Morphology of the unique egg cases of hornsharks (Heterodontiformes: Heterodontidae).

Many of the egg cases of oviparous chondrichthyans remain unknown and undescribed in the literature. Egg cases can be a useful taxonomic character for species distinction and can be a valuable indicator of a species distribution in the field. In this study, the egg cases for 9 of the 10 nominal species of Heterodontus are described and compared, and the terminology and methodology for studying them are standardized. Heterodontus egg cases are distinct and easily identifiable from other oviparous egg cases by having a unique corkscrew shape formed by a pair of lateral keels spiraling along its length. Heterodontus egg cases range between 7.5 and 14.5 cm in egg case length, 3.7 and 5.8 cm in egg case width at midportion, and have 0.75-4 complete rotations. Morphometric measurements of egg cases from the nine species were subjected to multivariate analysis, with unique characters enabling distinction between them. Egg cases can be separated into three morphotypes: the "wide keels lacking tendrils" group, the "narrow keels with tendrils" group, and the "wide keels with tendrils" group. The egg case of Heterodontus ramalheira remains unknown.

Reallocation of the magnificent catshark Proscyllium magnificum Last & Vongpanich, 2004 to the genus Ctenacis Compagno, 1973 (Carcharhiniformes: Proscylliidae).

The magnificent catshark Proscyllium magnificum was described in 2004 based off five specimens collected in the Andaman Sea off Myanmar. It was originally allocated to the genus Proscyllium, but recent molecular analyses suggested it was more closely related to the harlequin catshark Ctenacis fehlmanni from the western Indian Ocean. This study incorporated meristics and external and internal morphology, together with molecular data to reclassify the magnificent catshark as Ctenacis magnificum and provides revised diagnoses for the genera Ctenacis and Proscyllium. Ctenacis consists of two allopatric Indian Ocean species, while Proscyllium is monotypic genus confined to the northwest Pacific. The revised Ctenacis can be distinguished from Proscyllium in having a broader and longer head (head length 21%-23% vs. 16%-18% of total length), distance between pectoral and pelvic bases shorter than head length (vs. greater than head length), more teeth (upper jaw with 80-86 vs. 46-62 tooth files), and a complex colour pattern of dark reddish-brown blotches and saddles (vs. colour pattern of small black spots). A revised key to the genera of proscylliids and species of Ctenacis is provided.

Oxygen exposure decreases the yield of high-molecular-weight DNA from some anaerobic bacteria and bacterial communities during DNA extraction.

OBJECTIVES: The central challenge in third-generation sequencing lies in meeting the requirements for DNA quality (integrity and purity) and quantity. Therefore, novel improvements in DNA extraction methods are needed to satisfy these requirements. We reasoned that in anaerobic microbial communities, the presence of certain strict anaerobes containing oxygen-activated DNase activity might contribute substantially to the poor integrity of extracted metagenomic DNA (or genomic DNA from some pure cultures) if exposed to air. METHODS: To test this hypothesis, we developed an enhanced genomic and metagenomic DNA isolation technique that we applied to a specifically chosen set of both strict and aerotolerant anaerobes, as well as to the hindgut microbiota of a herbivorous marine fish. RESULTS: Considering the quality (or degradation) of extracted DNA obtained under anaerobic versus aerobic conditions, we found that DNA extracted aerobically from cells of some strict anaerobes showed more degradation of high molecular weight DNA than analogous preparations under anaerobic conditions. In contrast, with the selected aerotolerant anaerobes, no discernible difference was found between the molecular sizes of DNA extracted aerobically and anaerobically. Metagenomic DNA extracted from the fish hindgut microbiota showed higher yields and better quality under anaerobic conditions compared to aerobic conditions. CONCLUSION: Our study effectively demonstrates the advantages of our improved extraction protocol in anaerobic conditions. This is evident through the improved quality of extracted DNA. Such findings may be valuable for studies, especially metagenomic studies, where the quality and quantity of DNA are crucial for downstream analysis.

Identification of Human Pathways Acting on Nuclear Non-Coding RNAs Using the Mirror Forward Genetic Approach.

