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OBJECTIVE: This study assesses the impact of a school-based drug prevention program, called Project ALERT, on risky sexual behavior among 1901 nonmarried, sexually active young adults who participated in one of two program variations as adolescents. It also tests for differences in program effect depending on program duration (middle school only vs. a combined middle school and high school program) and participants' gender. METHODS: Using survey data from a randomized controlled experiment conducted in 45 midwestern communities (55 schools), we assessed program effects on risky sexual behavior at age 21 with three measures-having unprotected sex because of drug use plus engaging in inconsistent condom use and having sex with multiple partners. RESULTS: Compared to control, Project ALERT reduced the likelihood of all risky sex outcomes except inconsistent condom use among these sexually active young adults, effects that occurred 5 and 7 years after program exposure. Program effects were partially mediated by reductions in alcohol and drug abuse. There were no significant differences in program effects by gender or by program duration compared to control. Implications for future prevention programs and research are discussed. [ABSTRACT FROM AUTHOR]

The current ethical structure for collaborative international health research stems largely from developed countries' standards of proper ethical practices. The result is that ethical committees in developing countries are required to adhere to standards that might impose practices that conflict with local culture and unintended interpretations of ethics, treatments, and research. This paper presents a case example of a joint international research project that successfully established inclusive ethical review processes as well as other groundwork and components necessary for the conduct of human behavior research and research capacity building in the host country. [ABSTRACT FROM AUTHOR]

Context: In 2004, California's Paid Family Leave Insurance Program (PFLI) became the first state program to provide paid leave to care for an ill family member.Objective: To assess awareness and use of the program by employed parents of children with special health care needs, a population likely to need leave.Design, Setting, and Participants: Telephone interviews with successive cohorts of employed parents before (November 21, 2003-January 31, 2004; n = 754) and after (November 18, 2005-January 31, 2006; n = 766) PFLI began, randomly sampled from 2 children's hospitals, one in California (with PFLI) and the other in Illinois (without PFLI). Response rates were 82% before and 81% after (California), and 80% before and 74% after (Illinois).Main Outcome Measures: Taking leave, length of leave, unmet need for leave, and awareness and use of PFLI.Results: Similar percentages of parents at the California site reported taking at least 1 day of leave to care for their ill child before (295 [81%]) and after (327 [79%]) PFLI, taking at least 4 weeks before (64 [21%]) and after (74 [19%]) PFLI, and at least once in the past year not missing work despite believing their child's illness necessitated it before (152 [41%]) and after (156 [41%]) PFLI. Relative to Illinois, parents at the California site reported no change from before to after PFLI in taking at least 1 day of leave (difference of differences, -3%; 95% confidence interval [CI], -13% to 7%); taking at least 4 weeks of leave (1%; 95% CI, -9% to 10%); or not missing work, despite believing their child's illness necessitated it (-1%; 95% CI, -13% to 10%). Only 77 parents (18%) had heard of PFLI approximately 18 months after the program began, and only 20 (5%) had used it. Even among parents without other access to paid leave, awareness and use of PFLI were minimal.Conclusions: Parents of children with special health care needs receiving care at a California hospital were generally unaware of PFLI and rarely used it. Among parents of children with special health care needs, taking leave in California did not increase after PFLI implementation compared with Illinois. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study examined the rates and correlates of out-of-network outpatient mental health specialty care. RESEARCH DESIGN: Using administrative data from a large insurer, we examine the frequency of out-of-network utilization, analyze demographic and clinical characteristics of individuals receiving out-of-network care, and examine the types of service provided out-of-network. RESULTS: Out-of-network outpatient mental health care was received by 15.4% of adults who used outpatient mental health services, with 11.8% of adult outpatient mental health users receiving only out-of-network care and 3.6% receiving both in-network and out-of-network care. Out-of-network users received significantly more outpatient mental health care than individuals receiving only in-network mental health care. Rates of out-of-network psychotherapy services were substantially greater than for other commonly provided mental health services. CONCLUSION: A significant number of patients covered under this insurer received their outpatient mental health care out-of-network. This is most pronounced for individuals receiving psychotherapy. Further information is needed to improve our understanding of who seeks care from out-of-network providers and why as well as the effect of such care on clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Second-generation, or atypical, antipsychotics effectively treat psychiatric illness in children and adolescents. However, weight gain and abnormalities in insulin sensitivity, including diabetes, complicate this therapy.Method: A 16-week double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of metformin in managing weight gain in 39 subjects, ages 10-17, whose weight had increased by more than 10% during less than 1 year of olanzapine, risperidone, or quetiapine therapy. Body weight, body mass index (kilograms per square meter of height), and waist circumference were measured regularly, as were fasting insulin and glucose levels.Results: Weight was stabilized in subjects receiving metformin, while those receiving placebo continued to gain weight (0.31 kg/week). Because the study was conducted with growing children, metformin treatment resulted in reduction in z scores for both weight and body mass index. The homeostasis model assessment, a surrogate indicator of insulin sensitivity, decreased in treated subjects. Overt diabetes was diagnosed in two subjects before treatment (elevated baseline fasting glucose and insulin values) and in two placebo-treated subjects (one at week 12 and the other after study completion). One subject taking placebo developed impaired fasting glucose. Placebo treatment was associated with the need to perform oral glucose tolerance testing upon study completion, by which three additional subjects were identified with impaired glucose tolerance. No serious adverse events resulted from metformin treatment.Conclusions: Metformin therapy is safe and effective in abrogating weight gain, decreased insulin sensitivity, and abnormal glucose metabolism resulting from treatment of children and adolescents with atypicals. [ABSTRACT FROM AUTHOR]

