H-NS is a bacterial transposon capture protein.

The histone-like nucleoid structuring (H-NS) protein is a DNA binding factor, found in gammaproteobacteria, with functional equivalents in diverse microbes. Universally, such proteins are understood to silence transcription of horizontally acquired genes. Here, we identify transposon capture as a major overlooked function of H-NS. Using genome-scale approaches, we show that H-NS bound regions are transposition "hotspots". Since H-NS often interacts with pathogenicity islands, such targeting creates clinically relevant phenotypic diversity. For example, in Acinetobacter baumannii, we identify altered motility, biofilm formation, and interactions with the human immune system. Transposon capture is mediated by the DNA bridging activity of H-NS and, if absent, more ubiquitous transposition results. Consequently, transcribed and essential genes are disrupted. Hence, H-NS directs transposition to favour evolutionary outcomes useful for the host cell.

Syringe services program staff and participant perspectives on changing drug consumption behaviors in response to xylazine adulteration.

BACKGROUND: Xylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence. METHODS: From June-July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes. RESULTS: From interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a "tranquilizer-like substance" that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers' experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation. CONCLUSIONS: Xylazine's emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.

Protective or potentially harmful? Altering drug consumption behaviors in response to xylazine adulteration.

Background: Xylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence. Methods: From June-July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes. Results: From interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a "tranquilizer-like substance" that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers' experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation. Conclusions: Xylazine's emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.

Specific microRNAs in stallion spermatozoa are potential biomarkers of high functionality.

Males of some species, from horses to humans, require medical help for subfertility problems. There is an urgent need for novel molecular assays that reflect spermatozoal function. In the last 25 years, studies examined RNAs in spermatozoa as a window into gene expression during their development and, more recently, for their functions in early embryo development. In clinics, more dense spermatozoa are isolated by density gradient centrifugation before use in artificial insemination to increase pregnancy rates. The objectives of the current study were to discover and quantify the microRNAs in stallion spermatozoa and identify those with differential expression levels in more dense versus less dense spermatozoa. First, spermatozoa from seven stallions were separated into more dense and less dense populations by density gradient centrifugation. Next, small RNAs were sequenced from each of the 14 RNA samples. We identified 287 different mature microRNAs within the 11,824,720 total mature miRNA reads from stallion spermatozoa. The most prevalent was miR-10a/b-5p. The less dense spermatozoa had fewer mature microRNAs and more microRNA precursor sequences than more dense spermatozoa, perhaps indicating that less dense spermatozoa are less mature. Two of the most prevalent microRNAs in more dense stallion spermatozoa were predicted to target mRNAs that encode proteins that accelerate mRNA decay. Nine microRNAs were more highly expressed in more dense spermatozoa. Three of those microRNAs were predicted to target mRNAs that encode proteins involved in protein decay. Both mRNA and protein decay are very active in late spermiogenesis but not in mature spermatozoa. The identified microRNAs may be part of the mechanism to shut down those processes. The microRNAs with greater expression in more dense spermatozoa may be useful biomarkers for spermatozoa with greater functional capabilities.

The Dependence of Online Gambling Businesses on High-Spending Customers: Quantification and Implications.

Online gambling has grown to be a significant industry but it faces regulatory threats because of perception that it is heavily dependent on a small segment of its customers who gamble heavily and at a level carrying elevated risk of harm. Employing a large multi-operator data set from Britain, which records individual transactions by some 140,000 individuals observed over one year, we are enabled to provide more precise estimates of the degree of concentration of revenue, compared with previous studies. High dependence on a relatively small number of customers is shown though there is variation from product to product in how small the group of account-holders of potential concern is. We conclude with a discussion of prospects for the industry in light of heightened awareness of gambling harm and resulting restrictions on online gambling spending introduced or proposed by governments or regulators in several jurisdictions.

Soluble Plasma Proteins of Tumor Necrosis Factor and Immunoglobulin Superfamilies Reveal New Insights into Immune Regulation in People with HIV and Opioid Use Disorder.

