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Lyman-alpha emission is one of the observational probes for the high-redshift universe. Here, the authors show several Lyman-alpha emitting companion galaxies around the hot dust-obscured galaxy W0410-091 suggesting that the galaxy evolves in a very dense environment.

Abstract Background miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact of miR-346 on DNA damage, and its potential as a therapeutic agent. Methods RNA-IP, RNA-seq, RNA-ISH, DNA fibre assays, in vivo xenograft studies and bioinformatics approaches were used alongside a novel method for amplification-free, single nucleotide-resolution genome-wide mapping of DNA breaks (INDUCE-seq). Results miR-346 induces rapid and extensive DNA damage in PC cells - the first report of microRNA-induced DNA damage. Mechanistically, this is achieved through transcriptional hyperactivation, R-loop formation and replication stress, leading to checkpoint activation and cell cycle arrest. miR-346 also interacts with genome-protective lncRNA NORAD to disrupt its interaction with PUM2, leading to PUM2 stabilisation and its increased turnover of DNA damage response (DDR) transcripts. Confirming clinical relevance, NORAD expression and activity strongly correlate with poor PC clinical outcomes and increased DDR in biopsy RNA-seq studies. In contrast, miR-346 is associated with improved PC survival. INDUCE-seq reveals that miR-346-induced DSBs occur preferentially at binding sites of the most highly-transcriptionally active transcription factors in PC cells, including c-Myc, FOXA1, HOXB13, NKX3.1, and importantly, AR, resulting in target transcript downregulation. Further, RNA-seq reveals widespread miR-346 and shNORAD dysregulation of DNA damage, replication and cell cycle processes. NORAD drives target-directed miR decay (TDMD) of miR-346 as a novel genome protection mechanism: NORAD silencing increases mature miR-346 levels by several thousand-fold, and WT but not TDMD-mutant NORAD rescues miR-346-induced DNA damage. Importantly, miR-346 sensitises PC cells to DNA-damaging drugs including PARP inhibitor and chemotherapy, and induces tumour regression as a monotherapy in vivo, indicating that targeting miR-346:NORAD balance is a valid therapeutic strategy. Conclusions A balancing act between miR-346 and NORAD regulates DNA damage and repair in PC. miR-346 may be particularly effective as a therapeutic in the context of decreased NORAD observed in advanced PC, and in transcriptionally-hyperactive cancer cells.

Aims: The aim of this study was to perform a systematic review and bias evaluation of the current literature to create an overview of risk factors for re-revision following revision total knee arthroplasty (rTKA). Methods: A systematic search of MEDLINE and Embase was completed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The studies were required to include a population of index rTKAs. Primary or secondary outcomes had to be re-revision. The association between preoperative factors and the effect on the risk for re-revision was also required to be reported by the studies. Results: The search yielded 4,847 studies, of which 15 were included. A majority of the studies were retrospective cohorts or registry studies. In total, 26 significant risk factors for re-revision were identified. Of these, the following risk factors were consistent across multiple studies: age at the time of index revision, male sex, index revision being partial revision, and index revision due to infection. Modifiable risk factors were opioid use, BMI > 40 kg/m2, and anaemia. History of one-stage revision due to infection was associated with the highest risk of re-revision. Conclusion: Overall, 26 risk factors have been associated with an increased risk of re-revision following rTKA. However, various levels of methodological bias were found in the studies. Future studies should ensure valid comparisons by including patients with identical indications and using clear definitions for accurate assessments. Cite this article: Bone Jt Open 2024;5(8):644–651.

