Hypertrophic cardiomyopathy-associated mutations drive stromal activation via EGFR-mediated paracrine signaling.

Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the left ventricular wall, diastolic dysfunction, and fibrosis, and is associated with mutations in genes encoding sarcomere proteins. While in vitro studies have used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study HCM, these models have not examined the multicellular interactions involved in fibrosis. Using engineered cardiac microtissues (CMTs) composed of HCM-causing MYH7-variant hiPSC-CMs and wild-type fibroblasts, we observed cell-cell cross-talk leading to increased collagen deposition, tissue stiffening, and decreased contractility dependent on fibroblast proliferation. hiPSC-CM conditioned media and single-nucleus RNA sequencing data suggested that fibroblast proliferation is mediated by paracrine signals from MYH7-variant cardiomyocytes. Furthermore, inhibiting epidermal growth factor receptor tyrosine kinase with erlotinib hydrochloride attenuated stromal activation. Last, HCM-causing MYBPC3-variant CMTs also demonstrated increased stromal activation and reduced contractility, but with distinct characteristics. Together, these findings establish a paracrine-mediated cross-talk potentially responsible for fibrotic changes observed in HCM.

Outpatient management of pediatric epistaxis: A cost analysis and clinical model.

Objectives: Pediatric epistaxis is a common, often non-operative condition encountered by Otolaryngologists. The present study seeks to (1) describe our outcomes of epistaxis management, (2) estimate the associated healthcare burden, and (3) propose a clinical model to optimize care coordination with primary care and advanced practice providers. Methods: Retrospective case series of pediatric patients treated outpatient for epistaxis by a single otolaryngologist from 2021 to 2022. The primary outcome after treatment with nasal lubricants was defined as (1) refractory epistaxis, (2) improvement, or (3) complete resolution. Cost data for office versus operative nasal cautery were analyzed. Results: In total, 122 patients were included for analysis. Over a follow-up duration of 20.5 months (IQR 8-36), 24.6% of patients experienced refractory epistaxis, 41.8% of patients found improvement, and 33.6% had complete resolution (n = 122). Refractory epistaxis was associated with a family history of coagulopathy (p = .007), daily epistaxis episodes (p = .043), and anemia (p <.001). Average direct hospital costs associated with nasal cautery were $187 for in-office cauterization and $2179 for intraoperative cauterization. Estimated patient/third party payors savings were $1617 and $15,412 for in-office and intraoperative procedures, respectively, and $541.59 for specialty office visits alone. The average charge for laboratory work-up was $576. Conclusion: Approximately 75% of patients with epistaxis experienced improvement or resolution of symptoms with nasal lubrication alone. Refractory epistaxis was associated with a family history of coagulopathy, daily epistaxis episodes, and anemia. Otolaryngology visits for epistaxis were associated with a direct healthcare expense burden. Adaptation of our clinical model may mitigate these costs while improving patient care. Level of Evidence: 4.

Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease.

TMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied in vivo using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of TMEM106B in murine models of C9ORF72 -related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy and compare these to postmortem human tissue from patients with C9-ALS/FTD, Alzheimer's disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). We show that there are significant differences between TMEM106B pathology in mouse models and human patient tissue. Importantly, we also identified convergent evidence from both murine models and human patients that links TMEM106B pathology to TDP-43 nuclear clearance specifically in C9-ALS. Similarly, we find a relationship at the cellular level between TMEM106B pathology and phosphorylated Tau burden in Alzheimer's disease. By characterizing endogenous TMEM106B pathology in both mice and human postmortem tissue, our work reveals considerations that must be taken into account when analyzing data from in vivo mouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.

Photochemical Control of Network Topology in PEG Hydrogels.