People with HIV (PWH) frequently suffer from Opioid (OP) Use Disorder (OUD). In an investigation of the impact of OUD on underlying immune dysfunction in PWH, we previously reported that OP use exacerbates inflammation in virally controlled PWH followed in the Infectious Diseases Elimination Act (IDEA) Syringe Services Program (SSP). Unexpectedly, Flu vaccination-induced antibody responses in groups with OUD were superior to PWH without OUD. Here, we investigated the profile of 48 plasma biomarkers comprised of TNF and Ig superfamily (SF) molecules known to impact interactions between T and B cells in 209 participants divided into four groups: (1) HIV+OP+, (2) HIV-OP+, (3) HIV+OP-, and (4) HIV-OP-. The differential expression of the top eight molecules ranked by median values in individual Groups 1-3 in comparison to Group 4 was highly significant. Both OP+ groups 1 and 2 had higher co-stimulatory TNF SF molecules, including 4-1BB, OX-40, CD40, CD30, and 4-1BBL, which were found to positively correlate with Flu Ab titers. In contrast, HIV+OP- exhibited a profile dominant in Ig SF molecules, including PDL-2, CTLA-4, and Perforin, with PDL-2 showing a negative correlation with Flu vaccine titers. These findings are relevant to vaccine development in the fields of HIV and OUD.

Case Series of Jamestown Canyon Virus Infections with Neurologic Outcomes, Canada, 2011-2016.

Jamestown Canyon virus (JCV) is a mosquitoborne orthobunyavirus in the California serogroup that circulates throughout Canada and the United States. Most JCV exposures result in asymptomatic infection or a mild febrile illness, but JCV can also cause neurologic diseases, such as meningitis and encephalitis. We describe a case series of confirmed JCV-mediated neuroinvasive disease among persons from the provinces of British Columbia, Alberta, Quebec, and Nova Scotia, Canada, during 2011-2016. We highlight the case definitions, epidemiology, unique features and clinical manifestations, disease seasonality, and outcomes for those cases. Two of the patients (from Quebec and Nova Scotia) might have acquired JCV infections during travel to the northeastern region of the United States. This case series collectively demonstrates JCV's wide distribution and indicates the need for increased awareness of JCV as the underlying cause of meningitis/meningoencephalitis during mosquito season.

PrEP for people who use opioids: A NIDA clinical trials network survey study in Southern U.S. cities where HIV incidence is high.

BACKGROUND: People who use opioids (PWUO) are at increased risk for HIV. Pre-exposure prophylaxis (PrEP) is effective but underutilized as HIV prevention among PWUO. This study examined predictors of willingness to take daily oral PrEP and long-acting injectable (LAI) PrEP among PWUO across eight Southern urban cities with high HIV incidence. METHODS: HIV-negative PWUO (N = 308) seeking services in community-based programs participated in this cross-sectional survey study. Measures included demographics, sexual risk behavior, substance use frequency, and awareness of and willingness to take oral and injectable PrEP. Data were analyzed using mixed-effects models. RESULTS: Willingness to take daily oral and LAI PrEP was moderately high (69.16% and 62.02%, respectively). Half had heard of PrEP, but only 4% had ever taken it. Only education and condomless vaginal sex predicted willingness to take oral PrEP. Only education predicted willingness to take LAI PrEP. Polysubstance use was prevalent, with substantial proportions of PWUO reporting frequent use of injection drugs (opioids or stimulants, 79.5%), non-injection opioids (73.3%), non-injection stimulants (71.1%), cannabis (62.6%), and hazardous drinking (29.6%). About 20% reported past-year condomless anal sex, and one-third reported past-year condomless vaginal sex. CONCLUSIONS: PWUO in this study were amenable to PrEP, particularly in light of education and condomless vaginal sex. Careful consideration for matching PrEP messaging to the PWUO audience is needed. PrEP promotion should expand beyond men who have sex with men to include groups such as these predominantly heterosexual, polysubstance-using PWUO with HIV risk who were open to both formulations of PrEP.

Project CHARIOT: study protocol for a hybrid type 1 effectiveness-implementation study of comprehensive tele-harm reduction for engagement of people who inject drugs in HIV prevention services.