Social control has the potential to encourage engagement in a healthy lifestyle, but its effectiveness may depend on the nature of the influence attempt. Participants (N = 282) described a situation in which someone attempted to influence their health-related behavior. Experiencing positive social control was associated with a greater tendency to change the behavior and less ignoring/doing nothing, whereas negative social control was associated with a lesser tendency to change the behavior and more hiding of unhealthy behavior. These associations could be accounted for by affective responses to the social control attempts. Results emphasize the need to better understand the regulatory influence of relationships on health behavior and the conditions under which social control is most likely to have health-promoting effects. ((c) 2006 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

PURPOSE: To identify predictors of the transition from experimentation to regular smoking in middle adolescence, late adolescence, and young adulthood. METHODS: California and Oregon students completed self-report surveys assessing the following potential predictors of the transition to regular smoking from grades 8 to 10 (n = 2,496), grades 10 to 12 (n = 2,149), and grade 12 to age 23 years (n = 1,534): demographic characteristics; smoking-related attitudes, behaviors and environment; other problem behaviors; academic orientation; parental bonding; and mental health. Huberized regression techniques, which adjust for weighting and clustering of observations, were used to determine the independent associations of the predictor variables on subsequent smoking status. RESULTS: Risk factors for the transition to regular smoking during middle adolescence included being white, prosmoking attitudes, friend smoking, weak academic orientation, and less parental support. During late adolescence, being African-American was protective, whereas risk factors included prosmoking attitudes, drinking, non-intact nuclear family, and less parental support. Risk factors in young adulthood included younger age and prosmoking attitudes. CONCLUSIONS: Results point to several smoking-related attitudes, social influences, and behaviors that prevention efforts may target to curb the escalation of smoking. [ABSTRACT FROM AUTHOR]

The purpose of this study was to apply a benchmarking methodology to identify the most effective approaches used by long-term care facilities in implementing new computerized resident assessment instrument/minimum data set (RAI/MDS) systems and to develop implementation protocols based on these "best practices." Site visits were conducted with 3 long-term care facilities, selected on the basis of a national search. Facility directors, directors of nursing, information system managers, and frontline staff at each facility were targeted, and questionnaires were developed for each to assess factors viewed as important to successful implementation. A convergence was found in recommended action steps reported across sites to facilitate introduction and implementation of new RAI/MDS software. An example of how benchmarking results were used to develop an implementation plan is provided. Benchmarking provided a useful methodology for identifying best practices to guide implementation planing for adoption of a new computerized RAI/MDS system in the current trial. The benchmarking steps described are replicable and can be used to guide implementation of other new systems in the nursing home setting. [ABSTRACT FROM AUTHOR]

Social control can positively influence health behaviors, but changes in social networks over time may cause older adults to experience less health-related social control. The size and composition of social control networks, and receipt of health-related social control, were examined in a probability sample of 509 household residents (aged 25-80 years) in Los Angeles County who completed a telephone survey. Compared with younger and middle-aged adults, older adults identified fewer people who attempted to influence their health behaviors and fewer health behaviors that others urged them to change. Older adults also reported less frequent social control attempts aimed at modifying their health behaviors, even after health status, health habits, and social network characteristics were controlled for. Possible explanations for these age-related differences are discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To provide recommendations that will build a better foundation for research on youth smoking cessation. METHODS: The Youth Tobacco Collaborative Cessation panel evaluated youth tobacco cessation literature and convened meetings to reach consensus. RESULTS: Methodological issues include design, recruitment and retention, follow-up, measurement, and youth vernacular. Research gaps include youth characteristics, theoretical approaches, delivery settings, and type of provider. Thirteen key research components for reporting are addressed. CONCLUSIONS: Given the dearth of studies on youth smoking cessation, scientifically rigorous studies need to be conducted with attention to methodological issues, research gaps, and reporting of key research components. [ABSTRACT FROM AUTHOR]