Hydrogels are often synthesized through photoinitiated step-, chain-, and mixed-mode polymerizations, generating diverse network topologies and resultant material properties that depend on the underlying network connectivity. While many photocrosslinking reactions are available, few afford controllable connectivity of the hydrogel network. Herein, a versatile photochemical strategy is introduced for tuning the structure of poly(ethylene glycol) (PEG) hydrogels using macromolecular monomers functionalized with maleimide and styrene moieties. Hydrogels are prepared along a gradient of topologies by varying the ratio of step-growth (maleimide dimerization) to chain-growth (maleimide-styrene alternating copolymerization) network-forming reactions. The initial PEG content and final network physical properties (e.g., modulus, swelling, diffusivity) are tailored in an independent manner, highlighting configurable gel mechanics and reactivity. These photochemical reactions allow high-fidelity photopatterning and 3D printing and are compatible with 2D and 3D cell culture. Ultimately, this photopolymer chemistry allows facile control over network connectivity to achieve adjustable material properties for broad applications.

A Rare Presentation of Cryoglobulinemic Vasculitis Associated with Primary Sjögren's Syndrome.

INTRODUCTION: Sjögren's syndrome is a chronic autoimmune disorder that results in dry eyes and mouth. It is rarely associated with cryoglobulinemia, the agglutination of cryoglobulins at cold temperatures that leads to systemic inflammation and organ damage. We have, herein, presented a case of Cryoglobulinemic Vasculitis (CryoVas), which presents as cryoglobulinemic glomerulonephritis and Central Nervous System (CNS) vasculitis and peripheral neuropathy. CASE REPORT: A 52-year-old woman with a past medical history of Sjögren's syndrome was admitted to the intensive care unit with severe hyponatremia, orthopnea, and progressive lower extremity weakness, and was found to have an intradural extramedullary hematoma with mass effect in the thoracic spine and diffuse hyperintense cord signal abnormality in thoracic spine suggestive of intermixed proteinaceous or hemorrhagic material. Further testing demonstrated that the patient experienced worsening neuropathy, proteinuria, hematuria, declining renal function, and the presence of cryoglobulins in the blood. After a thorough examination and a renal biopsy, the patient was diagnosed with cryoglobulinemic glomerulonephritis and cryoglobulinemic vasculitis of the spine. The patient was treated with rituximab and pulse-dose steroids, with which the patient exhibited improved renal function and resolution of a previously seen intradural hematoma on repeat MRI. CONCLUSION: We have, herein, discussed a rare case of cryoglobulinemic vasculitis that has led to a rare CNS manifestation and concomitant cryoglobulinemic glomerulonephritis. This suggests that clinicians should consider cryoglobulinemic vasculitis as the etiology that could manifest with multiorgan involvement, especially in patients with underlying rheumatic diseases.

Experiences and access of palliative and end of life care for older people from minority ethnic groups: a scoping review.

BACKGROUND: Many older people from minority ethnic groups experience inequalities towards the end of life, including barriers to accessing palliative care. With levels of international migration increasing, there is a need to understand these differences and consider the needs of minority ethnic groups in healthcare policies. This review aimed to map evidence on how older people from minority ethnic groups access and utilise palliative and end of life care, preferences for palliative and end of life care, experiences of palliative and end of life care, and how this varies between minority ethnic groups in different countries, and with different health conditions. METHODS: Scoping review, following Joanna Briggs Institute (JBI) guidance. Searches of eight online databases (MEDLINE, Embase, Web of Science, CINAHL, PsycInfo, Assia, Scopus, and the Cochrane Library) and grey literature were undertaken in 2024. Qualitative sources that focused on older people from minority ethnic groups' and carers' access to and use of palliative and end of life care were included, as well as those focusing on healthcare professionals' experiences. RESULTS: Twenty-three sources were included in the review, the majority of which were interview studies from the USA. Findings reflect a range of preferences, inequalities, facilitators and barriers to accessing palliative and end of life care, with themes relating to: (1) Knowledge of hospice and palliative care, (2) societal and structural issues, (3) language and health literacy, (4) migratory experiences, (5) trust in healthcare services and professionals, (6) religion and hope, and (7) cultural values. CONCLUSIONS: This review identified areas for healthcare providers to consider developing more culturally appropriate palliative and end of life care practice, including building trust and improving communication, sharing information, reducing language barriers, addressing stigma, and, if relevant, acknowledging the importance of culture and religion. Further qualitative research from an intersectional perspective, such as geographical location or socio-economic status, rather than race, ethnicity, and culture alone, is needed in more diverse geographical settings and on specific health conditions.