Despite critical roles in diseases, human pathways acting on strictly nuclear non-coding RNAs have been refractory to forward genetics. To enable their forward genetic discovery, we developed a single-cell approach that "Mirrors" activities of nuclear pathways with cytoplasmic fluorescence. Application of Mirror to two nuclear pathways targeting MALAT1's 3' end, the pathway of its maturation and the other, the degradation pathway blocked by the triple-helical Element for Nuclear Expression (ENE), identified nearly all components of three complexes: Ribonuclease P and the RNA Exosome, including nuclear DIS3, EXOSC10, and C1D, as well as the Nuclear Exosome Targeting (NEXT) complex. Additionally, Mirror identified DEAD-box helicase DDX59 associated with the genetic disorder Oral-Facial-Digital syndrome (OFD), yet lacking known substrates or roles in nuclear RNA degradation. Knockout of DDX59 exhibits stabilization of the full-length MALAT1 with a stability-compromised ENE and increases levels of such long non-coding RNAs as NEAT1_1 and NIPBL-DT, as well as 3'-extended forms of small nuclear RNAs. It also exhibits extensive retention of minor introns, including in OFD-associated genes, suggesting a mechanism for DDX59 association with OFD. Mirror efficiently identifies pathways acting on strictly nuclear non-coding RNAs, including essential and indirectly-acting components, and, as a result, uncovers unexpected links to human disease.

Increased Risk of New-Onset Hypertension in Patients With Narcolepsy Initiating Sodium Oxybate: A Real-World Study.

OBJECTIVE: To compare intermediate-term risk of new-onset hypertension between normotensive patients with narcolepsy initiating sodium oxybate (SXB cohort) and those not initiating sodium oxybate (control cohort). PATIENTS AND METHODS: This retrospective cohort study used MarketScan administrative claims data from January 1, 2014, to February 29, 2020. Eligible patients were 18 years of age or older with continuous enrollment (≥180 days before and after cohort entry), had one or more narcolepsy claims or a prescription fill for sodium oxybate, had no history of hypertension or antihypertensive medication use, and had no use of sodium oxybate within 13 months before cohort entry. Patients in the SXB and control cohorts were matched 1:2 for the propensity score to balance baseline characteristics. End points were (1) a composite of new-onset hypertension diagnosis or antihypertensive medication initiation and (2) new-onset hypertension diagnosis. Patients were monitored for 180 days, until outcome occurrence, sodium oxybate discontinuation (SXB cohort), or sodium oxybate initiation (control cohort). Risk per 100 patients was reported; differences were evaluated using logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The SXB and control cohorts included 954 and 1908 patients, respectively. Risk of new-onset hypertension diagnosis or antihypertensive medication initiation was higher in the SXB cohort than in the control cohort (6.60 vs 4.20 per 100 patients; OR, 1.61; 95% CI, 1.15 to 2.27). Risk of a new-onset hypertension diagnosis only in the SXB cohort was 0.94 per 100 patients and 0.52 per 100 patients in the control cohort (OR, 1.81; 95% CI, 0.73 to 4.46). CONCLUSION: In this study, sodium oxybate use was associated with a new-onset hypertension diagnosis or antihypertensive medication initiation in normotensive patients with narcolepsy.

Evaluation of Pregabalin bioadhesive multilayered microemulsion IOP-lowering eye drops.

In spite of available treatment options, glaucoma continues to be a leading cause of irreversible blindness in the world. Current glaucoma medications have multiple limitations including: lack of sustained action; requirement for multiple dosing per day, ocular irritation and limited options for drugs with different mechanisms of action. Previously, we demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner. The current study was designed to evaluate pregabalin microemulsion eye drops and to estimate its efficacy in humans using in silico methods. Molecular docking studies of pregabalin against CACNA2D1 of mouse, rabbit, and human were performed. Pregabalin microemulsion eye drops were characterized using multiple in vivo studies and its stability was evaluated over one year at different storage conditions. Molecular docking analyses and QSPR of pregabalin confirmed its suitability as a new IOP-lowering medication that functions using a new mechanism of action by binding to CACNA2D1 in all species evaluated. Because of its prolonged corneal residence time and corneal penetration enhancement, a single topical application of pregabalin ME can provide an extended IOP reduction of more than day in different animal models. Repeated daily dosing for 2 months confirms the lack of any tachyphylactic effect, which is a common drawback among marketed IOP-lowering medications. In addition, pregabalin microemulsion demonstrated good physical stability for one year, and chemical stability for 3-6 months if stored below 25 °C. Collectively, these outcomes greatly support the use of pregabalin eye drops as once daily IOP-lowering therapy for glaucoma management.

