A median fin derived from the lateral plate mesoderm and the origin of paired fins.

The development of paired appendages was a key innovation during evolution and facilitated the aquatic to terrestrial transition of vertebrates. Largely derived from the lateral plate mesoderm (LPM), one hypothesis for the evolution of paired fins invokes derivation from unpaired median fins via a pair of lateral fin folds located between pectoral and pelvic fin territories1. Whilst unpaired and paired fins exhibit similar structural and molecular characteristics, no definitive evidence exists for paired lateral fin folds in larvae or adults of any extant or extinct species. As unpaired fin core components are regarded as exclusively derived from paraxial mesoderm, any transition presumes both co-option of a fin developmental programme to the LPM and bilateral duplication2. Here, we identify that the larval zebrafish unpaired pre-anal fin fold (PAFF) is derived from the LPM and thus may represent a developmental intermediate between median and paired fins. We trace the contribution of LPM to the PAFF in both cyclostomes and gnathostomes, supporting the notion that this is an ancient trait of vertebrates. Finally, we observe that the PAFF can be bifurcated by increasing bone morphogenetic protein signalling, generating LPM-derived paired fin folds. Our work provides evidence that lateral fin folds may have existed as embryonic anlage for elaboration to paired fins.

Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

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.

The impact of paleoclimatic changes on body size evolution in marine fishes.

Body size is an important species trait, correlating with life span, fecundity, and other ecological factors. Over Earth's geological history, climate shifts have occurred, potentially shaping body size evolution in many clades. General rules attempting to summarize body size evolution include Bergmann's rule, which states that species reach larger sizes in cooler environments and smaller sizes in warmer environments, and Cope's rule, which poses that lineages tend to increase in size over evolutionary time. Tetraodontiform fishes (including pufferfishes, boxfishes, and ocean sunfishes) provide an extraordinary clade to test these rules in ectotherms owing to their exemplary fossil record and the great disparity in body size observed among extant and fossil species. We examined Bergmann's and Cope's rules in this group by combining phylogenomic data (1,103 exon loci from 185 extant species) with 210 anatomical characters coded from both fossil and extant species. We aggregated data layers on paleoclimate and body size from the species examined, and inferred a set of time-calibrated phylogenies using tip-dating approaches for downstream comparative analyses of body size evolution by implementing models that incorporate paleoclimatic information. We found strong support for a temperature-driven model in which increasing body size over time is correlated with decreasing oceanic temperatures. On average, extant tetraodontiforms are two to three times larger than their fossil counterparts, which otherwise evolved during periods of warmer ocean temperatures. These results provide strong support for both Bergmann's and Cope's rules, trends that are less studied in marine fishes compared to terrestrial vertebrates and marine invertebrates.

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.

Concordance and Discordance in the Phylogenomics of the Wrasses and Parrotfishes (Teleostei: Labridae).

Phylogenomic analysis of large genome-wide sequence data sets can resolve phylogenetic tree topologies for large species groups, help test the accuracy of and improve resolution for earlier multi-locus studies and reveal the level of agreement or concordance within partitions of the genome for various tree topologies. Here we used a target-capture approach to sequence 1088 single-copy exons for more than 200 labrid fishes together with more than 100 outgroup taxa to generate a new data-rich phylogeny for the family Labridae. Our time-calibrated phylogenetic analysis of exon-capture data pushes the root node age of the family Labridae back into the Cretaceous to about 79 Ma years ago. The monotypic Centrogenys vaigiensis, and the order Uranoscopiformes (stargazers) are identified as the sister lineages of Labridae. The phylogenetic relationships among major labrid subfamilies and within these clades were largely congruent with prior analyses of select mitochondrial and nuclear datasets. However, the position of the tribe Cirrhilabrini (fairy and flame wrasses) showed discordance, resolving either as the sister to a crown julidine clade or alternatively sister to a group formed by the labrines, cheilines and scarines. Exploration of this pattern using multiple approaches leads to slightly higher support for this latter hypothesis, highlighting the importance of genome-level data sets for resolving short internodes at key phylogenetic positions in a large, economically important groups of coral reef fishes. More broadly, we demonstrate how accounting for sources of biological variability from incomplete lineage sorting and exploring systematic error at conflicting nodes can aid in evaluating alternative phylogenetic hypotheses. [coral reefs; divergence time estimation; exon-capture; fossil calibration; incomplete lineage sorting.].

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.

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.

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.

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.

