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The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use disorder (OUD) at 6 months post-release. Three randomized trials (combined N = 330) were combined to assess whether MOUD (extended-release naltrexone or interim methadone) initiated prior to release from jail with or without PN would reduce the likelihood of a DSM-5 diagnosis of OUD 6 months post-release relative to enhanced treatment-as-usual (ETAU). Across the three studies, assignment to MOUD compared to ETAU was not associated with an OUD diagnosis at 6 months post-release (69% vs. 75%, respectively, OR = 0.67, 95% CI: 0.42 to 1.20). Similarly, PN compared to MOUD without PN was not associated with an OUD diagnosis (63% vs 77%, respectively, OR = 0.61, 95% CI: 0.27 to 1.53). Results underscore the need to further optimize the effectiveness of MOUD for patients initiating treatment in jail, beginning with an emphasis on post-release treatment adherence.

Background The advent of low cost, high throughput DNA sequencing has led to the availability of thousands of complete genome sequences for a wide variety of bacterial species. Examining and interpreting genetic variation on this scale represents a significant challenge to existing methods of data analysis and visualisation. Results Starting with the output of standard pangenome analysis tools, we describe the generation and analysis of interactive, 3D network graphs to explore the structure of bacterial populations, the distribution of genes across a population, and the syntenic order in which those genes occur, in the new open-source network analysis platform, Graphia. Both the analysis and the visualisation are scalable to datasets of thousands of genome sequences. Conclusions We anticipate that the approaches presented here will be of great utility to the microbial research community, allowing faster, more intuitive, and flexible interaction with pangenome datasets, thereby enhancing interpretation of these complex data.

Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone. To properly chaperone its clientele, Hsp90 proceeds through an ATP-dependent conformational cycle influenced by posttranslational modifications (PTMs) and assisted by a number of co-chaperone proteins. Although Hsp90 conformational changes in solution have been well-studied, regulation of these complex dynamics in cells remains unclear. Phosphorylation of human Hsp90α at the highly conserved tyrosine 627 has previously been reported to reduce client interaction and Aha1 binding. Here we report that these effects are due to a long-range conformational impact inhibiting Hsp90α N-domain dimerization and involving a region of the middle domain/carboxy-terminal domain interface previously suggested to be a substrate binding site. Although Y627 is not phosphorylated in yeast, we demonstrate that the non-conserved yeast co-chaperone, Hch1, similarly affects yeast Hsp90 (Hsp82) conformation and function, raising the possibility that appearance of this PTM in higher eukaryotes represents an evolutionary substitution for HCH1 . The eukaryotic heat shock protein 90 (Hsp90) undergoes an ATP-dependent conformational cycle that is influenced by posttranslational modifications and co-chaperones. Here, the authors show that the yeast co-chaperone Hch1 can be functionally substituted by site-specific phosphorylation in human Hsp90.

Deconstruction—the systematic disassembly of reusable and recyclable components and materials—is being actively promoted in a growing number of US cities to reduce the enormous amount of construction demolition waste sent to landfill. Research has highlighted local and regionally specific criteria influencing the decision on deconstruction, but it remains unclear how to decide which city-owned condemned properties in Pittsburgh should be considered for the new deconstruction pilot program. Therefore, this study establishes a prioritization model to distinguish the relative importance of factors using the analytic hierarchy process (AHP). According to local experts, the four most impactful criteria are the environmental impact, economic impact, resources and type of properties. Fourteen factors within these criteria are selected for detailed comparison. The relative importance of these factors is then used to weight spatial map overlays to classify condemned properties into four deconstruction value categories. As a result, this study offers a new methodology to evaluate potential deconstruction projects by weighting the criteria most valued by decision-makers in Pittsburgh, which could be altered and expanded to fit the values of other cities.Practice relevanceA robust decision-making process involving experts, local stakeholders and city officials is created for the selection of buildings to be deconstructed rather than demolished. The decision process is based on a comprehensive analysis of environmental, economic, resource and building-type criteria. A clear process is also established for the identification of the advantages and limitations of the approach. This provides a prioritization of potential deconstruction locations based on experts’ subjective judgements and an objective dataset, concluding that the highest value of deconstruction should be first considered by decision-makers. This pilot project provides a proof of concept of the group decision-making process. City-owned condemned buildings in Pittsburgh were divided into four categories with different deconstruction values by the combination of AHP and geographic information systems (GIS) analysis. The relationship and consistency between the condemned properties in each category and the deconstruction value are considered in detail.

Background Few studies have documented patient attitudes and experiences with extended-release naltrexone (XR-NTX) opioid relapse prevention in criminal justice settings. This study assessed barriers and facilitators of jail-to-community reentry among adults with opioid use disorder (OUD) treated with XR-NTX, buprenorphine, methadone, and no medications. Methods This qualitative study conducted individual interviews with a purposeful and convenience sample of adults with OUD who were recently released from NYC jails. XR-NTX, no medication, and methadone participants were concurrently enrolled in a large randomized controlled trial evaluating XR-NTX vs. a no medication Enhanced Treatment As Usual (ETAU) condition, or enrolled in a non-randomized quasi-experimental methadone maintenance cohort. Buprenorphine participants were referred from NYC jails to a public hospital office-based buprenorphine program and not enrolled in the parent trial. Interviews were audio recorded, transcribed, independently coded by two researchers, and analyzed per a grounded theory approach adapted to the Social Cognitive Theory framework. The research team reviewed transcripts and coding to reach consensus on emergent themes. Results N = 33 adults with OUD (28 male, 5 female) completed a single individual interview. Purposeful sampling recruited persons leaving jail on XR-NTX (n = 11), no active medication treatment (n = 9), methadone (n = 9), and buprenorphine (n = 4). Emergent themes were: (1) general satisfaction with XR-NTX’s long-acting antagonist effects and control of cravings; (2) “testing” XR-NTX’s blockade with heroin upon reentry was common; (3) early discontinuation of XR-NTX treatment was most common among persons with high self-efficacy and/or heavy exposure to drug use environments and peers; (4) similar satisfaction regarding effects of methadone and buprenorphine maintenance among retained-in-treatment individuals, alongside general dissatisfaction with daily observed dosing requirements and misinformation and stigmas regarding methadone adverse effects; (5) unstable housing, economic insecurity, and exposure to actively using peers were attributed to early termination of treatment and relapse; (6) individual motivation and willpower as central to long-term opioid abstinence and reentry success. Conclusions In the context of more familiar agonist maintenance treatments, XR-NTX relapse prevention during jail-to-community reentry was viewed as a helpful and unique intervention though with important limitations. Commonly described barriers to treatment retention and heroin abstinence included homelessness, economic insecurity, and drug-using peers. Trial registration ClinicalTrials.gov, NCT01999946 (XOR), Registered 03 December 2013, https://clinicaltrials.gov/ct2/show/NCT01999946 .