Modeling Recovery Housing Retention and Program Outcomes by Justice Involvement among Residents in Virginia, USA: An Observational Study.

Living in recovery housing can improve addiction recovery and desistance outcomes. This study examined whether retention in recovery housing and types of discharge outcomes (completed, "neutral," and "negative" outcomes) differed for clients with recent criminal legal system (CLS) involvement. Using data from 101 recovery residences certified by the Virginia Association of Recovery Residences based on 1,978 individuals completing the REC-CAP assessment, competing risk analyses (cumulative incidence function, restricted mean survival time, and restricted mean time lost) followed by the marginalization of effects were implemented to examine program outcomes at final discharge. Residents with recent CLS involvement were more likely to be discharged for positive reasons (successful completion of their goals) and premature/negative reasons (e.g., disciplinary releases) than for neutral reasons. Findings indicate that retention for 6-18 months is essential to establish and maintain positive discharge outcomes, and interventions should be developed to enhance retention in recovery residents with recent justice involvement.

Sexual and gender minority content in undergraduate medical education in the United States and Canada: current state and changes since 2011.

PURPOSE: To characterize current lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI +) health-related undergraduate medical education (UME) curricular content and associated changes since a 2011 study and to determine the frequency and extent of institutional instruction in 17 LGBTQI + health-related topics, strategies for increasing LGBTQI + health-related content, and faculty development opportunities. METHOD: Deans of medical education (or equivalent) at 214 allopathic or osteopathic medical schools in Canada and the United States were invited to complete a 36-question, Web-based questionnaire between June 2021 and September 2022. The main outcome measured was reported hours of LGBTQI + health-related curricular content. RESULTS: Of 214 schools, 100 (46.7%) responded, of which 85 (85.0%) fully completed the questionnaire. Compared to 5 median hours dedicated to LGBTQI + health-related in a 2011 study, the 2022 median reported time was 11 h (interquartile range [IQR], 6-16 h, p < 0.0001). Two UME institutions (2.4%; 95% CI, 0.0%-5.8%) reported 0 h during the pre-clerkship phase; 21 institutions (24.7%; CI, 15.5%-33.9%) reported 0 h during the clerkship phase; and 1 institution (1.2%; CI, 0%-3.5%) reported 0 h across the curriculum. Median US allopathic clerkship hours were significantly different from US osteopathic clerkship hours (4 h [IQR, 1-6 h] versus 0 h [IQR, 0-0 h]; p = 0.01). Suggested strategies to increase content included more curricular material focusing on LGBTQI + health and health disparities at 55 schools (64.7%; CI, 54.6%-74.9%), more faculty willing and able to teach LGBTQI + -related content at 49 schools (57.7%; CI, 47.1%-68.2%), and more evidence-based research on LGBTQI + health and health disparities at 24 schools (28.2%; CI, 18.7%-37.8%). CONCLUSION: Compared to a 2011 study, the median reported time dedicated to LGBTQI + health-related topics in 2022 increased across US and Canadian UME institutions, but the breadth, efficacy, or quality of instruction continued to vary substantially. Despite the increased hours, this still falls short of the number of hours based on recommended LGBTQI + health competencies from the Association of American Medical Colleges. While most deans of medical education reported their institutions' coverage of LGBTQI + health as 'fair,' 'good,' or 'very good,' there continues to be a call from UME leadership to increase curricular content. This requires dedicated training for faculty and students.

