Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.

The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC50 ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC50 ranging from 1.2 to 2.3 µM. These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools such as molecular docking and quantitative structure-activity relationship (QSAR) models to analyze protein-ligand interactions, revealing that these naphthoquinones exhibit a protein binding pattern similar to brequinar, a potent HsDHODH inhibitor. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.

Electrostimulable polymeric films with hyaluronic acid and lipid nanoparticles for simultaneous topical delivery of macromolecules and lipophilic drugs.

This study focused on developing electrically stimulable hyaluronic acid (HA) films incorporating lipid nanoparticles (NPs) designed for the topical administration of lipophilic drugs and macromolecules. Based on beeswax and medium-chain triglycerides, NPs were successfully integrated into silk fibroin/chitosan films containing HA (NP-HA films) at a density of approximately 1011 NP/cm2, ensuring a uniform distribution. This integration resulted in a 40% increase in film roughness, a twofold decrease in Young's modulus, and enhanced film flexibility and bioadhesion work. The NP-HA films, featuring Ag/AgCl electrodes, demonstrated the capability to conduct a constant electrical current of 0.2 mA/cm2 without inducing toxicity in keratinocytes and fibroblasts during a 15-min application. Moreover, the NPs facilitated the homogeneous distribution of lipophilic drugs within the film, effectively transporting them to the skin and uniformly distributing them in the stratum corneum upon film administration. The sustained release of HA from the films, following Higuchi kinetics, did not alter the macroscopic characteristics of the film. Although anodic iontophoresis did not noticeably affect the release of HA, it did enhance its penetration into the skin. This enhancement facilitated the permeation of HA with a molecular weight (MW) of up to 2 × 105 through intercellular and transcellular routes. Confocal Raman spectroscopy provided evidence of an approximate 100% increase in the presence of HA with a MW in the range of 1.5-1.8 × 106 in the viable epidermis of human skin after only 15 min of iontophoresis applied to the films. Combining iontophoresis with NP-HA films exhibits substantial potential for noninvasive treatments focused on skin rejuvenation and wound healing.

Access challenges to opioid use disorder treatment among individuals experiencing homelessness: Voices from the streets.

BACKGROUND: Achieving equitable access to medications for opioid use disorder (MOUD) such as buprenorphine is a pressing issue. Evidence suggests disparities in MOUD access based on race and socioeconomic status, further exacerbated by the COVID-19 pandemic. However, the drivers behind this access gap remain poorly understood. This study explores barriers to treatment access among individuals with opioid use disorder (OUD) experiencing homelessness. METHODS: We interviewed 28 individuals in and around the Boston Public Health Commission (BPHC) Engagement Center, an area known for its high density of active substance use and homelessness. We asked about people's experiences, perceptions, and attitudes toward OUD treatment. We conducted a thematic analysis of our interview data. RESULTS: Fifty-four percent of participants sampled were not prescribed MOUD. None of the participants reported having an active prescription of sublingual buprenorphine or buprenorphine/naloxone. White participants were more likely to have been prescribed buprenorphine in the past compared to participants of other races even in this socioeconomically homogeneous sample. Themes that emerged in our data included challenges to accessing MOUD due to reduced services during the COVID-19 pandemic, lost or stolen medications, fewer inpatient withdrawal management beds for women, transportation challenges, fear of adverse effects of MOUD, the perception that taking MOUD replaces one addiction for another, and community disapproval of MOUD. Participants also reported stigma and discrimination based on race, gender, and socioeconomic status. CONCLUSION: Systems and individual-level factors contribute to the MOUD treatment gap across race and socioeconomic status. The COVID-19 pandemic posed additional access challenges. This study provides important, actionable insights about the barriers faced by a particularly vulnerable population of individuals with OUD experiencing homelessness.

A Peer Recovery Coach Intervention for Hospitalized Patients with Opioid Use Disorder: A Pilot Randomized Controlled Trial.