Abstract Background People incarcerated in jails are highly impacted by the opioid epidemic, and overdose education and naloxone distribution (OEND) is an effective strategy to reduce opioid overdose deaths. This study examines barriers and facilitators of fast-track OEND implementation within the jails in the Wave 1 Kentucky counties of the HEALing Communities Study during the COVID-19 pandemic. Methods Meeting minutes with jail stakeholders were qualitatively coded using the Practical, Robust Implementation and Sustainability Model (PRISM) as the coding framework. The analysis highlighted the top barriers and facilitators to fast-track OEND implementation within the PRISM framework. Results Space and staffing shortages related to the COVID-19 pandemic, disruptions in interorganizational programming from pandemic-related service suspensions, and a lack of technological solutions (e.g., reliable Internet access) for socially distanced delivery were the top barriers to fast-track OEND implementation. In addition, there were limitations on non-jail staff access to jails during COVID-19. Top facilitators included jail leadership support, the option to prioritize high-risk groups, and the incorporation of OEND processes into existing communications and management software. While the COVID-19 pandemic strained jail infrastructure, jail and partner agency collaboration led to creative implementation strategies for the successful integration of OEND into jail operations. Urban jails were more likely than rural jails to be early adopters of OEND during the public health emergency. Conclusions Understanding the barriers to and facilitators of OEND within jails will improve implementation efforts seeking to curb opioid overdose deaths. Jail leadership support and interorganizational efforts were key facilitators to implementation; therefore, it is recommended to increase buy-in with multiple agencies to promote success. Challenges brought on by COVID-19 have resulted in a need for innovative solutions for implementation. Clinical trial information ClinicalTrials.gov, NCT04111939, Submitted 30 September 2019, https://clinicaltrials.gov/study/NCT04111939?titles=HEALing%20Communities%20Study&rank=1 .

Abstract Background Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations. Methods This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12–25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant’s electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants’ perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.). Discussion This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA. ClinicalTrials.gov NCT06275191.

We present JWST NIRCam imaging targeting 13 z ~ 3 infrared-luminous ( L _IR ∼ 5 × 10 ^12 L _⊙ ) galaxies from the ALESS survey with uniquely deep, high-resolution (0 $\mathop{.}\limits^{\unicode{x02033}}$ 08–0 $\mathop{.}\limits^{^{\prime\prime} }$ 16) Atacama Large Millimeter/submillimeter Array 870 μ m imaging. The 2.0–4.4 μ m (observed frame) NIRCam imaging reveals the rest-frame near-infrared stellar emission in these submillimeter-selected galaxies at the same (sub)kiloparsec resolution as the 870 μ m dust continuum. The newly revealed stellar morphologies show striking similarities with the dust continuum morphologies at 870 μ m, with the centers and position angles agreeing for most sources, clearly illustrating that the spatial offsets reported previously between the 870 μ m and Hubble Space Telescope morphologies were due to strong differential dust obscuration. The F444W sizes are 78% ± 21% larger than those measured at 870 μ m, in contrast to recent results from hydrodynamical simulations that predict larger 870 μ m sizes. We report evidence for significant dust obscuration in F444W for the highest-redshift sources, emphasizing the importance of longer-wavelength MIRI imaging. The majority of the sources show evidence that they are undergoing mergers/interactions, including tidal tails/plumes—some of which are also detected at 870 μ m. We find a clear correlation between NIRCam colors and 870 μ m surface brightness on ∼1 kpc scales, indicating that the galaxies are primarily red due to dust—not stellar age—and we show that the dust structure on ∼kpc scales is broadly similar to that in nearby galaxies. Finally, we find no strong stellar bars in the rest-frame near-infrared, suggesting the extended bar-like features seen at 870 μ m are highly obscured and/or gas-dominated structures that are likely early precursors to significant bulge growth.