BACKGROUND: People who inject drugs (PWID) remain a high priority population under the federal Ending the HIV Epidemic initiative with 11% of new HIV infections attributable to injection drug use. There is a critical need for innovative, efficacious, scalable, and community-driven models of healthcare in non-stigmatizing settings for PWID. We seek to test a Comprehensive-TeleHarm Reduction (C-THR) intervention for HIV prevention services delivered via a syringe services program (SSP). METHODS: The CHARIOT trial is a hybrid type I effectiveness-implementation study using a parallel two-arm randomized controlled trial design. Participants (i.e., PWID; n = 350) will be recruited from a syringe services program (SSP) in Miami, Florida. Participants will be randomized to receive either C-THR or non-SSP clinic referral and patient navigation. The objectives are: (1) to determine if the C-THR intervention increases engagement in HIV prevention (i.e., HIV pre-exposure prophylaxis; PrEP or medications for opioid use disorder; MOUD) compared to non-SSP clinic referral and patient navigation, (2) to examine the long-term effectiveness and cost-effectiveness of the C-THR intervention, and (3) to assess the barriers and facilitators to implementation and sustainment of the C-THR intervention. The co-primary outcomes are PrEP or MOUD engagement across follow-up at 3, 6, 9 and 12 months. For PrEP, engagement is confirmed by tenofovir on dried blood spot or cabotegravir injection within the previous 8 weeks. For MOUD, engagement is defined as screening positive for norbuprenorphine or methadone on urine drug screen; or naltrexone or buprenorphine injection within the previous 4 weeks. Secondary outcomes include PrEP adherence, engagement in HCV treatment and sustained virologic response, and treatment of sexually transmitted infections. The short and long term cost-effectiveness analyses and mixed-methods implementation evaluation will provide compelling data on the sustainability and possible impact of C-THR on comprehensive HIV prevention delivered via SSPs. DISCUSSION: The CHARIOT trial will be the first to our knowledge to test the efficacy of an innovative, peer-led telehealth intervention with PWID at risk for HIV delivered via an SSP. This innovative healthcare model seeks to transform the way PWID access care by bypassing the traditional healthcare system, reducing multi-level barriers to care, and meeting PWID where they are. TRIAL REGISTRATION: ClinicalTrials.gov NCT05897099. Trial registry name: Comprehensive HIV and Harm Prevention Via Telehealth (CHARIOT). Registration date: 06/12/2023.

Improving access to HIV care among people who inject drugs through tele-harm reduction: a qualitative analysis of perceived discrimination and stigma.

BACKGROUND: Tele-harm reduction (THR) is a telehealth-enhanced, peer-led, harm reduction intervention delivered within a trusted syringe services program (SSP) venue. The primary goal of THR is to facilitate linkage to care and rapid, enduring virologic suppression among people who inject drugs (PWID) with HIV. An SSP in Miami, Florida, developed THR to circumvent pervasive stigma within the traditional healthcare system. METHODS: During intervention development, we conducted in-depth interviews with PWID with HIV (n = 25) to identify barriers and facilitators to care via THR. We employed a general inductive approach to transcripts guided by iterative readings of the raw data to derive the concepts, themes, and interpretations of the THR intervention. RESULTS: Of the 25 PWID interviewed, 15 were in HIV care and adherent to medication; 4 were in HIV care but non-adherent; and 6 were not in care. Themes that emerged from the qualitative analysis included the trust and confidence PWID have with SSP clinicians as opposed to professionals within the traditional healthcare system. Several barriers to treatment were reported among PWID, including perceived and actual discrimination by friends and family, negative internalized behaviors, denial of HIV status, and fear of engaging in care. Facilitators to HIV care included empathy and respect by SSP staff, flexibility of telehealth location, and an overall destigmatizing approach. CONCLUSION: PWID identified barriers and facilitators to receipt of HIV care through the THR intervention. Interviews helped inform THR intervention development, centered on PWID in the destigmatizing environment of an SSP.

The environmentally-regulated interplay between local three-dimensional chromatin organisation and transcription of proVWX in E. coli.

Nucleoid associated proteins (NAPs) maintain the architecture of bacterial chromosomes and regulate gene expression. Thus, their role as transcription factors may involve three-dimensional chromosome re-organisation. While this model is supported by in vitro studies, direct in vivo evidence is lacking. Here, we use RT-qPCR and 3C-qPCR to study the transcriptional and architectural profiles of the H-NS (histone-like nucleoid structuring protein)-regulated, osmoresponsive proVWX operon of Escherichia coli at different osmolarities and provide in vivo evidence for transcription regulation by NAP-mediated chromosome re-modelling in bacteria. By consolidating our in vivo investigations with earlier in vitro and in silico studies that provide mechanistic details of how H-NS re-models DNA in response to osmolarity, we report that activation of proVWX in response to a hyperosmotic shock involves the destabilization of H-NS-mediated bridges anchored between the proVWX downstream and upstream regulatory elements (DRE and URE), and between the DRE and ygaY that lies immediately downstream of proVWX. The re-establishment of these bridges upon adaptation to hyperosmolarity represses the operon. Our results also reveal additional structural features associated with changes in proVWX transcript levels such as the decompaction of local chromatin upstream of the operon, highlighting that further complexity underlies the regulation of this model operon. H-NS and H-NS-like proteins are wide-spread amongst bacteria, suggesting that chromosome re-modelling may be a typical feature of transcriptional control in bacteria.