OBJECTIVES: Patients with opioid use disorder (OUD) are increasingly being hospitalized for acute medical illnesses. Despite initiation of medications for OUD (MOUDs), many discontinue treatment after discharge. To evaluate whether a psychosocial intervention can improve MOUD retention after hospitalization, we conducted a pilot randomized controlled trial of a peer recovery coach intervention. METHODS: An existing peer recovery coach intervention was adapted for this trial. Hospitalized adults with OUD receiving MOUD treatment were randomized to receive either a recovery coach intervention or treatment-as-usual. For those in the intervention arm, the coach guided the participant to complete a relapse prevention plan, maintained contact throughout the 6-month follow-up period, encouraged MOUD continuation, and helped to identify community resources. Those receiving treatment-as-usual were discharged with a referral to outpatient treatment. Primary outcome was retention in MOUD treatment at 6 months. Secondary outcomes were the proportion of participants readmitted to the hospital and the number of days until treatment discontinuation and to hospital readmission. RESULTS: Twenty-five individuals who provided consent and randomized to the recovery coach intervention (n = 13) or treatment-as-usual (n = 12) were included in the analysis. No significant differences were found in the proportion of participants retained in MOUD treatment at 6 months (38.5% vs 41.7%, P = 0.87), proportion of participants readmitted at 6 months (46.2% vs 41.2%, P = 0.82), or the time to treatment discontinuation (log-rank P = 0.92) or readmission (log-rank P = 0.85). CONCLUSIONS: This pilot trial failed to demonstrate that a recovery coach intervention improved MOUD treatment retention compared with treatment-as-usual among hospitalized individuals with OUD.

Enolase represents a metabolic checkpoint controlling the differential exhaustion programmes of hepatitis virus-specific CD8+ T cells.

OBJECTIVE: Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction. DESIGN: Metabolic state, exhaustion and transcriptome of virus-specific CD8+ T cells from chronic HBV-infected (n=31) and HCV-infected patients (n=52) were determined ex vivo and during direct-acting antiviral (DAA) therapy. Metabolic flux and metabolic checkpoints were tested in vitro. Intrahepatic virus-specific CD8+ T cells were analysed by scRNA-Seq in a HBV-replicating murine in vivo model of acute and chronic infection. RESULTS: HBV-specific (core18-27, polymerase455-463) and HCV-specific (NS31073-1081, NS31406-1415, NS5B2594-2602) CD8+ T cell responses exhibit heterogeneous metabolic profiles connected to their exhaustion states. The metabolic state was connected to the exhaustion profile rather than the aetiology of infection. Mitochondrial impairment despite intact glucose uptake was prominent in severely exhausted T cells linked to elevated liver inflammation in chronic HCV infection and in HBV polymerase455-463 -specific CD8+ T cell responses. In contrast, relative metabolic fitness was observed in HBeAg-negative HBV infection in HBV core18-27-specific responses. DAA therapy partially improved mitochondrial programmes in severely exhausted HCV-specific T cells and enriched metabolically fit precursors. We identified enolase as a metabolic checkpoint in exhausted T cells. Metabolic bypassing improved glycolysis and T cell effector function. Similarly, enolase deficiency was observed in intrahepatic HBV-specific CD8+ T cells in a murine model of chronic infection. CONCLUSION: Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies.

Attitudes Regarding Medications for Opioid Use Disorder Among Peer Recovery Coaches.

OBJECTIVES: A growing number of individuals are employed as peer recovery coaches to mentor, support, and educate those in recovery. Despite the robust evidence base for the benefits of medications for treating opioid use disorder (OUD), prior research has identified peers in recovery to hold both positive and negative attitudes toward medications for OUD (MOUDs). We aimed to survey peer recovery coaches in Massachusetts about their attitudes toward working with individuals utilizing MOUDs. METHODS: All 202 individuals certified as peer recovery coaches in Massachusetts were invited to participate in a brief, anonymous online survey between August and October 2020. The survey collected the respondents' age, sex, certification year, duration of employment as a coach, personal history of substance use disorders, and MOUD treatment. RESULTS: A total of 129 responses were received, representing a 63.9% response rate. Eighty-six (64.3%) reported a personal history of OUD, of whom 64 (74.4%) reported prior MOUD treatment. The majority held positive views about MOUDs, endorsing them as appropriate treatments to achieve sobriety. Coaches with personal history of MOUDs were more likely to report enjoying working with patients on methadone. Coaches without any personal history of OUD or MOUDs were older, more likely to have an alcohol use disorder, and more likely to encourage drug-free treatments before MOUDs and shorter duration of MOUD treatment. CONCLUSIONS: Results indicate that peer recovery coaches in Massachusetts hold generally positive attitudes toward MOUDs, but those without any personal history of OUD or MOUDs may be less likely to encourage MOUD treatment.