Abstract Background The COVID-19 pandemic produced system-level changes within the criminal legal system and community-based substance use disorder (SUD) treatment system with impacts on recovery efforts. This study examines rural and urban clinicians’ perspectives of COVID-19 on SUD treatment delivery for people on community supervision. Methods Virtual qualitative interviews were conducted between April and October 2020 with 25 community supervision clinicians employed by Kentucky’s Department of Corrections (DOC), who conduct assessments and facilitate community-based treatment linkages for individuals on probation or parole. Transcripts were analyzed in NVivo using directed content analysis methods. Results Clinicians were predominantly white (92%) and female (88%) with an average of over 9 years working in the SUD treatment field and 4.6 years in their current job. Four COVID-19 themes were identified by both rural and urban clinicians including: (1) telehealth increases the modes of communication, but (2) also creates paperwork and technological challenges, (3) telehealth requires more effort for inter/intra-agency collaboration, and (4) it limits client information (e.g., no urine drug screens). Two additional rural-specific themes emerged related to COVID-19: (5) increasing telehealth options removes SUD treatment transportation barriers and (6) requires flexibility with programmatic requirements for rural clients. Conclusions Findings indicate the need for community-based SUD treatment providers approved or contracted by DOC to support and train clients to access technology and improve information-sharing with community supervision officers. A positive lesson learned from COVID-19 transitions was a reduction in costly travel for rural clients, allowing for greater engagement and treatment adherence. Telehealth should continue to be included within the SUD continuum of care, especially to promote equitable services for individuals from rural areas.

Abstract Background Scaling up overdose education and naloxone distribution (OEND), an evidence-based practice for reducing opioid overdose mortality, in communities remains a challenge. Novel models and intentional implementation strategies are needed. Drawing upon the EPIS model’s phases of Exploration, Preparation, Implementation, and Sustainment (Aarons et al. in Adm Policy Ment Health 38:4–23, 2011), this paper describes the development of the University of Kentucky’s unique centralized “Naloxone Hub with Many Spokes” approach to implementing OEND as part of the HEALing Communities Study (HCS-KY). Methods To scale up OEND in eight Kentucky counties, implementation strategies were utilized at two levels: a centralized university-based naloxone dispensing unit (“Naloxone Hub”) and adopting organizations (“Many Spokes”). Implementation strategies varied across the EPIS phases, but heavily emphasized implementation facilitation. The Naloxone Hub provided technical assistance, overdose education resources, and no-cost naloxone to partner organizations. Implementation outcomes across the EPIS phases were measured using data from internal study management trackers and naloxone distribution data submitted by partner organizations. Results Of 209 organizations identified as potential partners, 84.7% (n = 177) engaged in the Exploration/Preparation phase by participating in an initial meeting with an Implementation Facilitator about the HCS-KY OEND program. Adoption of the HCS-KY OEND program, defined as receipt of at least one shipment of naloxone, was achieved with 69.4% (n = 145) of all organizations contacted. During the Implementation phase, partner organizations distributed 40,822 units of naloxone, with partner organizations distributing a mean of 281.5 units of naloxone (SD = 806.2). The mean number of units distributed per county was 5102.8 (SD = 3653.3; range = 1057 − 11,053) and the mean county level distribution rate was 8396.5 units per 100,000 residents (SD = 8103.1; range = 1709.5–25,296.3). Of the partner organizations that adopted the HCS-KY OEND program, 87.6% (n = 127) attended a sustainability meeting with an Implementation Facilitator and agreed to transition to the state-funded naloxone program. Conclusions These data demonstrate the feasibility of this “Hub with Many Spokes” model for scaling up OEND in communities highly affected by the opioid epidemic. Trial registration ClinicalTrials.gov, NCT04111939. Registered 30 September 2019, https://clinicaltrials.gov/ct2/show/NCT04111939 .

Summary: Background: Community stigma against people with opioid use disorder (OUD) and intervention stigma (e.g., toward naloxone) exacerbate the opioid overdose crisis. We examined the effects of the Communities that HEAL (CTH) intervention on perceived opioid-related community stigma by stakeholders in the HEALing Communities Study (HCS). Methods: We collected three surveys from community coalition members in 66 communities across four states participating in HCS. Communities were randomized into Intervention (Wave 1) or Wait-list Control (Wave 2) arms. We conducted multilevel linear mixed models to compare changes in primary outcomes of community stigma toward people treated for OUD, naloxone, and medication for opioid use disorder (MOUD) by arm from time 1 (before the start of the intervention) to time 3 (end of the intervention period in the Intervention arm). Findings: Intervention stakeholders reported a larger decrease in perceived community stigma toward people treated for OUD (adjusted mean change (AMC) −3.20 [95% C.I. −4.43, −1.98]) and toward MOUD (AMC −0.33 [95% C.I. −0.56, −0.09]) than stakeholders in Wait-list Control communities (AMC −0.18 [95% C.I. −1.38, 1.02], p = 0.0007 and AMC 0.11 [95% C.I. −0.09, 0.31], p = 0.0066). The relationship between intervention status and change in stigma toward MOUD was moderated by rural-urban status (urban AMC −0.59 [95% CI, −0.87, −0.32], rural AMC not sig.) and state. The difference in stigma toward naloxone between Intervention and Wait-list Control stakeholders was not statistically significant (p = 0.18). Interpretation: The CTH intervention decreased stakeholder perceptions of community stigma toward people treated for OUD and stigma toward MOUD. Implementing the CTH intervention in other communities could decrease OUD stigma across diverse settings nationally. Funding: US National Institute on Drug Abuse.