Internet-based, continuously available Narcotics Anonymous meetings: a new resource for access to Twelve Step support for abstinence.

Background: A Zoom-based website was developed in 2020 that offers continuous access to online Narcotics Anonymous (NA) meetings for the first time. This website provides immediate access for persons with substance use disorder to support abstinence from substance-related addictive disorders.Objectives: This study is designed to characterize attendees employing this online format; to evaluate their experiences for gaining support to maintain abstinence; and to compare the 24/7 experience to face-to-face (FF) meetings they attend.Methods: An anonymous 33-item survey was made available on the 24/7 NA website that links to the 24/7 meetings. Persons accessing the site could choose to fill out the survey.Results: 530 respondents completed the survey (64.9% female/35.1% male). Most had stable prior involvement in NA. They had attended more 24/7 meetings (14.9, SD 19.7) than FF meetings (4.6, SD 7.8) in the previous month. 86% had previously attended FF meetings, 48% had served as sponsors, and 92% reported that the 24/7 meetings were more comfortable for them than the FF meetings (p < .001, Cohen's d = 0.65) and more supportive of abstinence (p < .001, Cohen's d = 0.91). Of the respondents, 8% were still using drugs, of whom 52% had previously completed some of the Twelve Steps.Conclusions: The 24/7 format provides a new and easily accessible way for NA members to gain support for abstinence and is positively rated by attendees seeking support for recovery from substance use disorders. It may serve as a valuable adjunct to the traditional FF format.

Hydrodynamic Mechanism for Clumping along the Equatorial Rings of SN1987A and Other Stars.

An explanation for the origin and number of clumps along the equatorial ring of Supernova 1987A has eluded decades of research. Our linear analysis and hydrodynamic simulations of the expanding ring prior to the supernova reveal that it is subject to the Crow instability between vortex cores. The dominant wave number is remarkably consistent with the number of clumps, suggesting that the Crow instability stimulates clump formation. Although the present analysis focuses on linear fluid flow, future nonlinear analysis and the incorporation of additional stellar physics may further elucidate the remnant structure and the evolution of the progenitor and other stars.

Investigating the dissociative subtype of post-traumatic stress disorder in single- and multi-event trauma-exposed youth: Prevalence, course, prognosis, severity and functional impairment.

OBJECTIVES: This study aimed, following both single- and multi-event trauma, to ascertain prevalence and course of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in youth; how well early PTSD-DS predicts later PTSD; and whether dissociation accounts for unique variance in post-traumatic stress symptoms (PTSS) and functional impairment over and above the effect of other post-trauma cognitive processing factors and PTSS respectively. DESIGN AND METHODS: This study is a secondary analysis of data from the Acute Stress Programme for Children and Teenagers study (n = 234) and the Coping in Care After Trauma study (n = 110) in which children had experienced single- and multi-event trauma respectively. RESULTS: PTSD-DS diagnosis was common in children with PTSD regardless of trauma experienced (>39.0%). PTSD-DS showed a similar trajectory of natural recovery to PTSD, and it was similarly predictive of later PTSD following single-event trauma. Finally, dissociation was a significant factor in PTSS and functional impairment. CONCLUSIONS: These results should be viewed in the context of several limitations including narrow sample of participants which reduces the generalizability of results, concerns around children's ability to conceptualize challenging concepts such as dissociation and the use of self-report measures to form diagnostic groups. The PTSD-DS diagnosis may offer clinical utility to the extant PTSD diagnosis in children and adolescents, as dissociation has been shown to be a contributory factor in the maintenance of both PTSS and functional impairment. Further research is required to inform further editions of the DSM and other diagnostic systems.

Proof of concept for quantitative adverse outcome pathway modeling of chronic toxicity in repeated exposure.