Peer advocacy can promote HIV protective behaviors, but little is known about the concordance on prevention advocacy(PA) reports between people living with HIV(PLWH) and their social network members. We examined prevalence and correlates of such concordance, and its association with the targeted HIV protective behavior of the social network member. Data were analyzed from 193 PLWH(index participants) and their 599 social network members(alters). Kappa statistics measured concordance between index and alter reports of PA in the past 3 months. Logistic and multinomial regressions evaluated the relationship between advocacy concordance and alter condom use and HIV testing behavior and correlates of PA concordance. Advocacy concordance was observed in 0.3% of index-alter dyads for PrEP discussion, 9% for condom use, 18% for HIV testing, 26% for care engagement, and 49% for antiretroviral use discussions. Fewer indexes reported condom use(23.5% vs. 28.1%;[Formula: see text]=3.7, p=0.05) and HIV testing(30.5% vs. 50.5%; [Formula: see text]=25.3, p<0.001) PA occurring. Condom advocacy concordance was higher if the index and alter were romantic partners(OR=3.50; p=0.02), and lower if the index was 10 years younger than the alter(OR=0.23; p = 0.02). Alters had higher odds of using condoms with their main partner when both reported condom advocacy compared to dyads where neither reported advocacy(OR=3.90; p<0.001) and compared to dyads where only the index reported such advocacy(OR = 3.71; p=0.01). Age difference and relationship status impact advocacy agreement, and concordant perceptions of advocacy are linked to increased HIV protective behaviors. Alters' perceptions may be crucial for behavior change, informing strategies for improving advocacy., (© 2024. The Author(s).)

Mobile populations such as fisherfolk show high HIV incidence and prevalence. We pilot-tested implementation strategies to enhance pre-exposure prophylaxis (PrEP) uptake and adherence in the context of healthcare outreach events in two mainland fisherfolk communities on Lake Victoria, Uganda from September 2021 to February 2022. The implementation strategies included PrEP adherence supporters (selected from PrEP users' social networks), community workshops (to address misconceptions and stigma, and empower PrEP advocacy), and check-in calls (including refill reminders). PrEP medical records data were collected from 6-months pre-intervention to 6-months post-intervention. Qualitative interviews with 20 PrEP users (10 who continued, 10 who discontinued), 9 adherence supporters, and 7 key partners (providers, community leaders) explored acceptability. Percentages of PrEP initiators (of those eligible) were significantly higher during the intervention (96.5%) than 6-months before the intervention (84.5%), p < 0.0001; percentages of PrEP users who persisted (i.e., possessed a refill) 6-months post-initiation (47.9% vs. 6.7%) and had at least 80% PrEP coverage (based on their medication possession ratio) from the initiation date to 6-months later (35.9% vs. 0%) were higher during versus pre-intervention, p < 0.0001. A comparison fisherfolk community with better healthcare access had lower uptake (78.3%; p < 0.0001) and persistence at 6-months (34.0%; p < 0.001), but higher coverage during the intervention period (70.4%; p < 0.0001). Qualitative data suggested the strategies promoted PrEP use through reduced stigma and misconceptions. The intervention bundle cost was $223.95, $172.98, and $94.66 for each additional person for PrEP initiation, persistence, and coverage, respectively. Enhanced community-based PrEP implementation that fosters a supportive community environment can improve PrEP use in mobile populations without easy access to healthcare. (NCT05084716)., (© 2024. The Author(s).)

Background: Low-cost, scalable strategies are necessary to reach the UNAIDS 2030 target of ending HIV as a public health threat. Use of treatment partners, informal caregivers selected by people living with HIV to support antiretroviral therapy adherence, is one such strategy that is included in many countries' HIV guidelines, including Botswana, a country with high HIV prevalence., Method: From June 2021 to June 2022, we pilot tested a clinic-based treatment partner intervention ("Mopati"), including standardized language for providers to guide patients on treatment partner selection and workshops to train treatment partners on providing non-directive support to patients using a non-confrontational, non-judgmental approach. Sixty unsuppressed patients (30 per clinic) and 45 treatment partners (17 intervention, 28 control) were recruited from an intervention-control clinic matched-pair in Gaborone, Botswana., Results: Mopati had medium-to-large effects on increasing patients' adherence, adherence self-efficacy, intrinsic adherence motivation, and perceived non-directive support from treatment partners, and decreasing treatment partner caregiver burden. Aggregate viral suppression rates significantly increased in the intervention (vs. control) clinic. Qualitative data from 14 clinic staff, 21 patients, and 16 treatment partners indicated that Mopati was viewed as effective. Providers said the guidance empowered them to be proactive in communicating about adherence; most reported using the guidance., Conclusion: This study shows preliminary support for the use of treatment partners in HIV care, and further evidence for interventions that leverage patients' existing support. This research can inform ways to improve adherence to HIV treatment as well as the treatment of HIV-related comorbid conditions in lower-resource settings., Trial Registration: ClinicalTrials.gov Identifier: NCT04796610., (© 2024. The Author(s).)