Rapid Tissue Perfusion Using Sacrificial Percolation of Anisotropic Networks.

Tissue engineering has long sought to rapidly generate perfusable vascularized tissues with vessel sizes spanning those seen in humans. Current techniques such as biological 3D printing (top-down) and cellular self-assembly (bottom-up) are resource intensive and have not overcome the inherent tradeoff between vessel resolution and assembly time, limiting their utility and scalability for engineering tissues. We present a flexible and scalable technique termed SPAN - Sacrificial Percolation of Anisotropic Networks, where a network of perfusable channels is created throughout a tissue in minutes, irrespective of its size. Conduits with length scales spanning arterioles to capillaries are generated using pipettable alginate fibers that interconnect above a percolation density threshold and are then degraded within constructs of arbitrary size and shape. SPAN is readily used within common tissue engineering processes, can be used to generate endothelial cell-lined vasculature in a multi-cell type construct, and paves the way for rapid assembly of perfusable tissues.

Long-read RNA sequencing of archival tissues reveals novel genes and transcripts associated with clear cell renal cell carcinoma recurrence and immune evasion.

The use of long-read direct RNA sequencing (DRS) and PCR cDNA sequencing (PCS) in clinical oncology remains limited, with no direct comparison between the two methods. We used DRS and PCS to study clear cell renal cell carcinoma (ccRCC), focussing on new transcript and gene discovery. Twelve primary ccRCC archival tumors, six from patients who went on to relapse, were analysed. Results were validated in an independent cohort of twenty patients by qRT-PCR and compared to DRS analysis of RCC4 cells. In archival clinical samples and due to long-term storage, average read length was lower (400-500nt) than that achieved through DRS of RCC4 cells (>1100nt). Still, deconvolution analysis showed a loss of immune infiltrate in primary tumors of patients who relapse as reported by others. Differentially expressed genes in patients who went on to relapse were determined with good overlap between DRS and PCS, identifying LINC04216 and the T cell exhaustion marker TOX as novel candidate recurrence-associated genes. Novel transcript analysis revealed over 10,000 candidate novel transcripts detected by both methods and in ccRCC cells in vitro, including a novel CD274 (PD-L1) transcript encoding for the soluble version of the protein with a longer 3' UTR and lower stability than the annotated transcript. Both methods identified 414 novel genes, also detected in RCC4 cells, including a novel noncoding gene over-expressed in patients who relapse. Overall, we showcase use of PCS and DRS in archival tumor samples to uncover unmapped features of cancer transcriptomes, linked to disease progression and immune evasion.

Of popsicles and crackers: when spatio-temporal memory is not integrated into children's decision-making.

Prior research has used innovative paradigms to show that some non-human animal species demonstrate behavioural choices (i.e. foraging for a food item at a specific location, and at a time that guarantees it has not yet decayed), reflecting episodic-like or 'WWW' memory (memory for 'what' happened, 'where' and 'when'). These results raised the question of whether similar approaches could be used to examine memory in young children in order to reduce verbal demands. The present research examines the extent to which children's WWW memory aligns with memory-based choices in 3- to 5-year-olds (n = 95; study 1) and in 7- to 11-year-olds and adults (n = 168; study 2). Results indicate that preschoolers' struggle with choice-based tasks probably reflects difficulty integrating their WWW memory with an understanding that certain items decay over time. Moreover, a convergence between verbal recall measures and choice-based measures is observable in 7-year-olds and beyond, reflecting a stronger integration of memory signals, understanding of state transformation, and decision-making. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Close Range and High-Resolution Detection of Vibration by Ultrasonic Wave Using Silicon-on-Nothing PMUTs.