Evidence of a conserved mammalian immunosuppression mechanism in Lutzomyia longipalpis upon infection with Leishmania.

Introduction: Sand flies (Diptera: Phlebotominae) belonging to the Lutzomyia genus transmit Leishmania infantum parasites. To understand the complex interaction between the vector and the parasite, we have been investigating the sand fly immune responses during the Leishmania infection. Our previous studies showed that genes involved in the IMD, Toll, and Jak-STAT immunity pathways are regulated upon Leishmania and bacterial challenges. Nevertheless, the parasite can thrive in the vectors' gut, indicating the existence of mechanisms capable of modulating the vector defenses, as was already seen in mammalian Leishmania infections. Methods results and discussion: In this study, we investigated the expression of Lutzomyia longipalpis genes involved in regulating the Toll pathway under parasitic infection. Leishmania infantum infection upregulated the expression of two L. longipalpis genes coding for the putative repressors cactus and protein tyrosine phosphatase SHP. These findings suggest that the parasite can modulate the vectors' immune response. In mammalian infections, the Leishmania surface glycoprotein GP63 is one of the inducers of host immune depression, and one of the known effectors is SHP. In L. longipalpis we found a similar effect: a genetically modified strain of Leishmania amazonensis over-expressing the metalloprotease GP63 induced a higher expression of the sand fly SHP indicating that the L. longipalpis SHP and parasite GP63 increased expressions are connected. Immuno-stained microscopy of L. longipalpis LL5 embryonic cells cultured with Leishmania strains or parasite conditioned medium showed cells internalization of parasite GP63. A similar internalization of GP63 was observed in the sand fly gut tissue after feeding on parasites, parasite exosomes, or parasite conditioned medium, indicating that GP63 can travel through cells in vitro or in vivo. When the sand fly SHP gene was silenced by RNAi and females infected by L. infantum, parasite loads decreased in the early phase of infection as expected, although no significant differences were seen in late infections of the stomodeal valve. Conclusions: Our findings show the possible role of a pathway repressor involved in regulating the L. longipalpis immune response during Leishmania infections inside the insect. In addition, they point out a conserved immunosuppressive effect of GP63 between mammals and sand flies in the early stage of parasite infection.

Opioids exacerbate inflammation in people with well-controlled HIV.

Introduction: People with HIV (PWH) are known to have underlying inflammation and immune activation despite virologic control. Substance use including opioid dependence is common in this population and is associated with increased morbidity and reduced lifespan. The primary objective of the present study termed opioid immunity study (OPIS), was to investigate the impact of chronic opioids in PWH. Methods: The study recruited people with and without HIV who had opioid use disorder (OUD). Study participants (n=221) were categorized into four groups: HIV+OP+, n=34; HIV-OP+, n=66; HIV+OP-, n=55 and HIV-OP-, n=62 as controls. PWH were virally suppressed on ART and those with OUD were followed in a syringe exchange program with confirmation of OP use by urine drug screening. A composite cytokine score was developed for 20 plasma cytokines that are linked to inflammation. Cellular markers of immune activation (IA), exhaustion, and senescence were determined in CD4 and CD8 T cells. Regression models were constructed to examine the relationships of HIV status and opioid use, controlling for other confounding factors. Results: HIV+OP+ participants exhibited highest inflammatory cytokines and cellular IA, followed by HIV-OP+ for inflammation and HIV+OP- for IA. Inflammation was found to be driven more by opioid use than HIV positivity while IA was driven more by HIV than opioid use. In people with OUD, expression of CD38 on CD28-CD57+ senescent-like T cells was elevated and correlated positively with inflammation. Discussion: Given the association of inflammation with a multitude of adverse health outcomes, our findings merit further investigations to understand the mechanistic pathways involved.

Integrating Persons With Lived Experience in Opioid Use Disorder Education: A Small Group Exercise and Patient Panel.