Background and purpose: Soft tissue defects after total knee arthroplasties (TKA) represent a major orthopedic challenge with amputation as a feared outcome. Microvascular free flap coverage (FFC) can increase limb salvage rates, but complications related to the procedure are yet to be explored further. We aimed to review a single-center experience with FFC for soft tissue defects related to revision total knee arthroplasty. Methods: Through a retrospective chart review from 2006 to 2021, we identified all patients who had FFC of a knee with an existing TKA. Typically, patients underwent 2-stage revision arthroplasty. To identify areas of intervention, we divided the entire regimen into 2 phases divided by the free flap surgery (pre- and post-free flap). Results: We identified 18 patients with a median age at free flap surgery of 69 years (range 39–85), who were followed for a median of 5.1 years (range 2 months to 10.6 years). The median duration from primary TKA to their final operation was 17.5 months (range 19 days to 7 years). Patients underwent a mean of 7.6 surgical procedures on their knee with 3.6 orthopedic revisions prior to the FFC and 0.6 after. Soft tissue coverage was achieved in all patients and no patients underwent amputation. One-third of patients experienced early complications at recipient site after free flap surgery. There were no donor site complications. Conclusion: Microvascular FFC of complex soft tissue defects after revision total knee arthroplasty proved achievable in all patients with successful limb salvage in all patients.

Background: Opioid overdoses differentially affect demographic groups. Strategies to reduce overdose deaths, specifically overdose education and naloxone distribution (OEND), are not consistently delivered equitably. Methods: The HEALing Communities StudySM (HCS) is a cluster-randomized trial designed to implement evidence-based practices, including OEND, to reduce overdose deaths across communities. Individuals receiving OEND in eight Kentucky counties between January 2020 and June 2022 provided demographics and overdose history. Recipient characteristics were compared to opioid overdose decedent characteristics to evaluate whether OEND was equitably delivered to the target population. Recipient characteristics were also analyzed based on whether OEND was delivered in criminal justice, behavioral health, or health care facilities. Results: A total of 26,273 demographic records were analyzed from 137 partner agencies. Most agencies were in behavioral health (85.6 %) or criminal justice sectors (10.4 %). About half of OEND recipients were male (50.6 %), which was significantly lower than the 70.3 % of overdose decedents who were male, (p

We present a statistical study of 180 dust continuum sources identified in 33 massive cluster fields by the Atacama Large Millimeter/submillimeter Array Lensing Cluster Survey (ALCS) over a total of 133 arcmin ^2 area, homogeneously observed at 1.2 mm. ALCS enables us to detect extremely faint millimeter sources by lensing magnification, including near-infrared (NIR) dark objects showing no counterparts in existing Hubble Space Telescope and Spitzer images. The dust continuum sources belong to a blind sample ( N = 141) with signal-to-noise ratio (S/N) ≳ 5.0 (a purity of >0.99) or a secondary sample ( N = 39) with S/N = 4.0–5.0 screened by priors. With the blind sample, we securely derive 1.2 mm number counts down to ∼7 μ Jy, and find that the total integrated 1.2 mm flux is ${20.7}_{-6.5}^{+8.5}$ Jy deg ^−2 , resolving ≃80% of the cosmic infrared background light. The resolved fraction varies by a factor of 0.6–1.1 due to the completeness correction depending on the spatial size of the millimeter emission. We also derive infrared (IR) luminosity functions (LFs) at z = 0.6–7.5 with the $1/{V}_{\max }$ method, finding the redshift evolution of IR LFs characterized by positive luminosity and negative density evolution. The total (= UV + IR) cosmic star formation rate density (SFRD) at z > 4 is estimated to be ${161}_{-21}^{+25}$ % of the Madau and Dickinson measurements mostly based on rest-frame UV surveys. Although our general understanding of the cosmic SFRD is unlikely to change beyond a factor of 2, these results add to the weight of evidence for an additional (≈60%) SFRD component contributed by the faint millimeter population, including NIR-dark objects.