Cannabidiol Effect on Cue-Induced Craving for Individuals with Opioid Use Disorder Treated with Buprenorphine: A Small Proof-of-Concept Open-Label Study.

Background: Opioid use disorder (OUD) remains a major public health concern. Despite the use of medications for OUD such as buprenorphine, the current gold-standard treatment, relapse in the context of increased craving remains common. Cannabidiol (CBD) has been shown to reduce cue-induced craving in individuals with OUD, but among those who were not receiving any buprenorphine treatment. This small proof-of-concept open-label study sought to evaluate the effect of CBD on cue-induced craving among individuals with OUD who were being actively treated with buprenorphine. Methods: Participants (n = 5) received CBD (Epidiolex®) 600 mg once daily for 3 consecutive days in an open-label manner. Primary outcome was cue-induced craving measured on a visual analog scale of 0 to 10, calculated as the difference in craving in response to drug-related versus neutral cues. The cue-reactivity paradigm was performed at baseline before CBD administration, and was repeated after 3 days of CBD. Secondary outcomes included scores on depression, anxiety, pain, opioid withdrawal, and side effects. Results: All participants were actively taking buprenorphine for an average of 37.8 months (range 1-120 months). Cue-induced craving was significantly lower after CBD dosing compared with baseline (0.4 vs. 3.2, paired t-test, p = 0.0046). No significant changes in scores for depression, anxiety, pain, or opioid withdrawal were noted. CBD was well tolerated, although one participant experienced moderate sedation; otherwise, no other adverse effects were reported. Conclusions: Given the high risk for bias in a small uncontrolled open label study such as this, results must be interpreted with caution. A larger adequately powered trial with a suitable control group is needed to confirm the finding that CBD may help to reduce cue-induced craving among individuals with OUD currently on buprenorphine treatment. Research should further evaluate whether adjunctive use of CBD can improve clinical outcomes for individuals with OUD maintained on buprenorphine. ClinicalTrials.gov (NCT04192370).

Implementation of the 'PicNic' handover huddle: A quality improvement project to improve the transition of infants between paediatric and neonatal intensive care units.

AIMS: Thorough handover and effective communication are crucial to the transfer of clinical information between different intensive care units. Following a sentinel patient safety event, an improvement project was initiated to reduce patient safety risks associated with the transfer of complex patients between the neonatal and paediatric intensive care. METHODS: A handover tool was implemented over a 4-month period, guiding handover through means of a handover huddle. The tool ensured a full ISBAR (Introduction, Situation, Background, Assessment, Response) handover, with a specified attendance register. It acknowledged specific safety points inclusive of outstanding investigations, procedural history and medication transcription. Post implementation, huddle checklist sheets were audited for compliance and a staff satisfaction survey was conducted. RESULTS: Thirty-nine handovers took place during this trial period, of which 69% were captured in the huddle process. Senior medical and nursing staff attendance was greater than 95% throughout the process, and 100% of huddles attended to a full ISBAR handover. Sixty staff satisfaction survey responses were received, 90% of which identified the process to improve the safety of patient handover. Responses also identified safety issues such as discontinuity of medication transcription between the units, and inappropriate patient transfers occurring outside of working hours. Qualitative feedback highlighted how the tool improved interdepartmental educational and collaboration opportunities. CONCLUSIONS: The 'PicNic' huddle effectively facilitated a standardised handover between paediatric and neonatal intensive care. It also recognised the importance of interdepartmental collaboration and education surrounding culturally different clinical practices. Further improvement cycles continue to progress the tool and initiate a digital format for ongoing use.

Healing journeys: experiences of young Aboriginal people in an urban Australian therapeutic community drug and alcohol program.

Disproportionately high numbers of Aboriginal young people access residential alcohol and other drug programs in Australia. While demand is high, these programs often have low numbers of Aboriginal staff. Residential programs, however, generally offer supports that reflect features of Aboriginal health care - holistic, group-based, connected to local communities, and addressing determinants of health. The qualitative research outlined in this paper was a collaboration between a mainstream residential therapeutic community program and two Aboriginal community-controlled organisations, and Aboriginal young people and researchers, with Aboriginal research leadership. It used an Aboriginal healing framework to understand the experiences of 12 young Aboriginal people in the program, triangulated with 19 key informant interviews. This provided an opportunity to understand how Indigenous knowledge about healing related to mainstream programs and the experiences of Aboriginal young people. This moves beyond individualist and deficit-focused conceptions of youth alcohol and drug use and centres Aboriginal cultures as healing. Findings point to the need for critically self-reflective mainstream organisations, a larger Aboriginal workforce with leadership roles, partnerships with Aboriginal Elders and organisations, and an investment in Aboriginal community-controlled alcohol and other drug services.