This article presents a novel method for close-range, high-resolution ultrasonic time-of-flight (ToF) ranging using piezoelectric micromachined ultrasonic transducers (PMUTs) operating below the device resonance in air. The proposed method involves cross correlation techniques to accurately detect the reflected echo signals despite the presence of ringdown signal interference. For the experiments, a high fill-factor array of silicon-on-nothing (SON) PMUTs was used to enhance the signal-to-noise ratio (SNR). A thorough investigation was conducted to determine the optimal driving frequency for below-resonance ToF ranging, to improve resolution and minimize detection errors. The results of the experiments showed that the system was able to accurately measure sub- µ m vibrations of a metal plate placed 13 mm away from the PMUT array. The system exhibited the ability to detect target object vibrations with a peak-to-peak displacement under 6 µ m and sub- µ m floor noise. Moreover, the maximum detectable vibration frequency reached up to 1 kHz. This study highlights the potential of the proposed ToF ranging method in noncontact vibration monitoring applications across various fields, such as robotics and predictive maintenance.

Localized Evaporative Cooling Explains Observed Ocular Surface-Temperature Patterns.

Purpose: We determined interblink corneal surface-temperature decline and tear-film evaporation rates of localized tear breakup cold regions (LCRs) and localized tear unbroken warm regions (LWRs) of the corneal surface, as well as that of the overall average corneal surface. Methods: Each subject underwent 4 inter-day visits where the interblink corneal surface-temperature history of the right eye was measured using a FLIR A655sc infrared thermographer. Corneal surface temperature history was analyzed to determine the overall, LCR, and LWR temperature-decline rates. Evaporation rates of LCR and LWR regions were determined from the measured LCR and LWR temperature data using the physical model of Dursch et al. Results: Twenty subjects completed the study. Mean (SD) difference of LCR temperature-decline rate was -0.08 (0.07)°C/s faster than LWR (P < 0.0001). Similarly, evaporation rates of LCR and LWR were statistically different (P < 0.0001). At ambient temperature, mean LCR and LWR evaporation rates were 76% and 27% of pure water evaporation flux, respectively. There was no statistically significant difference between the inter-day measured temperature-decline rates and the interblink starting temperature. Conclusions: Significant differences in corneal temperature-decline rate and evaporation rate between LCR and LWR were quantified using infrared thermography. In agreement with literature, LCRs and LWRs correlate directly with fluorescein break-up areas and unbroken tear areas, respectively. Because lipid-evaporation protection is diminished in breakup areas, higher local evaporation rates and faster local cooling rates occur in LCRs relative to LWRs. Our results confirm this phenomenon clinically for the first time.

Dissemination of health content through social networks: YouTube and opioid use disorders.

INTRODUCTION: Most Americans now access social media platforms, including YouTube, to obtain health information. However, few studies have evaluated the quality of YouTube content related to opioid use disorder (OUD), including medications for OUD (MOUD; buprenorphine) and harm reduction resources (e.g., naloxone). The purpose of this cross-sectional analysis was to assess the quality, accuracy, and reliability of MOUD and harm reduction-related video content available on YouTube. METHODS: The study team conducted a YouTube search between June 2022 and July 2022 using key words related to MOUD and harm reduction content (e.g., "suboxone," "methadone," "Narcan"). The 5 most viewed videos from each search term were analyzed for quality (i.e., Global Quality Scale; GQS), accuracy (i.e., JAMA Benchmark Criteria), and reliability (i.e., DISCERN). Videos that were non-English, duplicate, or that did not directly mention OUD, MOUD, or harm reduction were excluded from the review (N = 6). RESULTS: YouTube videos (N = 70) were mostly produced by medical professionals (27.1 %), independent nonmedical users (21.4 %; e.g., vloggers, individuals documenting their experiences), medical organizations (17.1 %; e.g., hospitals, treatment programs), and/or media (14.3 %; e.g., news agencies). The target audience was primarily the general public (65.7 %), people who use opioids (20.0 %), and healthcare providers (10.0 %). Videos containing MOUD content (N = 64, 61.4 %) mostly focused on suboxone (25.0 %), methadone (23.4 %), Sublocade (14.1 %), and subutex/buprenorphine (14.1 %). The median quality score was 2 based on the GQS with 3 videos receiving the highest quality rating (5). Two videos were highly rated for accuracy per all three JAMA Benchmark criteria. Videos produced by nonmedical educational channels had the highest overall reliability scores on the DISCERN criteria (median 4), followed by medical professionals (median 3), and medical organizations (median 2.5). CONCLUSION: The overall quality, accuracy, and reliability of MOUD and harm reduction related content posted on YouTube is poor. The lack of evidence-based content posted on YouTube reinforces the need for public health expert involvement in disseminating guideline-based content on social media.