We present a UV to millimeter spectral energy distribution (SED) analysis of 16 hyperluminous, dust-obscured quasars at z ∼ 3, selected by the Wide-field Infrared Survey Explorer. We aim to investigate the physical properties of these quasars, with a focus on their molecular gas content. We decompose the SEDs into three components: stellar, cold dust, and active galactic nucleus (AGN). By doing so, we are able to derive and analyze the relevant properties of each component. We determine the molecular gas mass from CO line emission based on Atacama Large Millimeter/submillimeter Array (ALMA) observations. By including ALMA observations in the multiwavelength SED analysis, we derive the molecular gas fractions, gas depletion timescales, and star formation efficiencies (SFEs). Their sample median and 16th–84th quartile ranges are ${f}_{\mathrm{gas}}\,\sim \,{0.33}_{-0.17}^{+0.33}$ , t _depl ∼ ${39}_{-28}^{+85}$ Myr, and SFE ∼ ${297}_{-195}^{+659}$ K km s ^−1 pc ^−2 , respectively. Compared to main-sequence galaxies, they have lower molecular gas content and higher SFEs, similar to quasars in the literature. This suggests that the gas in these quasars is rapidly depleted, likely as the result of intense starburst activity and AGN feedback. The observed correlations between these properties and the AGN luminosities further support this scenario. Additionally, we infer the black hole to stellar mass ratio and black hole mass growth rate, which indicate significant central black hole mass assembly over short timescales. Our results are consistent with the scenario that our sample represents a short transition phase toward unobscured quasars.

Background: A major part of the HEALing Communities Study (HCS), launched in 2019 to address the growing opioid epidemic, is evaluating the study’s intervention implementation process through an implementation science (IS) approach. One component of the IS approach involves teams with more than 20 researchers collaborating across four research sites to conduct in-depth qualitative interviews with over 300 participants at four time points. After completion of the first two rounds of data collection, we reflect upon our qualitative data collection and analysis approach. We aim to share our lessons learned about designing and applying qualitative methods within an implementation science framework. Methods: The HCS evaluation is based on the RE-AIM/PRISM framework and incorporates interviews at four timepoints. At each timepoint, the core qualitative team of the Intervention Work Group drafts an interview guide based on the framework and insights from previous round(s) of data collection. Researchers then conduct interviews with key informants and coalition members within their respective states. Data analysis involves drafting, iteratively refining, and finalizing a codebook in a cross-site and within-site consensus processes. Interview transcripts are then individually coded by researchers within their respective states. Results: Successes in the evaluation process include having structured procedures for communication, data collection, and analysis, all of which are critical for ensuring consistent data collection and for achieving consensus during data analysis. Challenges include recognizing and accommodating the diversity of training and knowledge among researchers, as well as establishing reliable ways to securely store, manage, and share the large volumes of data. Conclusion: Qualitative methods using a Team Science approach have been limited in their application in large, multi-site randomized controlled trials of health interventions. Our experience provides practical guidance for future studies with large teams that are experientially and disciplinarily diverse and that are seeking to incorporate qualitative or mixed-methods components for their evaluations.