Smartphone Ownership, Smartphone Utilization, and Interest in Using Mental Health Apps to Address Substance Use Disorders: Literature Review and Cross-sectional Survey Study Across Two Sites.

BACKGROUND: In recent years, there has been increasing interest in implementing digital technologies to diagnose, monitor, and intervene in substance use disorders. Smartphones are now a vehicle for facilitating telepsychiatry visits, measuring health metrics, and communicating with health care professionals. In light of the COVID-19 pandemic and the movement toward web-based and hybrid clinic visits and meetings, it has become especially salient to assess phone ownership among individuals with substance use disorders and their comfort in navigating phone functionality and using phones for mental health purposes. OBJECTIVE: The aims of this study were to summarize the current literature around smartphone ownership, smartphone utilization, and the acceptability of using smartphones for mental health purposes and assess these variables across two disparate substance use treatment sites. METHODS: We performed a focused literature review via a search of two academic databases (PubMed and Google Scholar) for publications since 2007 on the topics of smartphone ownership, smartphone utilization, and the acceptability of using mobile apps for mental health purposes among the substance use population. Additionally, we conducted a cross-sectional survey study that included 51 participants across two sites in New England-an inpatient detoxification unit that predominantly treats patients with alcohol use disorder and an outpatient methadone maintenance treatment clinic. RESULTS: Prior studies indicated that mobile phone ownership among the substance use population between 2013 and 2019 ranged from 83% to 94%, while smartphone ownership ranged from 57% to 94%. The results from our study across the two sites indicated 96% (49/51) mobile phone ownership and 92% (47/51) smartphone ownership among the substance use population. Although most (43/49, 88%) patients across both sites reported currently using apps on their phone, a minority (19/48, 40%) reported previously using any apps for mental health purposes. More than half of the participants reported feeling at least neutrally comfortable with a mental health app gathering information regarding appointment reminders (32/48, 67%), medication reminders (33/48, 69%), and symptom surveys (26/45, 58%). Most patients were concerned about privacy (34/51, 67%) and felt uncomfortable with an app gathering location (29/47, 62%) and social (27/47, 57%) information for health care purposes. CONCLUSIONS: The majority of respondents reported owning a mobile phone (49/51, 96%) and smartphone (47/51, 92%), consistent with prior studies. Many respondents felt comfortable with mental health apps gathering most forms of personal information and with communicating with their clinician about their mental health. The differential results from the two sites, namely greater concerns about the cost of mental health apps among the methadone maintenance treatment cohort and less experience with downloading apps among the older inpatient detoxification cohort, may indicate that clinicians should tailor technological interventions based on local demographics and practice sites and that there is likely not a one-size-fits-all digital psychiatry solution.

A New Approach to Atopic Dermatitis Control with Low-Concentration Propolis-Loaded Cold Cream.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is difficult to treat. Traditional cold cream, a water-in-oil emulsion made from beeswax, is used to alleviate AD symptoms in clinical practice, although its effectiveness has not been scientifically proven. The addition of propolis has the potential to impart anti-inflammatory properties to cold cream. However, in high concentrations, propolis can trigger allergic reactions. Thus, the objective of this work was to develop a cold cream formulation based on purified beeswax containing the same amount of green propolis present in raw beeswax. The impact of adding this low propolis concentration to cold cream on AD control was evaluated in patients compared to cold cream without added propolis (CBlank). Raw beeswax was chemically characterized to define the propolis concentration added to the propolis-loaded cold cream (CPropolis). The creams were characterized as to their physicochemical, mechanical, and rheological characteristics. The effect of CPropolis and CBlank on the quality of life, disease severity, and skin hydration of patients with AD was evaluated in a triple-blind randomized preclinical study. Concentrations of 34 to 120 ng/mL of green propolis extract reduced TNF-α levels in LPS-stimulated macrophage culture. The addition of propolis to cold cream did not change the cream's rheological, mechanical, or bioadhesive properties. The preclinical study suggested that both creams improved the patient's quality of life. Furthermore, the use of CPropolis decreased the disease severity compared to CBlank.