Adverse Outcome Pathway (AOP) is a useful tool to glean mode of action (MOE) of a chemical. However, in order to use it for the purpose of risk assessment, an AOP needs to be quantified using in vitro or in vivo data. Majority of quantitative AOPs developed so far, were for single exposure to progressively higher doses. Limited attempts were made to include time in the modeling. Here as a proof-of concept, we developed a hypothetical AOP, and quantified it using a virtual dataset for six repeated exposures using a Bayesian Network Analysis (BN) framework. The virtual data was generated using realistic assumptions. Effects of each exposure were analyzed separately using a static BN model and analyzed in combination using a dynamic BN (DBN) model. Our work shows that the DBN model can be used to calculate the probability of adverse outcome when other upstream KEs were observed earlier. These probabilities can help in identification of early indicators of AO. In addition, we also developed a data driven AOP pruning technique using a lasso-based subset selection, and show that the causal structure of AOP is itself dynamic and changes over time. This proof-of-concept study revealed the possibility for expanding the applicability of the AOP framework to incorporate biological dynamism in toxicity appearance by repeated insults.

First observation of a skate egg case nursery in the Ross Sea.

Areas of importance to Southern Ocean skates are poorly defined. Here, we identify a deepwater skate egg case nursery in a discrete location at ~460 m depth off Cape Adare in the Southern Ocean. This is the first confirmed observation of a skate nursery area in the Ross Sea and only the second observation for the Southern Ocean. The morphology and size of the egg cases were consistent with the genus Bathyraja and most likely belong to the Bathyraja sp. (cf. eatonii). The nursery occurs within the "no take" General Protection Zone of the Ross Sea region marine protected area, where commercial fishing is prohibited.

Sharks checking in to the sponge hotel: First internal use of sponges of the genus Agelas and family Irciniidae by banded sand catsharks Atelomycterus fasciatus.

Trawl surveys within and surrounding two northwestern Australian marine parks revealed banded sand catsharks Atelomycterus fasciatus (family Atelomycteridae) taking refuge within large sponges of the family Irciniidae (Demospongiae: Dictyoceratida) and the genus Agelas (Demospongiae: Agelasida: Agelasidae). Five sponges contained a total of 57 A. fasciatus, comprising both sexes and both immature and mature individuals ranging from 102 to 390 mm total length (TL). In the same surveys, only five A. fasciatus were captured unassociated with sponges, suggesting that sponges are an important microhabitat for A. fasciatus and may provide a daytime refuge from predators. A southerly range extension is also reported for this species.

Assessing a pilot scheme of intensive support and assertive linkage in levels of engagement, retention, and recovery capital for people in recovery housing using quasi-experimental methods.

INTRODUCTION: Strong and ever-growing evidence highlights the effectiveness of recovery housing in supporting and sustaining substance use disorder (SUD) recovery, especially when augmented by intensive support that includes assertive linkages to community services. This study aims to evaluate a pilot intensive recovery support (IRS) intervention for individuals (n = 175) entering certified Level II and III recovery residences. These individuals met at least three out of five conditions (no health insurance; no driving license; substance use in the last 14 days; current unemployment; possession of less than $75 capital). The study assesses the impact of the IRS on engagement, retention, and changes in recovery capital, compared to the business-as-usual Standard Recovery Support (SRS) approach (n = 1758). METHODS: The study employed quasi-experimental techniques to create weighted and balanced counterfactual groups. These groups, derived from the Recovery Capital assessment tool (REC-CAP), enabled comparison of outcomes between people receiving IRS and those undergoing SRS. RESULTS: After reweighting for resident demographics, service needs, and barriers to recovery, those receiving IRS exhibited improved retention rates, reduced likelihood of disengagement, and growth in recovery capital after living in the residence for 6-9 months. CONCLUSION: The results from this pilot intervention indicate that intensive recovery support, which integrates assertive community linkages and enhanced recovery coaching, outperforms a balanced counterfactual group in engagement, length of stay, and recovery capital growth. We suggest that this model may be particularly beneficial to those entering Level II and Level III recovery housing with lower levels of recovery capital at admission.

Antigen perception in T cells by long-term Erk and NFAT signaling dynamics.