Abstract Background Expanding access to medications for opioid use disorder (MOUD), such as buprenorphine and extended release (XR) naltrexone, is critical to addressing the US opioid epidemic, but little is known about prescriber satisfaction with delivering these two types of MOUD. The current study describes the satisfaction of prescribers delivering buprenorphine and XR-naltrexone while examining whether satisfaction is associated with current patient census and organizational environment. Methods As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 41 MOUD prescribers in Florida, Ohio, and Wisconsin completed a web-based survey. The survey included measures of prescriber satisfaction with delivering buprenorphine treatment and XR-naltrexone. In addition, the survey measured several prescriber characteristics and their perceptions of the organizational environment. Results Prescribers were generally satisfied with their work in delivering these two types of MOUD. Prescribers reporting a greater number of patients (r = .46, p = .006), those who would recommend the center to others (r = .56, p < .001), and those reporting positive relationships with staff (r = .56, p < .001) reported significantly greater overall satisfaction with delivering buprenorphine treatment. Prescribers who more strongly endorsed feeling overburdened reported lower overall buprenorphine satisfaction (r = -.37, p = .02). None of the prescriber characteristics or perceptions of the organizational environment were significantly associated with overall satisfaction with delivering XR-naltrexone treatment. Conclusions The generally high levels of satisfaction with both types of MOUD is notable given that prescriber dissatisfaction can lead to turnover and impact intentions to leave the profession. Future research should continue to explore the prescriber characteristics and organizational factors associated with satisfaction in providing different types of MOUD. Registration ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482 .

Abstract Background Despite a growing body of empirical support for the effectiveness of extended-release naltrexone (XR-NTX) to reduce opioid relapse among people with opioid use disorder (OUD) transitioning from a correctional facility to the community, continuity of care following release remains challenging. This paper describes a research-based adaptation of a state’s standard of care XR-NTX protocol using the ADAPT-ITT framework for delivery in a non-traditional, non-treatment, community criminal justice setting (P&P office), as well as the expansion of services by a local Federally Qualified Health Center (FQHC) provider who would, for the first time, be going to the jail and P&P office to provide XR-NTX and related treatment. Method The present study focuses on the first seven phases (Assessment through Training) of the ADAPT-ITT framework in the adaptation of the Department of Corrections (DOC) protocol in preparation for a pilot trial for induction in a rural jail and during the transition to a rural community. Expert clinical review and focus groups with key stakeholders in criminal justice supervision and the local providers in the FQHC informed the needed adaptations to the existing XR-NTX protocol for initiation at the jail and ongoing administrations in the community. Results Findings from stakeholder focus groups, study team review, topical expert review, and a theater test suggested that there were critical adaptations needed in both content and context at the patient and clinic level. Conclusion Health and justice officials should consider the need to tailor and adapt evidence-based approaches for real-world locations that high-risk, justice-involved individuals visit in order to reduce barriers and increase access to critically needed treatment for OUD.

Abstract Background This study examined the national availability of substance use prevention (SUP) within juvenile justice (JJ) and their primary behavioral health (BH) providers, and the relationships between the availability of SUP and agency-level measures of organizational structure, staffing, and youth characteristics. A three-stage national probability sampling process was used to select participants for a national survey that included, among other facets of community supervision (CS) and BH practices, questions on agency characteristics, youth characteristics, whether the agency/provider directly provided SUP services, and whether the agency/provider directly provided substance use and/or mental health treatment. This paper focuses on SUP services along with agency/provider and youth characteristics related to providing SUP. Results The response rate for both CS agencies (n = 195) and BH providers (n = 271) was 96%. Complex samples logistic regression initially examined univariate associations of each variable and identified candidates for a final multivariate model. Overall, only one-third of CS and BH providers reported offering SUP services, with BH providers being significantly more likely than CS agencies to provide SUP services. In addition, likelihood of SUP was significantly lower among agencies where the substance use distribution of the caseload was below the median. Controlling for master’s level staff and the substance use distribution, CS agencies were about 67% less likely to offer SUP when compared to BH providers. Conclusions Given the high rates of substance use among justice-involved youth and that substance use is an established risk for several negative behaviors, outcomes, and health conditions, these findings suggest that evidence-based prevention services should likely be expanded in justice settings, and perhaps included as part of CS programs, even when youth do not initially present with SU service needs.