Acinetobacter baumannii , a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.

Background: While a number of tools exist to predict mortality among older adults, less research has described the characteristics of Medicare Advantage (MA) enrollees at higher risk for 1 year mortality., Objectives: To describe the characteristics of MA enrollees at higher mortality risk using patient survey data., Research Design: Retrospective cohort., Subjects: MA enrollees completing the 2019 MA Consumer Assessment of Healthcare Providers and Systems (CAHPS) Survey., Measures: Linked demographic, health, and mortality data from a sample of MA enrollees were used to predict 1-year mortality risk and describe enrollee characteristics across levels of predicted mortality risk., Results: The mortality model had a 0.80 c-statistic. Mortality risks were skewed: 6 % of enrollees had a ≥ 10 % 1-year mortality risk, while 45 % of enrollees had 1 % to < 5 % 1-year mortality risk. Among the high-risk (≥10 %) group, 47 % were age 85+ versus 12 % among those with mortality risk <5 %. 79 % were in fair or poor self-rated health versus 29 % among those with mortality risk of <5 %. 71 % reported needing urgent care in the prior 6 months versus 40 % among those with a mortality risk of 1 to<5 %., Conclusions: Relatively few older adults enrolled in MA are at high 1-year mortality risk. Nonetheless, MA enrollees over age 85, in fair or poor health, or with recent urgent care needs are far more likely to be in a high mortality risk group., Competing Interests: Declaration of competing interest The authors confirm that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Black sexual minority men (SMM) are disproportionately impacted by HIV in the United States. Intimate partner violence (IPV), substance use, and depression are associated with HIV risk behavior such as condomless sex. In this study, we assessed cross-sectional associations between multiple types of IPV victimization and condomless sex with serodiscordant partners. We then evaluated the mediating roles of mental health and substance use, in a sample of 213 Black SMM living with HIV. We used validated scales to assess IPV victimization, depression, post-traumatic stress symptoms, general mental health, and substance use. All independent variables (IPV type) that had at least a marginal ( p  < .10) association with the dependent variable (condomless sex with a serodiscordant partner) and any potential mediator were included in mediation models. Mediator role was determined based on a statistically significant outcome ( p  < .05) in the mediation model. Physical assault, injury-inducing IPV, and sexual coercion were each positively correlated with condomless sex. Depression, overall mental health, and substance use were associated with physical assault and injury-inducing IPV, and depression was associated with sexual coercion IPV. Both physical assault and injury-inducing IPV were associated with overall mental health, but none of the mental health and substance use measures mediated the associations between IPV and condomless sex. Findings suggest that HIV prevention efforts for Black SMM may need to incorporate IPV screening and prevention services. Further research is needed to understand the psychosocial pathways by which physical forms of IPV relate to condom use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background: Urban American Indian/Alaska Native (AI/AN) adolescents are vulnerable to sleep and other health-related disparities due to numerous social drivers, including historical trauma and relocation to urban areas. This study aims to identify strategies to increase protective factors and culturally tailor sleep health interventions for this population., Methods: Using community-based participatory research, the NAYSHAW study conducted in-depth interviews with urban AI/AN adolescents aged 12-19 years to understand critical components needed for developing a culturally sensitive sleep health intervention. Data from two qualitative subsamples (N = 46) and parent surveys (N = 110) were analyzed, focusing on factors that affect sleep health behaviors, including parental involvement, technology, and traditional practices., Results: Key findings include the detrimental impact of electronics use at night and protective effects of traditional practices on sleep. Parental involvement in sleep routines varied by adolescent's age. Adolescents desired sleep health education in interactive formats, whereas parents preferred workshops and digital applications for sleep health strategies. Findings suggest that interventions need to address electronics use and should also be culturally tailored to address the unique experiences of urban AI/AN adolescents., Conclusions: Results underscore the importance of utilizing community-based strategies to develop culturally tailored sleep interventions for underserved populations, specifically urban AI/AN adolescents. Integrating traditional practices with evidence-based sleep health strategies can provide a holistic approach to improving sleep and overall well-being. Parental education and involvement will be critical to the success of such interventions., (© 2024 RAND Corporation and The Authors. Journal of Adolescence published by Wiley Periodicals LLC on behalf of Foundation for Professionals in Services to Adolescents.)