Sustained glucocorticoid tapering in the phase 3 trials of anifrolumab: a post hoc analysis of the TULIP-1 and TULIP-2 trials.

OBJECTIVES: Glucocorticoid sparing is a key priority for SLE management. We evaluated the effects of sustained glucocorticoid tapering in patients with SLE. MATERIAL AND METHODS: This was a post hoc analysis of the randomized, placebo-controlled, 52-week phase 3 Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-1 and TULIP-2 trials of anifrolumab (300 mg i.v. once every 4 weeks for 48 weeks) plus standard therapy in patients with moderate to severe SLE. In a cohort of patients receiving glucocorticoids (prednisone or equivalent) 10 mg or more per day at baseline, we assessed changes in glucocorticoid dosage, patient-reported outcomes (PROs) and safety. Outcome measures were compared between sustained glucocorticoid taper responders (7.5 mg or less per day by week 40 sustained through week 52) and non-responders, regardless of treatment group, and between patients receiving anifrolumab or placebo. RESULTS: Among the 726 patients in the TULIP trials, 375 patients received glucocorticoids 10 mg or more per day at baseline, and of these, 155 (41%) patients were sustained glucocorticoid taper responders. Compared with non-responders (n = 220), sustained glucocorticoid taper responders reduced their mean cumulative glucocorticoid dose by 32%, improved PRO scores, reduced blood pressure and experienced fewer serious adverse events. Sustained glucocorticoid tapering was achieved by 51% (96/190) of patients receiving anifrolumab vs 32% (59/185) receiving placebo. Compared with placebo, more anifrolumab-treated patients achieved both sustained glucocorticoid taper and reduced overall disease activity [38% (72/190) vs 23% (43/185)]. CONCLUSIONS: Sustained glucocorticoid tapering is associated with clinical benefits. Anifrolumab treatment has potential to reduce disease activity and glucocorticoid exposure, a key goal of SLE management. STUDY REGISTRATION: ClinicalTrials.gov identifier: NCT02446912 and NCT02446899.

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).

External validation and extension of the TIMI risk score for heart failure in diabetes for patients with recent acute coronary syndrome: An analysis of the EXAMINE trial.

AIMS: The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure (HF) in Diabetes (TRS-HFDM ) prognosticates HF hospitalization in people with type 2 diabetes (T2D). This study aimed to externally validate and extend its use for those with recent acute coronary syndrome (ACS). MATERIALS AND METHODS: The TRS-HFDM was externally validated in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial (n = 5380) and extended with natriuretic biomarkers. Missing data were multiply imputed. Initial TRS-HFDM variables were previous HF (2 points), atrial fibrillation (1 point), coronary artery disease (1 point), estimated glomerular filtration rate <60 ml/min/1.73 m2 (1 point), and urine albumin-to-creatinine ratio 30-300 mg/g (1 point) and >300 mg/g (2 points). RESULTS: In total, HF hospitalization occurred in 193 (3.6%) patients. Based on the TRS-HFDM , 25% of patients were classified as intermediate risk (1 point), 30% were classified as high risk (2 points), 19% were classified as very-high risk (3 points) and 26% were classified as severe risk (≥4 points). Before model extension, discrimination (C-index 0.76, 95%·CI 0.73-0.80) and calibration (calibration slope 0.82, 95%·CI 0.65-1.0; calibration-in-the-large -0.15, 95%·CI -0.37-0.64) were moderate-to-good in individuals with T2D and recent ACS. The extension of TRS-HFDM with the addition of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) improved discrimination (C-index 0.82, 95%·CI 0.79-0.85) and calibration (calibration slope 0.84, 95%·CI 0.66-1.02; calibration-in-the-large -0.12, 95%·CI -0.33-0.081) for this higher-risk population. CONCLUSION: The TRS-HFDM with the extension of NT-ProBNP improves risk stratification and generalizes the use of the risk score for patients with T2D and ACS. Future validation studies in ACS populations may be warranted.

Narcotics Anonymous members in recovery from methamphetamine use disorder.