Appalachian Kentucky was at the epicenter of the prescription opioid epidemic in the early 2000's. As we enter the third decade of the epidemic, patterns have begun to emerge as people who use drugs (PWUD) transition from use of opioids to other drugs. The purpose of this analysis was to examine longitudinal changes in methamphetamine use in an ongoing cohort of rural people who use drugs (PWUD) in Appalachian Kentucky. All but five of the cohort participants (N = 503) reported nonmedical prescription opioid use (NMPOU) at baseline and those 498 are included in this longitudinal analysis encompassing eight waves of data (2008–2020). Past 6-month use of methamphetamine was the dependent variable. Given the correlated nature of the data, mixed effects logistic regression was utilized to examine changes in methamphetamine use over time. Significant increases in methamphetamine use were observed over the past decade in this cohort of PWUD, especially in recent years (2017–2020). Prevalence of recent use at baseline and each of the follow-up visits was as follows: 9.4, 5.6, 5.0, 5.4, 8.1, 6.8, 6.9, and 33.1%, respectively (p < 0.001). On the contrary, significant reductions in NMPO and heroin use were observed in the same time period. The odds of methamphetamine use at the most recent visit were 25.8 times greater than at baseline (95% CI: 14.9, 44.6) and 52.6% of those reporting methamphetamine use reported injecting the drug. These results provide further evidence of “twin epidemics” of methamphetamine use among NMPOU. While problematic on several fronts, of particular concern is the lack of effective treatment options for methamphetamine use disorder. As policies around the opioid epidemic continue to evolve, particular attention should be paid to the surge in stimulant use in opioid-endemic areas.

Abstract Objective The aim of this cross-sectional study was to investigate the cortical metabolite concentrations in patients suffering from migraine with aura (MWA). We hypothesized that occipital γ-aminobutyric acid (GABA) levels are lower in MWA patients. Background Recent studies have indicated that a disturbance in the inhibitory GABA is involved in triggering the migraine aura. We aimed to explore this using a novel magnetic resonance spectroscopy sequence. Methods Using spin echo full intensity acquired localized spectroscopy on a Siemens 3 Tesla magnetic resonance scanner, we obtained occipital and parietal metabolite concentrations in 14 patients suffering from migraine with aura and a group of 16 matched healthy subjects. All scans were performed at Aarhus University Hospital, at the Center for Functionally Integrative Neuroscience (CFIN). Results No difference was found in GABA/(Total creatine) levels in either the occipital cortex (p = 0.744) or in the somatosensory cortex (p = 0.305). Conclusion These findings indicate that cortical GABA levels are normal in patients suffering from relatively few migraine attacks. Previous studies have reported that cortical GABA in patients with more frequent migraines is reduced; further investigation of the inhibitory system in migraine patients is warranted to determine the underlying mechanisms.

Abstract Background Opioid use disorder (OUD) is a major risk factor in the acquisition and transmission of HIV. Clinical practice guidelines call for the integration of HIV services in OUD treatment. This mixed methods study describes the integration of HIV services in buprenorphine treatment and examines whether HIV services vary by prescribers’ medical specialty and across practice settings. Methods Data were obtained via qualitative interviews with buprenorphine experts (n = 21) and mailed surveys from US buprenorphine prescribers (n = 1174). Survey measures asked about screening for HIV risk behaviors at intake, offering HIV education, recommending all new patients receive HIV testing, and availability of on-site HIV testing. Prescribers’ medical specialty, practice settings, caseload demographics, and physician demographics were measured. Multivariate models of HIV services were estimated, while accounting for the nesting of physicians within states. Results Qualitative interviews revealed that physicians often use injection behaviors as the primary indicator for whether a patient should be tested for HIV. Interviews revealed that HIV-related services were often viewed as beyond the scope of practice among general psychiatrists. Surveys indicated that prescribers screened for an average of 3.2 of 5 HIV risk behaviors (SD = 1.6) at intake. About 62.0% of prescribers delivered HIV education to patients and 53.2% recommended HIV testing to all new patients, but only 32.3% offered on-site HIV testing. Addiction specialists and psychiatrists screened for significantly more HIV risk behaviors than physicians in other specialties. Addiction specialists and psychiatrists were significantly less likely than other physicians to offer on-site testing. Physicians in individual medical practice were significantly less likely to recommend HIV testing and to offer onsite testing than physicians in other settings. Conclusions Buprenorphine treatment providers have not uniformly integrated HIV-related screening, education, and testing services for patients. Differences by medical specialty and practice setting suggest an opportunity for targeting efforts to increase implementation.