Immune system threat detection hinges on T cells' ability to perceive varying peptide-major histocompatibility complex (pMHC) antigens. As the Erk and NFAT pathways link T cell receptor engagement to gene regulation, their signaling dynamics may convey information about pMHC inputs. To test this idea, we developed a dual reporter mouse strain and a quantitative imaging assay that, together, enable simultaneous monitoring of Erk and NFAT dynamics in live T cells over day-long timescales as they respond to varying pMHC inputs. Both pathways initially activate uniformly across various pMHC inputs but diverge only over longer (9+ h) timescales, enabling independent encoding of pMHC affinity and dose. These late signaling dynamics are decoded via multiple temporal and combinatorial mechanisms to generate pMHC-specific transcriptional responses. Our findings underscore the importance of long timescale signaling dynamics in antigen perception and establish a framework for understanding T cell responses under diverse contexts.

Pathophysiological Sex Differences in Heart Failure Progression After Acute Coronary Syndrome: Insights From the EXAMINE Trial.

BACKGROUND: Therapies can reduce the risk of heart failure (HF) development and progression in type 2 diabetes; nevertheless, the risk of these outcomes is greater in females than in males. METHODS AND RESULTS: To investigate sex differences in HF development and progression, we compared baseline circulating proteins (Olink Cardiovascular II panel) in males and females with type 2 diabetes and recent acute coronary syndrome for the outcome of HF hospitalization. Data were from the placebo-controlled Examination of Cardiovascular Outcomes with Alogliptin vs Standard of Care (EXAMINE) trial. Pathophysiological sex-differences were interpreted with network and pathway over-representation analyses. The EXAMINE trial enrolled 5380 participants (32.1% females) with biomarker data available for 95.4% of individuals. Analyses revealed 43 biomarkers were differentially expressed in HF hospitalization, of which 18 were sex specific. Among these 43 biomarkers, interleukin-6 was identified as a central node for the pathogenesis of HF hospitalization in both females and in males. Additional pathway over-representation analyses demonstrated that biomarkers associated with inflammatory pathways related to endothelial dysfunction and cardiac fibrosis were more up-regulated in females than males with HF hospitalization. Differential expression of 3 biomarkers (pentraxin-related protein 3, hydroxyacid oxidase 1, and carbonic anhydrase 5A) was independently associated with an increased risk of HF hospitalization in females but not in males (interaction P < .05). CONCLUSIONS: In males and females with type 2 diabetes and acute coronary syndrome, interleukin-6 seems to be central in the pathogenesis of HF. Females exhibit higher levels of circulating proteins related to immunological pathways, reflecting sex-specific differences underlying HF development and progression.

Chakrabartyella piscis gen. nov., sp. nov., a member of the family Lachnospiraceae, isolated from the hindgut of the marine herbivorous fish Kyphosus sydneyanus.

A Gram-stain-negative, non-spore-forming, rod-shaped, obligately anaerobic bacterium, designated strain BP5GT, was isolated from the hindgut of a silver drummer (Kyphosus sydneyanus) fish collected from the Hauraki Gulf, New Zealand. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the isolate belonged to the family Lachnospiraceae in the phylum Bacillota and was most closely related to Anaerotignum propionicum with 94.06 % sequence identity. Isolate BP5GT grew on agar medium containing mannitol and fish gut fluid as carbon sources. Clear colonies of approximately 1 mm diameter of the isolate grew within a week at 20-28 °C (optimum, 28 °C) and pH 7.6-8.5 (optimum, pH 8.5). Strain BP5GT was very sensitive to NaCl and the optimal concentration for growth was 0.045 % (w/v). Acetate and propionate were the major fermentation products. The major cellular fatty acids were C12 : 0, C14 : 0, C15 : 0 and C16 : 0. The genome sequence of the isolate was determined. Its G+C content was 38.41 mol% and the 71.41 % average nucleotide identity of the BP5GT genome to its closest neighbour with a sequenced genome (A. propionicum DSM 1682T) indicated low genomic relatedness. Based on the phenotypic and taxonomic characteristics observed in this study, a novel genus and species named Chakrabartyella piscis gen. nov., sp. nov. is proposed for isolate BP5GT (=ICMP 24687T=JCM 35769T).