Family factors and health-related quality of life within 6 months of completion of childhood cancer treatment.

OBJECTIVE: The transition from active cancer treatment to survivorship represents a period of uncertainty for youth and their families, but factors associated with adaptation during this period are understudied. We evaluated associations among cancer and treatment-related variables, family factors (family functioning, caregiver health-related quality of life [HRQL], and caregiver distress), and patient HRQL after treatment completion. We assessed the indirect effects of neurocognitive difficulties on youth HRQL through family factors. METHODS: One hundred fifty-four caregivers (of patients' ages 0-18 years) and 52 youth (ages 7-18 years) completed questionnaires assessing family factors, neurocognitive difficulties, and HRQL for patients within 6 months following treatment completion. Electronic health records were reviewed for cancer and treatment-related information. Bootstrapping analyses assessed whether neurocognitive function had indirect effects on HRQL through family factors. RESULTS: Family factors were associated with self- and caregiver reports of children's HRQL. Controlling for demographic, cancer, and treatment covariates, caregiver reports of their child's neurocognitive difficulties had an indirect effect on their reports of child physical HRQL through family functioning. Caregiver reports of their child's neurocognitive difficulties indirectly related to caregiver reports of child psychosocial HRQL through family functioning and caregiver HRQL. Indirect effects for self-reported neurocognitive difficulties and HRQL were not supported. CONCLUSIONS: Findings highlight the need for routine psychosocial screening for youth and caregiver reports of family adjustment and HRQL during the transition off treatment. Providers are encouraged to offer interventions matched to specific needs for families at risk for poor family functioning to improve patient outcomes as they transition off treatment.

"Pain is Subjective": A Mixed-Methods Study of Provider Attitudes and Practices Regarding Pain Management in Sickle Cell Disease Across Three Countries.

CONTEXT: Sickle cell disease (SCD), an autosomal recessive blood disorder, affects millions of people worldwide. Approximately 80% of all cases are located in Africa. OBJECTIVES: This cross-national, interdisciplinary, collaborative study investigated provider attitudes about, and practices for, managing (assessing and treating) SCD pain. METHODS: We conducted 111 quantitative surveys and 52 semistructured interviews with health-care providers caring for adults and/or children with SCD in Cameroon, Jamaica, and the U.S. RESULTS: Applying Haywood's scale for assessing SCD provider attitudes, the Jamaica site scored lower on "Negative Attitudes" than the Cameroonian and U.S. sites (P = 0.03 and <0.001, respectively). Providers at the U.S. site scored lower on "Positive Attitudes" than other sites (P < 0.001). "Red Flag" scores at the Cameroon sites were lower than at other sites (P < 0.001). Qualitative results across all three sites describe the current practices for SCD pain management, as well as the challenges surrounding management for health providers, including pain subjectivity, patient-provider and parent-provider relationships, resource availability, perceptions of drug-seeking behavior, and adherence. Providers also spontaneously offered solutions to reported challenges. CONCLUSION: Overall, findings reveal that SCD provider attitudes toward their patients differed across sites, yet at all three sites, treating SCD pain is multidimensional.

Feasibility and Safety of Outpatient Parenteral Antimicrobial Therapy in Conjunction With Addiction Treatment for People Who Inject Drugs.

BACKGROUND: Research is limited on combining outpatient parenteral antimicrobial therapy (OPAT) with addiction treatment for people who inject drugs (PWID) with serious infections. METHODS: This is a retrospective study of PWID (n = 68) requiring intravenous antibiotics evaluated for suitability for our OPAT program with concurrent addiction treatment. RESULTS: Most common infections were bacteremia and/or endocarditis (73.5%), bone and/or joint infections (32.4%), and epidural abscess (22.1%). Of the 20 patients (29.4%) who qualified, 100.0% completed the course of antibiotics, 30.0% experienced a 30-day readmission, and 15.0% relapsed. No overdoses, deaths, or peripherally inserted central catheter-line complications were reported. CONCLUSIONS: Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections.

Impact of Medications for Opioid Use Disorder on Discharge Against Medical Advice Among People Who Inject Drugs Hospitalized for Infective Endocarditis.