OBJECTIVES: Based on increasing drug overdose deaths and a shortage of healthcare professionals trained in the management of opioid use disorder (OUD), it is imperative to improve health professional education in addiction medicine. This small group learning exercise and patient panel was designed to provide first year medical students with insights into the lives of people with OUD-through a lens of harm reduction-and to connect biomedical knowledge to the core values and professional themes of their doctoring courses. METHODS: Facilitators were assigned to each small group of 8 students for the harm reduction-centered Long and Winding Road small group case exercise. This was followed by a patient panel of 2 to 3 persons with OUD. The small group was conducted with first-year medical students as a virtual training session due to the COVID-19 pandemic. Students completed pre- and post-session surveys about agreement with statements pertaining to the learning objectives. RESULTS: The small group and patient panel were delivered over 8 sessions and attended by all first-year medical students (N = 201). Survey response rate was 67%. Post-session, there was significantly greater agreement with knowledge on all learning objectives compared to pre-session. Two relevant multiple-choice questions on the medical student final exam were answered correctly by 79% and 98% of students. CONCLUSION: Centering on people with lived experience, we completed small groups and patient panels to introduce concepts of OUD and harm reduction to first year medical students. Pre- and post-session surveys showed short-term achievement of the learning objectives.

An unexpected abundance of bidirectional promoters within Salmonella Typhimurium plasmids.

Transcription of the DNA template, to generate an RNA message, is the first step in gene expression. The process initiates at DNA sequences called promoters. Conventionally, promoters have been considered to drive transcription in a specific direction. However, in recent work, we showed that many prokaryotic promoters can drive divergent transcription. This is a consequence of key DNA sequences for transcription initiation being inherently symmetrical. Here, we used global transcription start site mapping to determine the prevalence of such bidirectional promoters in Salmonella Typhimurium. Surprisingly, bidirectional promoters occur three times more frequently in plasmid components of the genome compared to chromosomal DNA. Implications for the evolution of promoter sequences are discussed.

Project T-SHARP: study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs.

BACKGROUND: The resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue. METHODS: The T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n=240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA<200 copies/ml will be considered virally suppressed. The primary trial outcome is time-averaged HIV viral suppression (HIV RNA <200 copies/ml) over 3-, 6-, and 12-month follow-up. Secondary outcomes include initiation of MOUD measured by urine drug screen and HCV cure, defined as achieving 12-week sustained virologic response (negative HCV RNA at 12 weeks post treatment completion). A cost-effectiveness analysis will be performed. DISCUSSION: The T-SHARP Trial will be the first to our knowledge to test the efficacy of an innovative telehealth intervention with PWID with uncontrolled HIV delivered via an SSP to support HIV viral suppression. Tele-Harm Reduction is further facilitated by a peer to support adherence and bridge the digital divide. This innovative, flipped healthcare model sets aside the traditional healthcare system, reduces multi-level barriers to care, and meets PWID where they are. The T-SHARP trial is a pragmatic clinical trial that seeks to transform the way that PWID access HIV care and improve HIV clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05208697. Trial registry name: Tele-Harm Reduction. Registration date: January 26, 2022.

Implementation of an integrated infectious disease and substance use disorder team for injection drug use-associated infections: a qualitative study.

BACKGROUND: Hospitalizations for severe injection drug use-related infections (SIRIs) are characterized by high costs, frequent patient-directed discharge, and high readmission rates. Beyond the health system impacts, these admissions can be traumatizing to people who inject drugs (PWID), who often receive inadequate treatment for their substance use disorders (SUD). The Jackson SIRI team was developed as an integrated infectious disease/SUD treatment intervention for patients hospitalized at a public safety-net hospital in Miami, Florida in 2020. We conducted a qualitative study to identify patient- and clinician-level perceived implementation barriers and facilitators to the SIRI team intervention. METHODS: Participants were patients with history of SIRIs (n = 7) and healthcare clinicians (n = 8) at one implementing hospital (Jackson Memorial Hospital). Semi-structured qualitative interviews were performed with a guide created using the Consolidated Framework for Implementation Research (CFIR). Interviews were transcribed, double coded, and categorized by study team members using CFIR constructs. RESULTS: Implementation barriers to the SIRI team intervention identified by participants included: (1) complexity of the SIRI team intervention; (2) lack of resources for PWID experiencing homelessness, financial insecurity, and uninsured status; (3) clinician-level stigma and lack of knowledge around addiction and medications for opioid use disorder (OUD); and (4) concerns about underinvestment in the intervention. Implementation facilitators of the intervention included: (1) a non-judgmental, harm reduction-oriented approach; (2) the team's advocacy for PWID as a means of institutional culture change; (3) provision of close post-hospital follow-up that is often inaccessible for PWID; (4) strong communication with patients and their hospital physicians; and (5) addressing diverse needs such as housing, insurance, and psychological wellbeing. CONCLUSION: Integration of infectious disease and SUD treatment is a promising approach to managing patients with SIRIs. Implementation success depends on institutional buy-in, holistic care beyond the medical domain, and an ethos rooted in harm reduction across multilevel (inner and outer) implementation contexts.