Loneliness, an emerging public health problem, is higher among people living with HIV and is associated with negative health outcomes. Black/African Americans have a high burden of HIV, and little is known about the characteristics of loneliness among Black adults living with HIV; therefore, this study sought to understand the sociodemographic and psychosocial correlates of Black adults living with HIV who are lonely and the implications of loneliness for their health outcomes. A sample of 304 Black adults living with HIV (73.8% sexual minority men) in Los Angeles County, CA, USA, completed the survey items assessing sociodemographic and psychosocial characteristics, social determinants of health, health outcomes, and loneliness. Antiretroviral therapy (ART) adherence was assessed electronically with the medication event monitoring system. Bivariate linear regressions analysis showed higher loneliness scores among those with higher levels of internalized HIV stigma, depression, unmet needs, and discrimination related to HIV serostatus, race, and sexual orientation. In addition, participants who were married or living with a partner, had stable housing, and reported receiving more social support had lower levels of loneliness. In multivariable regression models controlling for correlates of loneliness, loneliness was found to be a significant independent predictor of worse general physical health, worse general mental health, and greater depression. Loneliness was marginally associated with lower ART adherence. Findings suggest that Black adults living with HIV, who experience multiple intersectional stigmas, require targeted interventions and resources., (© 2023. The Author(s).)

Objectives: Black Americans have been disproportionally affected by the HIV epidemic, and experience significant disparities in sleep health, mental health, and physical health domains. Using longitudinal data from a sample of Black adults with HIV, the current study examined the associations between stigma and mental and physical health outcomes and how sleep disturbance may play a mediating role., Methods: Data were drawn from a recent randomized controlled trial. Questionnaires were used to examine internalized and anticipated HIV stigma, perceived discrimination (enacted stigma) based on multiple social identities (i.e., HIV-serostatus, race, sexual orientation), sleep disturbance, mental health problems (depressive and posttraumatic stress disorder [PTSD] symptoms), and mental and physical health-related quality of life (HRQOL) at baseline, 7-month follow-up, and 13-month follow-up assessments. Linear mixed modeling was used to examine main effects of stigma on health outcomes; causal mediation analysis was used to estimate indirect paths through sleep disturbance., Results: Internalized and anticipated HIV stigma and multiple discrimination were associated with more sleep disturbance, more depressive and PTSD symptoms, and poorer mental and physical HRQOL. Results also indicated significant indirect paths (i.e., mediation) through greater sleep disturbance between HIV-related stigma and discrimination and mental health and health-related quality of life., Conclusions: Results support that sleep disturbance is a mediating pathway through which different forms of stigmas impact health outcomes. Sleep may be an intervention target to help improve mental and physical well-being and reduce health disparities among racial and ethnic minority people with HIV., (© 2024. The Author(s).)

Human papillomavirus (HPV) is the cause of almost all cases of cervical cancer, a disease that kills some 340,000 women per year. The timeline from initial infection with HPV to the onset of invasive cervical cancer spans decades, and observational studies of this process are limited to settings in which treatment of precancerous lesions was withheld or inadequate. Such studies have been critical for understanding the natural history of HPV. Modeling can shed additional insight on the natural history of HPV, especially across geographical settings with varying prevalence of factors known to affect the host-side immune response to HPV, such as HIV and tobacco use. In this study, we create models for the 30 most populous countries in Sub-Saharan Africa, each with country-specific demographic, and behavioral inputs. We found that it was not possible to fit the data if we assumed that the natural history parameters were exactly identical for all countries, even after accounting for demographic and behavioral differences, but that we could achieve a good fit with the addition of a single immunocompetence parameter for each country. Our results indicate that variation in host immune responses may play a role in explaining the differences in the burden of cervical cancer between countries, which in turn implies a greater need for more geographically diverse data collection to understand the natural history of HPV., (© 2024. The Author(s).)