Background Extended-release buprenorphine (XRB) offers a novel approach to sustained monthly treatment for people who use opioids in criminal justice settings (CJS). This study explores the experiences of adults receiving XRB as a jail-to-community treatment. Methods and findings In-depth qualitative interviews were conducted among adult participants with opioid use disorder (OUD; n  = 16) who were recently released from NYC jails and maintained on XRB after switching from daily sublingual buprenorphine (SLB). Interviews elaborated on the acceptability and barriers and facilitators of XRB treatment pre- and post-release. Interviews were audio recorded, transcribed, and analyzed for content related to factors influencing XRB treatment uptake and community reentry. Important themes were grouped into systems, medication, and patient-level factors. Key systems-level factors influencing initiation of XRB in jail included an alternative to perceived stigmatization and privacy concerns associated with daily in-jail SLB administration and less concerns with buprenorphine diversion. In-jail peer networks positively influenced participant adoption of XRB. XRB satisfaction was attributed to reduced in-jail clinic and medication administration visits, perceived efficacy and blockade effects upon the use of heroin/fentanyl following release, and averting the risk of criminal activities to fund opioid use. Barriers to retention included post-injection withdrawal symptoms and cravings attributed to perceived suboptimal medication dosing, injection site pain, and lack of in-jail provider information about the medication. Conclusion Participants were generally favorable to XRB initiation in jail and retention post-release. Further studies are needed to address factors influencing access to XRB in criminal justice settings, including stigma, ensuring patient privacy following initiation on XRB, and patient-, provider-, and correctional staff education pertaining to XRB. Trial Registration ClinicalTrials.gov Identified: NCT03604159.

Our intuitive understanding of adaptation by natural selection is dominated by the power of selection at early ages in large populations. Yet, as the forces of natural selection fall with adult age, we expect adaptation to be attenuated with age. Explicit simulations of age-dependent adaptation suggest that populations adapt to a novel environment quickly at early ages, but only slowly and incompletely at later adult ages. Experimental tests for age-dependent adaptation to a novel diet were performed on populations of Drosophila melanogaster. The results support the prediction that populations should perform better on an ancestral, long-abandoned diet, compared to an evolutionarily recent diet, only at later ages. D. melanogaster populations also perform poorly on a novel diet compared to an evolutionarily recent diet that has been sustained for hundreds of generations, particularly at earlier ages. Additional experiments demonstrate that the timing of the shift to better performance in our populations on the long-abandoned diet is dependent on when the forces of natural selection weaken in the evolutionary history of experimental populations. Taken together, these experimental findings suggest that the forces of natural selection scale the rate of adaptation to novel environments.

A new volume in the bestselling Pocket Notebook series, Pocket Addiction Medicine delivers highly relevant coverage of this widespread and increasing health care problem in an easily portable source.Edited by physician leaders in Addiction Medicine, Drs.Sarah E.Wakeman, Joshua D.

Background Engagement in the HIV care continuum combined with office-based opioid treatment remains a cornerstone in addressing the intertwined epidemics of opioid use disorder (OUD) and HIV/AIDS. Factors influencing patient engagement with OUD and HIV care are complex and require further study. Methods In this qualitative study, in-depth interviews were conducted among 23 adult patients who use drugs (PWUD) in an inpatient detoxification program in New York City. The semi-structured interview guide elicited participant experiences with various phases of the HIV care continuum, including factors influencing access to HIV care, interactions with HIV and primary care providers, preferences around integrated care approaches for OUD and HIV, and barriers experienced beyond clinical settings which affected access to HIV care (e.g., insurance issues, transportation, cost, retrieving prescriptions from their pharmacy). Data collection and thematic analysis took place concurrently using an iterative process-based established qualitative research method. Results Respondents elicited high acceptability for integrated or co-located care for HIV and OUD in primary care. Factors influencing engagement in HIV care included (1) access to rapid point-of-care HIV testing and counseling services, (2) insurance coverage and costs related to HIV testing and receipt of antiretroviral therapy (ART), (3) primary care providers offering HIV care and buprenorphine, (4) illicit ART sales to pharmacies, (5) disruption in supplies of ART following admissions to inpatient detoxification or residential treatment programs, (6) in-person and telephone contact with peer support networks and clinic staff, (7) stigma, and (8) access to administrative support in primary care to facilitate reengagement with care following relapse, behavioral health services, transportation vouchers, and relocation from subsidized housing exposing patients to actively using peers. Conclusion These findings suggest expanding clinical and administrative support in primary care for PWUDs with patient navigators, case managers, mobile health interventions, and peer support networks to promote linkage and retention in care.