSM.

BackgroundPreclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α.ObjectiveThe present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients.MethodsThis trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation-sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D-by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion.ResultsWhile on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion.ConclusionsOur findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder.

BackgroundThe long-term effects of marijuana on cognition, particularly in the context of HIV is not clear, as extant research shows mixed findings.ObjectiveTo determine associations between current and cumulative exposure to marijuana and changes in cognitive processing speed and flexibility in 788 HIV-seropositive (HIV+) and 1,132 HIV-seronegative (HIV-) men followed for up to 17 years in the Multicenter AIDS Cohort Study.ResultsAmong HIV+ men only, current daily marijuana use compared to none-use, was significantly associated with a greater annual percentage decline in cognitive processing speed assessed with the Trail Making Test A (TMTA) (β=-0.41, 95% confidence interval (CI): -0.88, -0.03, p=0.03)] and Symbol Digit Modalities Test (SDMT) (β= -0.14, 95% CI: -0.28, -0.01, p=0.04). Further, monthly marijuana use was associated with greater annual percentage decline in cognitive flexibility assessed with the Trail Making Test B (TMTB) (β= -0.70, 95% CI: -1.34, -0.05; p=0.03] and cognitive processing speed (SDMT) (β= -0.21, 95% CI: -0.40, -0.01, p=0.03). Among the HIV- men only, each 5-marijuana use-years (equivalent to 5-years of daily marijuana use) was significantly associated with a 0.17 annual percentage decline in cognitive processing speed only (TMTA) (β= -0.18, 95% CI: -0.36, -0.01; p=0.04).ConclusionsOur findings suggest that marijuana use, particularly current use, may be associated with worse cognitive processing speed, but the magnitude of the estimates was not clinically meaningful.

BackgroundMen who have sex with men with histories of homophobic victimization bear heightened risk of unstable housing and methamphetamine use. However, it is unclear whether unstable housing explains the link between homophobic victimization and methamphetamine use in this group. The present study aims to test associations between homophobic victimization, unstable housing, and recent methamphetamine use across 24 months in a cohort of men of color who have sex with men (MoCSM).MethodsOur analysis stems from data of 1342 person-visits from 401 MoCSM participating in an ongoing cohort study. We performed a lagged multilevel negative binominal regression to test the association between past homophobic victimization and recent unstable housing, and a lagged multilevel ordered logistic regression to test the association between past homophobic victimization recent methamphetamine use. We then performed a path analysis to test whether recent unstable housing mediates the association between past homophobic victimization and recent methamphetamine use.ResultsFindings showed homophobic victimization associated significantly with increased odds of unstable housing (IRR = 1.70, 95% CI [1.35, 2.14], p

The aim of this analysis was to test if changes in insomnia symptoms and global sleep quality are associated with coinciding changes in depressed mood among older adults. We report on results yielded from secondary analysis of longitudinal data from a clinical trial of older adults (N = 49) aged 55 to 80 years who reported at least moderate levels of sleep problems. All measures were collected at baseline and after the trial ten weeks later. We computed change scores for two separate measures of disturbed sleep, the Athens Insomnia Scale (AIS) and the Pittsburgh Sleep Quality Index (PSQI), and tested their association with change in depressed mood (Beck Depression Inventory-II; BDI-II) in two separate linear regression models adjusted for biological covariates related to sleep (sex, age, body mass index, and NF-κB as a biological marker previously correlated with insomnia and depression). Change in AIS scores was associated with change in BDI-II scores (β = 0.38, p < 0.01). Change in PSQI scores was not significantly associated with change in BDI-II scores (β = 0.17, p = 0.26). Our findings suggest that improvements over ten weeks in insomnia symptoms rather than global sleep quality coincide with improvement in depressed mood among older adults.