Islatravir (ISL) is a deoxyadenosine analog that inhibits HIV-1 reverse transcription by multiple mechanisms. Lenacapavir (LEN) is a novel capsid inhibitor that inhibits HIV-1 at multiple stages throughout the viral life cycle. ISL and LEN are being investigated as once-weekly combination oral therapy for the treatment of HIV-1. Here, we characterized ISL and LEN in vitro to assess combinatorial antiviral activity, cytotoxicity, and the potential for interactions between the two compounds. Bliss analysis revealed ISL with LEN demonstrated additive inhibition of HIV-1 replication, with no evidence of antagonism across the range of concentrations tested. ISL exhibited potent antiviral activity against variants encoding known LEN resistance-associated mutations (RAMs) with or without the presence of M184V, an ISL RAM in reverse transcriptase (RT) . Static resistance selection experiments were conducted with ISL and LEN alone and in combination, initiating with either wild-type virus or virus containing the M184I RAM in RT to further assess their barrier to the emergence of resistance. The combination of ISL with LEN more effectively suppressed viral breakthrough at lower multiples of the compounds' IC 50 (half-maximal inhibitory concentration) values and fewer mutations emerged with the combination compared to either compound on its own. The known pathways for development of resistance with ISL and LEN were not altered, and no novel single mutations emerged that substantially reduced susceptibility to either compound. The lack of antagonism and cross-resistance between ISL and LEN support the ongoing evaluation of the combination for treatment of HIV-1., Competing Interests: T.L.D., S.L.G., W.N., S.R., M.X. (former), D.J.K., J.A.G. (former), and E.A.A. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), who may own stock and/or hold stock options in MSD.

Background and Objectives: Limited research has examined how discrimination in young adulthood relates to substance use. We examined how multiple and specific types (e.g., race-based) of experiences of unfair treatment are related to problematic alcohol and cannabis use., Methods: We analyzed cross-sectional data from a diverse cohort of young adults (mean age 24.7) predominantly residing in southern California (n = 2303) to examine associations of multiple (count) and specific experiences (race-, sexual orientation-, gender-based) of perceived everyday discrimination with self-reported alcohol and cannabis use outcomes (consequences, use disorders, and solitary use). We also tested interactions between the three specific discrimination experiences and sociodemographic characteristics (e.g., race-based discrimination × race/ethnicity)., Results: In this diverse sample (e.g., 47% Latinx/o and 22% Asian; 22% sexual/gender diverse; 56% female) of young adults, about 46% reported up to four different discrimination experiences and 27% reported race-, 26% gender-, and 5% sexual orientation-based discrimination. Race- and gender-based discrimination and experiencing more types of discrimination were associated with worse cannabis use outcomes. Race-based discrimination was associated with fewer alcohol consequences and lower Alcohol Use Disorders Identification Test (AUDIT) scores. Associations with sexual orientation-based discrimination and the interactions were not significant., Discussion and Conclusions: Findings build on limited research on associations of discrimination with cannabis use in young adults. More work is needed to understand the mechanisms by which discrimination influences drinking behaviors., Scientific Significance: This study advances the field by examining the unique contributions of specific and multiple types of discrimination experiences in young adulthood, a critical developmental period in which substance use peaks., (© 2024 The American Academy of Addiction Psychiatry (AAAP).)

In 2020, the WHO launched its first global strategy to accelerate the elimination of cervical cancer, outlining an ambitious set of targets for countries to achieve over the next decade. At the same time, new tools, technologies, and strategies are in the pipeline that may improve screening performance, expand the reach of prophylactic vaccines, and prevent the acquisition, persistence and progression of oncogenic HPV. Detailed mechanistic modelling can help identify the combinations of current and future strategies to combat cervical cancer. Open-source modelling tools are needed to shift the capacity for such evaluations in-country. Here, we introduce the Human papillomavirus simulator (HPVsim), a new open-source software package for creating flexible agent-based models parameterised with country-specific vital dynamics, structured sexual networks, and co-transmitting HPV genotypes. HPVsim includes a novel methodology for modelling cervical disease progression, designed to be readily adaptable to new forms of screening. The software itself is implemented in Python, has built-in tools for simulating commonly-used interventions, includes a comprehensive set of tests and documentation, and runs quickly (seconds to minutes) on a laptop. Performance is greatly enhanced by HPVsim's multiscale modelling functionality. HPVsim is open source under the MIT License and available via both the Python Package Index (via pip install) and GitHub (hpvsim.org)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stuart 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.)