Provider and administrator attitudes and experiences with implementing telebuprenorphine during the COVID-19 pandemic: a mixed-methods survey.

Introduction: This mixed-methods study assessed buprenorphine provider and administrator perceptions and experiences in offering telebuprenorphine during the COVID-19 pandemic. Methods: Semi-structured interviews were conducted between June 2021 and September 2021 among telebuprenorphine providers and administrators (N=16) and assessed for program design and implementation strategies, clinical workflow, patient-level factors influencing program entry and retention, and challenges and solutions to improving clinical care. Results: Clinician (n=15) and administrator (n=1) participants identified changes to clinical workflow, including increased administrative tasks to confirm patient receipt of prescribed medications, completion of referrals to community- or specialty treatment, and locating available pharmacies and laboratory services. Challenges consisted of staff redeployment to COVID-19 related responsibilities, prior authorization requirements for buprenorphine prescriptions, billing structures that under-reimbursed for telephone or video visits, and concerns with changes in government regulations. Strategies to improving telebuprenorphine included offering "hotlines" to facilitate same-day visits, expanding between-visit support, establishing workflows with community pharmacies to ensure seamless dispensing of buprenorphine, co-location of behavioral health providers, and distributing donated mobile phones to patients. Suggested technologies for enhancing care included text messaging (75%) and smartphone applications (56.3%). Conclusions: Findings from this study highlight considerable heterogeneity in the delivery of telebuprenorphine services.

Alterations in circulating measures of Th2 immune responses pre-lung transplant associates with reduced primary graft dysfunction.

Primary graft dysfunction (PGD) is a complication of lung transplantation that continues to cause significant morbidity. The Th2 immune response has been shown to counteract tissue-damaging inflammation. We hypothesized that Th2 cytokines/chemokines in blood would be associated with protection from PGD. Utilizing pretransplant sera from the multicenter clinical trials in organ transplantation study, we evaluated Th2 cytokines/chemokines in 211 patients. Increased concentrations of Th2 cytokines were associated with freedom from PGD, namely IL-4 (odds ratio [OR] 0.66 [95% confidence interval {CI} 0.45-0.99], p = 0.043), IL-9 (OR 0.68 [95% CI 0.49-0.94], p = 0.019), IL-13 (OR 0.73 [95% CI 0.55-0.96], p = 0.023), and IL-6 (OR 0.74 [95% CI 0.56-0.98], p = 0.036). Multivariable regression performed for each cytokine, including clinically relevant covariables, confirmed these associations and additionally demonstrated association with IL-5 (OR 0.57 [95% CI 0.36-0.89], p = 0.014) and IL-10 (OR 0.55 [95% CI 0.32-0.96], p = 0.035). Higher levels of Th2 immune response before lung transplant appear to have a protective effect against PGD, which parallels the Th2 role in resolving inflammation and tissue injury. Pretransplant cytokine assessments could be utilized for recipient risk stratification.

The utilisation of teledentistry in Australia: A systematic review and meta-analysis.

BACKGROUND: Teledentistry is the usage of information-based technologies to deliver healthcare services remotely. It is used to deliver care in regional, rural and remote regions and was particularly useful to deliver care during the COVID-19 pandemic. OBJECTIVE: This systematic review and meta-analysis aimed to determine teledentistry utilisation in Australia. METHODS: The databases PubMed, Google Scholar, EMBASE and Web of Science were searched from inception to June-2024. The phrases "Dental" AND "Telehealth" AND "Australia" and "Teledentistry" AND "Australia" were used. Two authors completed the study selection and data extraction. The Joanna Briggs Institute Critical Appraisal Tools were used to assess quality and bias. RESULTS: Eighteen articles met the inclusion criteria. There were six diagnostic tests, six cross-sectional studies, 4 economic evaluations, one qualitative study and one expert opinion. Teledentistry was accurate for screening caries (average sensitivity=69.7 %, average specificity=97.4 %). There also appeared to be a non-significant negative correlation between specificity and sensitivity (r = 0.432). Opinions regarding teledentistry were mixed from clinicians but positive from patients. Teledentistry may also lead to savings for patients and healthcare providers. CONCLUSION: Teledentistry increases healthcare access especially for people in regional, rural and remote areas. It is an effective screening tool for caries. Whilst the opinions of clinicians were mixed, potential implementation barriers were identified which could improve opinions of clinicians and increase implementation. CLINICAL IMPORTANCE: This study demonstrates teledentistry as a satisfactory tool for screening caries. This could be beneficial to those with difficulties visiting dentists in-person, particularly if they live in regional, rural or remote areas.