The influence of schooling on performance in chess and at the Olympics.

At the macro-level, it is hard to test the hypothesis that increased schooling in a country will raise labour productivity but sectoral analyses may be tractable. In sports, output is homogenous in that countries' achievements are measurable in the same way. We examine country performances at the Chess Olympiad and the Olympic Games, contrasting tournaments where players in the first use only their minds but most in the second supply substantial physical effort or work with costly physical capital. Modelling success in either leads to a set of results familiar from sports literature: country performance depends on economic resources, represented by population size and per capita income. Supplementary variables capture over-performance by communist/ former communist countries. We then introduce a measure of average years of schooling. This significantly reduces the role of income, especially in chess. It also takes power away from the 'communist' variables, especially at the Olympics. These results suggest that much of any effect from income is mediated through schooling: investment in education is associated with elevated productivity. Increased productivity is observed in both settings, one a knowledge-intensive sub-sector and the other dependent to a significant extent on either raw physical strength or expensive capital input. Supplementary Information: The online version contains supplementary material available at 10.1007/s00181-022-02259-9.

"We want everything in a one-stop shop": acceptability and feasibility of PrEP and buprenorphine implementation with mobile syringe services for Black people who inject drugs.

INTRODUCTION: A recent surge in HIV outbreaks, driven by the opioid and stimulant use crises, has destabilized our progress toward targets set forth by Ending the HIV Epidemic: A Plan for America for the high-priority community of people who inject drugs (PWID), particularly Black PWID. METHODS: In order to ascertain the acceptability and feasibility of using a mobile syringe services program (SSP) for comprehensive HIV prevention via PrEP and medications for opioid use disorder (MOUD), our mixed methods approach included a quantitative assessment and semi-structured qualitative interviews with Black PWID (n = 30) in Miami-Dade County who were actively engaged in mobile syringe services. RESULTS: Participants felt that delivery of MOUD and PrEP at a mobile SSP would be both feasible and acceptable, helping to address transportation, cost, and stigma barriers common within traditional healthcare settings. Participants preferred staff who are compassionate and nonjudgmental and have lived experience. CONCLUSIONS: A mobile harm reduction setting could be an effective venue for delivering comprehensive HIV prevention services to Black PWID, a community that experiences significant barriers to care via marginalization and racism in a fragmented healthcare system.

Opioid Use Disorder Curriculum: Medicine Clerkship Standardized Patient Case, Small-Group Activity, and Patient Panel.

Introduction: The overdose crisis remains a critical public health problem, creating an urgent need to train physicians in the treatment and management of opioid use disorder (OUD). Our medicine clerkship module aimed to close this gap by training and assessing students' motivational interviewing skills, harm reduction knowledge, and use of nonstigmatizing language in the treatment of patients with OUD. Methods: We evaluated the impact of a small-group, case-based activity and patient panel on the clinical documentation skills of students in a medicine clerkship. Clinical documentation was based on an observed structured clinical examination of a standardized patient with OUD and was evaluated using a grading rubric that followed the module learning objectives. Students also submitted reflections on the curriculum. Results: Qualitative responses (n = 40) from students evaluating the small-group activity and patient panel exercise revealed overall student satisfaction with the patient panel and exposure to patients living with OUD. Three themes emerged from student reflections: (1) humanity, (2) different paths to recovery, and (3) using nonstigmatizing language. For the quantitative test, students' (n = 39) mean clinical documentation scores before and after the small-group activity and patient panel increased from 10.1 to 11.3 out of 13.5 possible points. There was a significant difference between mean pretest and posttest scores (p < .001). Discussion: The medicine clerkship provided an acceptable and feasible opportunity for implementing a multifaceted educational experience for students with significant immediate impact on their evaluation of patients with OUD.