Receiving peer advocacy has been shown to result in increased HIV protective behaviors, but little research has gone beyond assessment of the mere presence of advocacy to examine aspects of advocacy driving these effects. With baseline data from a controlled trial of an advocacy training intervention, we studied characteristics of HIV prevention advocacy received among 599 social network members of persons living with HIV in Uganda and the association of these characteristics with the social network members' recent HIV testing (past six months) and consistent condom use, as well as perceived influence of advocacy on these behaviors. Participants reported on receipt of advocacy specific to HIV testing and condom use, as well as on measures of advocacy content, tone of delivery, support for autonomous regulation, and perceived influence on behavior. Receiving HIV testing advocacy and condom use advocacy were associated with recent HIV testing [65.2% vs. 51.4%; OR (95% CI) = 1.77 (1.11-2.84)], and consistent condom use with main sex partner [19.3% vs. 10.0%; OR (95% CI) = 2.16 (1.12-4.13)], respectively, compared to not receiving advocacy. Among those who received condom advocacy, perceived influence of the advocacy was positively correlated with consistent condom use, regardless of type of sex partner; support of autonomous regulation was a correlate of consistent condom use with casual sex partners, while judgmental advocacy was a correlate of consistent condom use with serodiscordant main partners. Among those who received testing advocacy, HIV testing in the past 6 months was positively correlated with receipt of direct support for getting tested. In multiple regression analysis, perceived influence of both HIV testing and condom use advocacy were positively correlated with advocacy that included access information and support of autonomous regulation; confrontational advocacy and judgmental advocacy were independent positive correlates of perceived influence of testing and condom use advocacy, respectively. These findings support associations that suggest potential benefits of peer advocacy from PLWH on HIV testing and condom use among their social network members, and indicate that advocacy content, tone of delivery, and support of autonomous regulation advocacy may play an important role in the success of advocacy., (© 2024. The Author(s).)

Importance: Adolescent sleep problems are prevalent, particularly among racial and ethnic minority groups, and can increase morbidity. Despite the numerous strengths of their racial and ethnic group, urban American Indian and Alaska Native adolescents face significant health disparities but are rarely included in health research. Understanding how sleep problems are associated with health outcomes among American Indian and Alaska Native adolescents may elucidate novel targets for interventions to promote health equity., Objective: To assess whether baseline sleep problems are associated with changes in behavioral and cardiometabolic health outcomes among urban American Indian and Alaska Native adolescents 2 years later., Design, Setting, and Participants: American Indian and Alaska Native adolescents were recruited via flyers and community events for an observational cohort study in California. Baseline assessments were conducted among 142 adolescents from March 1, 2018, to March 31, 2020, and follow-ups were conducted among 114 adolescents from December 1, 2020, to June 30, 2022., Exposures: Baseline actigraphy-assessed sleep duration and efficiency and self-reported sleep disturbances and social jet lag (absolute value of the difference in sleep midpoint on weekends vs weekdays; indicator of circadian misalignment)., Main Outcomes and Measures: Main outcome measures included self-reported depression (measured using the Patient Health Questionnaire), anxiety (measured using the Generalized Anxiety Disorder 7-item scale), past year alcohol and cannabis use, body mass index, systolic blood pressure (SBP) and diastolic blood pressure (DBP), waist circumference, and glycosylated hemoglobin (HbA1c). Analyses examined whether baseline sleep was associated with health outcomes at follow-up, controlling for age, sex, and baseline outcome measures., Results: The baseline sample included 142 urban American Indian and Alaska Native adolescents (mean [SD] age, 14.0 [1.4] years; 84 girls [59%]), 80% of whom (n = 114; mean [SD] age, 14.1 [1.3] years; 71 girls [62%]) completed follow-ups. Linear or logistic regressions showed significant negative associations between shorter sleep duration and depression (β = -1.21 [95% CI, -2.19 to -0.24]), anxiety (β = -0.89 [95% CI, -1.76 to -0.03]), DBP (β = -2.03 [95% CI, -3.79 to -0.28]), and HbA1c level (β = -0.15 [95% CI, -0.26 to -0.04]) and likelihood of alcohol (odds ratio [OR], 0.57 [95% CI, 0.36-0.91]) and cannabis use (full week: OR, 0.59 [95% CI, 0.35-0.99]) at follow-up. Greater social jet lag was associated with significantly higher SBP (β = 0.06 [95% CI, 0.01-0.11]) at follow-up., Conclusions and Relevance: This cohort study found significant associations between poor sleep and adverse changes in health outcomes. Findings highlight the importance of developing culturally responsive interventions that target sleep as a key modifiable risk factor to improve the health of American Indian and Alaska Native adolescents.

Young adults experiencing homelessness (YAEH) are faced with instabilities in many areas of their lives, including their living situation, employment, and income. Little is known about how the experience of instability in these different domains might be associated with substance use. Leveraging data collected on 276 YAEH in Los Angeles County, regression analyses examine associations between three distinct types of instability (housing, employment, income) and participants' self-reported alcohol use, alcohol consequences, non-cannabis drug use, and substance use symptoms. Results indicated that recent instability in income, employment, and secure housing for those with access to it (but not housing in general or non-secure housing) were significantly associated with greater alcohol/drug use or substance use symptoms. Depression was also found to moderate the association between employment instability and alcohol use. Our findings suggest that efforts to reduce instability in income, employment, and secure housing may have positive benefits for substance using YAEH, especially those with depressive symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jose 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.)