African-American men who have sex with men and women (MSMW) are among those most heavily impacted by HIV in the United States, and those who have histories of incarceration are at further risk of infection. The Men in Life Environments (MILE) HIV prevention intervention was developed to provide culturally appropriate skills-based education and support for African-American MSMW with recent histories of incarceration. The MILE's conceptual framework was informed by three theories: Theory of Reasoned Action and Planned Behavior, Critical Thinking and Cultural Affirmation Model, and Empowerment Theory. The theory-based framework posits that improving racial pride is crucial in building self-efficacy and intentions that in turn promote health-protective behaviors. Therefore, our study aimed to assess whether baseline associations between racial pride and condom use self-efficacy, intentions, and behaviors among African-American MSMW with histories of incarceration align with our conceptual model. We report data on 212 participants recruited from Los Angeles County Sheriff's Department Men's Central Jail and the local community. Using structural equation modeling, we tested two separate models: one with female sexual partners and one with male sexual partners, while stratifying by participant's HIV status. Only among HIV-negative participants was greater racial pride associated with less condomless intercourse with men. In this group, greater self-efficacy and intentions-but not racial pride-predicted less condomless intercourse with women. Our findings suggest that racial pride is an important factor to address in HIV prevention interventions for post-incarcerated African-American MSMW.

Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is believed to be an essential cofactor for all living organisms1,2. Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb)3. Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes4, and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms.

Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is believed to be an essential cofactor for all living organisms1,2. Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb)3. Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes4, and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms.

ImportanceBlepharoplasty is one of the most commonly performed facial aesthetic surgeries. While myriad techniques exist to improve the appearance of the lower eyelids, there is no clear consensus on the optimal management of the orbital septum.ObjectivesTo evaluate the safety and feasibility of the use of the holmium:yttrium aluminum garnet (Ho:YAG) laser for orbital septal tightening, and to determine whether modest use of this laser would provide some degree of clinical efficacy.Design, setting, and participantsDirect laser irradiation of ex vivo bovine tissue was used to determine appropriate laser dosimetry using infrared thermal imaging and optical coherence tomography before conducting a pilot clinical study in 5 patients. Laser irradiation of the lower eyelid orbital septum was performed through a transconjunctival approach. Standardized preoperative and postoperative photographs were taken for each patient and evaluated by 6 unbiased aesthetic surgeons.ExposureUse of the Ho:YAG laser for orbital septal tightening.Main outcome and measureTo determine appropriate laser dosimetry, infrared thermal imaging and optical coherence tomography were used to monitor temperature and tissue shape changes of ex vivo bovine tissue that was subjected to direct laser irradiation. For the clinical study, preoperative and postoperative photographs were evaluated by 6 surgeons on a 10-point Likert scale.ResultsOptical coherence tomography demonstrated that laser irradiation of bovine tissue to a temperature range of 60°C to 80°C resulted in an increase in thickness of up to 2-fold. There were no complications or adverse cosmetic outcomes in the patient study. Patient satisfaction with the results of surgery averaged 7 on a 10-point Likert scale. For 3 patients, 3 (50%) of the evaluators believed there was a mild improvement in appearance of the lower eyelids after surgery. The remaining patients were thought to have no significant changes.Conclusions and relevanceTransconjunctival Ho:YAG laser blepharoplasty is a safe procedure that may ameliorate mild pseudoherniation of lower eyelid orbital fat and is a first step toward the development of percutaneous techniques.

ImportanceBlepharoplasty is one of the most commonly performed facial aesthetic surgeries. While myriad techniques exist to improve the appearance of the lower eyelids, there is no clear consensus on the optimal management of the orbital septum.ObjectivesTo evaluate the safety and feasibility of the use of the holmium:yttrium aluminum garnet (Ho:YAG) laser for orbital septal tightening, and to determine whether modest use of this laser would provide some degree of clinical efficacy.Design, setting, and participantsDirect laser irradiation of ex vivo bovine tissue was used to determine appropriate laser dosimetry using infrared thermal imaging and optical coherence tomography before conducting a pilot clinical study in 5 patients. Laser irradiation of the lower eyelid orbital septum was performed through a transconjunctival approach. Standardized preoperative and postoperative photographs were taken for each patient and evaluated by 6 unbiased aesthetic surgeons.ExposureUse of the Ho:YAG laser for orbital septal tightening.Main outcome and measureTo determine appropriate laser dosimetry, infrared thermal imaging and optical coherence tomography were used to monitor temperature and tissue shape changes of ex vivo bovine tissue that was subjected to direct laser irradiation. For the clinical study, preoperative and postoperative photographs were evaluated by 6 surgeons on a 10-point Likert scale.ResultsOptical coherence tomography demonstrated that laser irradiation of bovine tissue to a temperature range of 60°C to 80°C resulted in an increase in thickness of up to 2-fold. There were no complications or adverse cosmetic outcomes in the patient study. Patient satisfaction with the results of surgery averaged 7 on a 10-point Likert scale. For 3 patients, 3 (50%) of the evaluators believed there was a mild improvement in appearance of the lower eyelids after surgery. The remaining patients were thought to have no significant changes.Conclusions and relevanceTransconjunctival Ho:YAG laser blepharoplasty is a safe procedure that may ameliorate mild pseudoherniation of lower eyelid orbital fat and is a first step toward the development of percutaneous techniques.

Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). It is characterized by the infiltration of autoreactive immune cells into the CNS, which target the myelin sheath, leading to the loss of neuronal function. Although it is accepted that MS is a multifactorial disorder with both genetic and environmental factors influencing its development and course, the molecular pathogenesis of MS has not yet been fully elucidated. Here, we studied the longitudinal gene expression profiles of whole-blood RNA from a cohort of 195 MS patients and 66 healthy controls. We analyzed these transcriptomes at both the individual transcript and the biological pathway level. We found 62 transcripts to be significantly up-regulated in MS patients; the expression of 11 of these genes was counter-regulated by interferon treatment, suggesting partial restoration of a 'healthy' gene expression profile. Global pathway analyses linked the proteasome and Wnt signaling to MS disease processes. Since genotypes from a subset of individuals were available, we were able to identify expression quantitative trait loci (eQTL), a number of which involved two genes of the MS gene signature. However, all these eQTL were also present in healthy controls. This study highlights the challenge posed by analyzing transcripts from whole blood and how these can be mitigated by using large, well-characterized cohorts of patients with longitudinal follow-up and multi-modality measurements.

ObjectiveHippocampal demyelination, a common feature of postmortem multiple sclerosis (MS) brains, reduces neuronal gene expression and is a likely contributor to the memory impairment that is found in >40% of individuals with MS. How demyelination alters neuronal gene expression is unknown.MethodsTo explore whether loss of hippocampal myelin alters expression of neuronal microRNAs (miRNAs), we compared miRNA profiles from myelinated and demyelinated hippocampi from postmortem MS brains and performed validation studies.ResultsA network-based interaction analysis depicts a correlation between increased neuronal miRNAs and decreased neuronal genes identified in our previous study. The neuronal miRNA miR-124 was increased in demyelinated MS hippocampi and targets mRNAs encoding 26 neuronal proteins that were decreased in demyelinated hippocampus, including the ionotrophic glutamate receptors AMPA2 and AMPA3. Hippocampal demyelination in mice also increased miR-124, reduced expression of AMPA receptors, and decreased memory performance in water maze tests. Remyelination of the mouse hippocampus reversed these changes.InterpretationWe establish here that myelin alters neuronal gene expression and function by modulating the levels of the neuronal miRNA miR-124. Inhibition of miR-124 in hippocampal neurons may provide a therapeutic approach to improve memory performance in MS patients.

Electromechanical reshaping (EMR) of cartilage is a novel technique that has significant potential for use in facial reconstructive surgery. EMR achieves permanent shape change by initiating electrochemical redox reactions in the vicinity of stress concentrations, thereby altering mechanical properties of tissue matrix. This study reports the use of a six electrode needle-based geometric configuration to reshape cartilage. Rectangular samples (24 × 12 × 1 mm) of rabbit nasal septal cartilages were bent at a right angle in a precision-machined reshaping jig. Two parallel arrays of three platinum needle electrodes were each inserted into cartilage along the bend at 3 mm from the bend line. One array served as an anode and the other as cathode. Constant voltage at 1, 2, 4, 6, and 8 volts was applied to the arrays for 2 minutes. The specimens were then removed from the jig and rehydrated for 15 minutes in phosphate buffered saline. Following rehydration, bend angles and thicknesses were measured. Bend angle increased with increasing voltage and application time. No statistically significant bending was observed below 6 volts for 2 minutes application time. Maximum bend angle of 33 ± 8 degrees or reshaping degree of 33% was observed at 8 volts applied for 2 minutes. Current flow was small (< 0.1 A) for each case. Sample thickness was 0.9 ± 0.2 mm. ANOVA analysis showed that cartilage thickness had no significant impact on the extent of reshaping at given voltage and application time. The six needle electrode geometric configuration conforms to the voltage- and time-dependent trends predicted by previous EMR studies. In the future, the reshaping properties of other geometric configurations will be explored. © 2009 SPIE.