Fentanyl Test Strips for Harm Reduction: A Scoping Review.

BACKGROUND: High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized. METHODS: A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template. RESULTS: A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention. CONCLUSIONS: Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary.

Transitions of care between jail-based medications for opioid use disorder and ongoing treatment in the community: A retrospective cohort study.

BACKGROUND: Offering medications for opioid use disorder (MOUD) in carceral settings significantly reduces overdose. However, it is unknown to what extent individuals in jails continue MOUD once they leave incarceration. We aimed to assess the relationship between in-jail MOUD and MOUD continuity in the month following release. METHODS: We conducted a retrospective cohort study of linked NYC jail-based electronic health records and community Medicaid OUD treatment claims for individuals with OUD discharged from jail between 2011 and 2017. We compared receipt of MOUD within 30 days of release, among those with and without MOUD at release from jail. We tested for effect modification based on MOUD receipt prior to incarceration and assessed factors associated with treatment discontinuation. RESULTS: Of 28,298 eligible incarcerations, 52.8 % received MOUD at release. 30 % of incarcerations with MOUD at release received community-based MOUD within 30 days, compared to 7 % of incarcerations without MOUD (Risk Ratio: 2.62 (2.44-2.82)). Most (69 %) with MOUD claims prior to incarceration who received in-jail MOUD continued treatment in the community, compared to 9 % of those without prior MOUD. Those who received methadone (vs. buprenorphine), were younger, Non-Hispanic Black and with no history of MOUD were less likely to continue MOUD following release. CONCLUSIONS: MOUD maintenance in jail is strongly associated with MOUD continuity upon release. Still, findings highlight a gap in treatment continuity upon-reentry, especially among those who initiate MOUD in jail. In the wake of worsening overdose deaths and troubling disparities, improving MOUD continuity among this population remains an urgent priority.

Assessing the impact of jail-initiated medication for opioid use disorder: A multisite analysis of the SOMATICS collaborative.

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.

Biphasic burrowing in Atlantic hagfish (Myxine limosa).

Myxine limosa is a burrowing species of hagfish that occurs in the western North Atlantic in areas with muddy substrate and at depths generally greater than 100 meters. Burrowing of M. limosa has been observed from submersibles, but little is known about the behavior of these animals within the substrate or the biomechanical mechanisms involved. Here, we investigated burrowing in M. limosa by observing individuals as they burrowed through transparent gelatin. A photoelastic setup using crossed polarizers allowed us to visualize stress development in the gelatin as the hagfish moved through it. We found that M. limosa created U-shaped burrows in gelatin using a stereotyped, two-phase burrowing behavior. In the first ('thrash') phase, hagfish drove their head and their anterior body into the substrate using vigorous sinusoidal swimming movements, with their head moving side-to-side. In the second ('wriggle') phase, swimming movements ceased, with propulsion coming exclusively from the anterior, submerged portion of body. The wriggle phase involved side-to-side head movements and movements of the submerged part of the body that resembled the internal concertina strategy used by caecilians and uropeltid snakes. The entire burrowing process took on average 7.6 min to complete and ended with the hagfish's head protruding from the substrate and the rest of its body generally concealed. Understanding the burrowing activities of hagfishes could lead to improved understanding of sediment turnover in marine benthic habitats, new insights into the reproductive behavior of hagfishes, or even inspiration for the design of burrowing robots.