Two high-mass polar compounds were observed in aqueous side-fractions from the purification of okadaic acid (1) and dinophysistoxin-2 (2) from Dinophysis blooms in Spain and Norway. These were isolated and shown to be 24-O-β-d-glucosides of 1 and 2 (4 and 5, respectively) by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and enzymatic hydrolysis. These, together with standards of 1, 2, dinophysistoxin-1 (3), and a synthetic specimen of 7-deoxy-1 (7), combined with an understanding of their mass spectrometric fragmentation patterns, were then used to identify 1–5, the 24-O-β-d-glucoside of dinophysistoxin-1 (6), 7, 7-deoxy-2 (8), and 7-deoxy-3 (9) in a range of extracts from Dinophysis blooms, Dinophysis cultures, and contaminated shellfish from Spain, Norway, Ireland, Canada, and New Zealand. A range of Prorocentrum lima cultures was also examined by liquid chromatography–high resolution tandem mass spectrometry (LC–HRMS/MS) and was found to contain 1, 3, 7, and 9. However, although 4–6 were not detected in these cultures, low levels of putative glycosides with the same exact masses as 4 and 6 were present. The potential implications of these findings for the toxicology, metabolism, and biosynthesis of the okadaic acid group of marine biotoxins are briefly discussed.

Volatiles emitted by plants convey an array of information through different trophic levels. Animals such as host-seeking herbivores encounter plumes with filaments from both host and non-host plants. While studies showed a behavioral effect of non-host plants on herbivore host location, less information is available on how a searching insect herbivore perceives and flies upwind to a host-plant odor plume within a background of non-host volatiles. We hypothesized here that herbivorous insects in search of a host-plant can discriminate plumes of host and non-host plants and that the taxonomic relatedness of the non-host have an effect on finding the host. We also predicted that the ratio between certain plant volatiles is cognized as host-plant recognition cue by a receiver herbivorous insect. To verify these hypotheses we measured the wind tunnel response of the moth Argyresthia conjugella to the host plant rowan, to non-host plants taxonomically related (Rosaceae, apple and pear) or unrelated to the host (Pinaceae, spruce) and to binary combination of host and non-host plants. Volatiles were collected from all plant combinations and delivered to the test insect via an ultrasonic sprayer as an artificial plume. While the response to the rowan as a plant was not affected by the addition of any of the non-host plants, the attraction to the corresponding sprayed headspace decreased when pear or apple but not spruce were added to rowan. A similar result was measured toward the odor exiting a jar where freshly cut plant material of apple or pear or spruce was intermixed with rowan. Dose-response gas-chromatography coupled to electroantennography revealed the presence of seven field attractive and seven background non-attractive antennally active compounds. Although the abundance of field attractive and of some background volatiles decreased in all dual combinations in comparison with rowan alone, an increased amount of the background compounds (3E)-4,8-Dimethyl-1,3,7-nonatriene ((E)-DMNT) and (Z)-3-hexenyl acetate was found in the rowan-apple and rowan-pear but not in the rowan-spruce headspace. A higher ratio between the abundance of each field attractive component and that of (E)-DMNT and (Z)-3-hexenyl acetate was measured for rowan and rowan-spruce in contrast to rowan-pear and rowan-apple headspaces. Our result suggests that the ratio between field attractive and background antennaly active volatiles encodes host-plant recognition in our study system.