Objective: Despite rates of alcohol misuse being higher among emerging adults experiencing homelessness compared to those who are stably housed, there are few brief evidence-based risk reduction programs for this population that focus on alcohol use and assess outcomes for more than 1 year. This study examines alcohol outcomes from a 24-month evaluation of AWARE, a brief motivational interviewing-based group risk reduction intervention for emerging adults experiencing homelessness., Method: In a cluster randomized crossover trial, 18- to 25- year-olds received AWARE ( n = 132) or standard care ( n = 144) at one of three drop-in centers serving young people experiencing homelessness in Los Angeles County. We evaluated intervention effects on past month alcohol use, consequences, and related cognitions such as motivation to change behavior., Results: AWARE participants showed significant reductions over 24 months in alcohol use and negative consequences from drinking and reported significant increases in their use of drinking protective strategies. Except for drinking frequency, control group participants did not show a significant change in these outcomes., Conclusions: Findings build on earlier work by demonstrating that AWARE is effective in reducing alcohol use and related problems among emerging adults experiencing homelessness over a 2-year period. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose: For emerging adults in the United States, economic instability is a widespread problem with implications for the successful transition to adulthood. This study examines how two indicators of economic instability, homelessness and food insecurity, are associated with changes in health-related outcomes over a two-year period., Methods: The analytic sample (N = 2,182) completed online surveys in 2019-2020 (mean age 23 years) and 2021-2022 (mean age 25 years). Regression analyses were conducted for the full sample, as well as by sexual or gender diverse (SGD) identity (17.8% of sample identified as SGD) and race/ethnicity (76.3% identified as non-White)., Results: At age 23, 8.2% of participants reported homelessness and 31.2% reported food insecurity. In the full sample, homelessness and food insecurity were associated with increased depression, anxiety, physical ailments, and drug problems two years later. A similar pattern emerged for those identifying as non-SGD. The only associations for SGD-identifying participants were food insecurity with increased anxiety, depression, and physical ailments. Racial/ethnic differences indicated that homelessness was associated with increased depression and anxiety among Hispanics, and physical ailments and drug consequences among Asians, but fewer drug problems among Whites. Food insecurity was associated with increased depression in all racial/ethnic groups, anxiety among Hispanics and Asians, physical ailments among Whites and Asians, and drug problems among Asians., Discussion: Homelessness and food insecurity predicted worse health outcomes during the transition to adulthood, with varying results across SGD and racial/ethnic subgroups. It is important for future research to continue examining long-term effects of economic instability on health disparities during this important developmental period., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Young adults experiencing homelessness (YAEH) are at elevated risk for HIV compared to their stably housed peers. Preexposure prophylaxis (PrEP) is highly effective at preventing HIV infection, yet YAEH have been largely overlooked in PrEP efforts to date despite YAEH reporting high overall interest in PrEP. We assessed individual, social, and structural variables associated with PrEP interest and use among a sample of 195 YAEH (ages 18-25) recruited from drop-in centers across Los Angeles County who met criteria for HIV risk. In the current sample, though most had heard of PrEP (81.0%), the majority were not interested in taking PrEP (68.2%) and only a minority had used/were using PrEP (11.8%). YAEH who identified as sexual and/or gender minority, reported knowing someone who had used PrEP, or recently accessed sexual health services were more likely to have used and/or reported interest in using PrEP. Those who reported more episodes of heavy drinking were less likely to report having used PrEP. Suggestions are provided for better integrating PrEP-related services into existing behavioral and health service programs for YAEH, as well as leveraging peers and fostering positive social norms to reduce PrEP-related stigma and increase interest and use of PrEP among YAEH., (© 2023. The Author(s).)

As SARS-CoV-2 continues to circulate, antiviral treatments are needed to complement vaccines. The virus's main protease, 3CLPro, is an attractive drug target in part because it recognizes a unique cleavage site, which features a glutamine residue at the P1 position and is not utilized by human proteases. Herein, we report the invention of MK-7845, a novel reversible covalent 3CLPro inhibitor. While most covalent inhibitors of SARS-CoV-2 3CLPro reported to date contain an amide as a Gln mimic at P1, MK-7845 bears a difluorobutyl substituent at this position. SAR analysis and X-ray crystallographic studies indicate that this group interacts with His163, the same residue that forms a hydrogen bond with the amide substituents typically found at P1. In addition to promising in vivo efficacy and an acceptable projected human dose with unboosted pharmacokinetics, MK-7845 exhibits favorable properties for both solubility and absorption that may be attributable to the unusual difluorobutyl substituent.