BACKGROUND AND OBJECTIVES: The impact of medications for opioid use disorder (MOUD) on against medical advice (AMA) discharges among people who inject drugs (PWID) hospitalized for endocarditis is unknown. METHODS: A retrospective review of all PWID hospitalized for endocarditis at our institution between 2016 and 2018 (n = 84). RESULTS: PWID engaged with MOUD at admission, compared with those who were not, were less likely to be discharged AMA but this did not reach statistical significance in adjusted analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.033-1.41; P = .11). Among out-of-treatment individuals, newly initiating MOUD did not lead to significantly fewer AMA discharges (OR, 0.98; 95% CI, 0.26-3.7; P = .98). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: PWID hospitalized for endocarditis are at high risk for discharge AMA but more research is needed to understand the impact of MOUD. (Am J Addict 2020;29:155-159).

Using Natural Language Processing and Machine Learning to Identify Hospitalized Patients with Opioid Use Disorder.

Opioid use disorder (OUD) represents a global public health crisis that challenges classic clinical decision making. As existing hospital screening methods are resource-intensive, patients with OUD are significantly under-detected. An automated and accurate approach is needed to improve OUD identification so that appropriate care can be provided to these patients in a timely fashion. In this study, we used a large-scale clinical database from Mass General Brigham (MGB; formerly Partners HealthCare) to develop an OUD patient identification algorithm, using multiple machine learning methods. Working closely with an addiction psychiatrist, we developed a set of hand-crafted rules for identifying information suggestive of OUD from free-text clinical notes. We implemented a natural language processing (NLP)-based classification algorithm within the Medical Text Extraction, Reasoning and Mapping System (MTERMS) tool suite to automatically label patients as positive or negative for OUD based on these rules. We further used the NLP output as features to build multiple machine learning and a neural classifier. Our methods yielded robust performance for classifying hospitalized patients as positive or negative for OUD, with the best performing feature set and model combination achieving an F1 score of 0.97. These results show promise for the future development of a real-time tool for quickly and accurately identifying patients with OUD in the hospital setting.

Sexual Orientation, Religious Coping, and Drug Use in a Sample of HIV-Infected African-American Men Living in the Southern USA.

Religiosity and spirituality are associated with reduced drug use in the general population, but it is unclear whether this relationship generalizes to sexual minorities. This study investigated the relationship between religious coping, drug use, and sexual orientation in a sample of HIV-infected African-American men (40 heterosexuals; 64 sexual minorities). Most participants (76%) reported being "moderately" or "very" religious. We found no main effect of religious coping or sexual orientation on frequency of drug use. However, there was an interaction between positive religious coping and sexual orientation. Among heterosexuals, positive religious coping was inversely associated with frequency of drug use. However, this relationship was not significant among sexual minorities. Findings suggest HIV-infected African-American sexual minorities living in the South may need additional coping resources to decrease vulnerability to drug use.

A Comparison of Motivations for Marijuana Use in HIV-Positive and HIV-Negative Adults.

While medicinal marijuana use is common among persons with HIV, it is not known whether persons with HIV are more motivated to use marijuana medically compared to HIV-negative counterparts. This study examined motivations for marijuana use in a sample of 94 HIV+ and HIV- adults. Participants used marijuana 21.27 days in the last 30 days on average. HIV+ participants reported using marijuana for medical reasons more often than HIV- participants, but HIV+ and HIV- participants did not differ in other domains. Problematic marijuana use was associated with motives, regardless of HIV status. Motives were associated with mental and physical health functioning, but there were no interactions between motivations and HIV status. Overall this study found that motivations were similar for HIV+ and HIV- participants. Future research including qualitative work to further understand motivations would benefit the field, as would research examining the effectiveness of marijuana in treating physical symptoms.

Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.

Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, and heterogeneity remains largely unknown, hampering their clinical use. High-dimensional techniques were used to elucidate transcriptional, phenotypic, and functional differences between human in vivo and in vitro generated mononuclear phagocytes to facilitate their full potential in the clinic. We demonstrate that monocytes differentiated by macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) resembled in vivo inflammatory macrophages, while moDCs resembled in vivo inflammatory DCs. Moreover, differentiated monocytes presented with profound transcriptomic, phenotypic, and functional differences. Monocytes integrated GM-CSF and IL-4 stimulation combinatorically and temporally, resulting in a mode- and time-dependent differentiation relying on NCOR2. Finally, moDCs are phenotypically heterogeneous and therefore necessitate the use of high-dimensional phenotyping to open new possibilities for better clinical tailoring of these cellular therapies.