BACKGROUND AND OBJECTIVES: Methamphetamine use disorder (MUD) is a major public health problem, but there are no evidence-based, best-practice, pharmacologic, or behavioral treatments for it. Narcotics Anonymous (NA) may provide an option for referral for such patients. METHODS: Two waves of surveys were sent to a sample of NA members to evaluate demographic, drug use, and NA-related issues. Of 4445 responses received from US residents, 647 listed themselves as abstinent from their worst drug problem, methamphetamine. Twelve possible sources of support were scored by these latter respondents for how important each was for their own recovery. RESULTS: Methamphetamine respondents were longstanding NA members, with their first NA meeting 30.2 years ago, 84.3% having served as sponsors for other members, and with little current craving (0.65 out of 10). Although now abstinent for an average of 13.4 years, at some point over the course of the membership, 47.4% had experienced a relapse, for an average of 16.7 months. In a factor analysis of resources scored, 29.6% of the variance fell under NA social and 29.2% spiritual; and 11.8% under outside professional support. DISCUSSION AND CONCLUSIONS: NA served as a resource for supporting abstinence for some members with MUD. They scored social resources of NA support higher than both spiritual and outside institutional ones. SCIENTIFIC SIGNIFICANCE: NA can serve as a community-based resource for MUD. Determining the nature of recovery that members with MUD have in NA can be useful for further research of socially grounded support for recovery in substance use disorders.

Current Advancements in Mouse Models of Retinal Disease.

The field of retinal degenerative (RDs) disease study has been in a state of exponential growth from discovering the underlying genetic components of such diseases as age-related macular degeneration (AMD) and retinitis pigmentosa (RP) to the first gene therapy developed and approved for human Leber congenital amaurosis. However, a source for high-fidelity animal models of these complex, multifactorial, and/or polygenic diseases is a need that has yet to be fulfilled. While models for AMD and RP do exist, they often require aging the animals for a year or more, feeding special diets, or introduction of external modulators such as exposure to cigarette smoke. Currently, work is being done to uncover high-fidelity naturally occurring models of these retinal diseases with the hope and intent of providing the vision community the tools it needs to better understand, treat, and, one day, cure the patients suffering from these devastating afflictions.

Internal and External Resources Relied on by Established Twelve Step Fellowship Members for Their Recoveries.

Background: The Twelve Steps described by Narcotics Anonymous (NA) and Alcoholics Anonymous denote key aspects of how members can achieve abstinence from alcohol and other drugs. However, there are limited empirical findings on what long-term members rely on to support their ongoing recovery.Method: In order to clarify the members' reliance on those latter resources, we surveyed 2,293 long-term NA members through the internet on items they rely on for their recovery. They scored nine NA-related resources (e.g., their sponsor) and three non-NA institutional ones (e.g., a professional therapist).Results: Three factors accounted for 53.6% of the variance in the respondents' scores of the 12 items. We labeled them, with the percent of variance accorded, as NA-based social (24.9%) support, spiritual (17.8%) support, and outside professional (10.9%) help. While NA-based resources ranked highest, outside resources (a house of worship, a therapist, or medications for psychological distress) were scored by 75.4% of the respondents. Analysis by subgroups of respondents reflected the diversity of resources members draw on. The use of internet-based meetings during the COVID-19 period reflected the resilience of the NA format.Conclusion: Members of Twelve Step programs can be studied to shed light on options that they rely on for support for their ongoing recovery, both within the fellowships and outside them. Long-term members can apparently rely on resources inside the fellowship and simultaneously on professional ones, as well. These findings can be helpful for researchers in considering mechanisms that underlie long-term Twelve Step-related recovery and for clinicians in employing both these fellowships and outside resources as adjuncts to their professional care.

Timing and Outcomes After Coronary Angiography Following Out-of-Hospital Cardiac Arrest Without Signs of ST-Segment Elevation Myocardial Infarction.

BACKGROUND: There is broad consensus that resuscitated out-of-hospital cardiac arrest (OHCA) patients with ST-segment elevation myocardial infarction (STEMI) should receive immediate coronary angiography (CAG); however, factors that guide patient selection and optimal timing of CAG for post-arrest patients without evidence of STEMI remain incompletely described. OBJECTIVE: We sought to describe the timing of post-arrest CAG in actual practice, patient characteristics associated with decision to perform immediate vs. delayed CAG, and patient outcomes after CAG. METHODS: We conducted a retrospective cohort study at seven U.S. academic hospitals. Resuscitated adult patients with OHCA were included if they presented between January 1, 2015 and December 31, 2019 and received CAG during hospitalization. Emergency medical services run sheets and hospital records were analyzed. Patients without evidence of STEMI were grouped and compared based on time from arrival to CAG performance into "early" (≤ 6 h) and "delayed" (> 6 h). RESULTS: Two hundred twenty-one patients were included. Median time to CAG was 18.6 h (interquartile range [IQR] 1.5-94.6 h). Early catheterization was performed on 94 patients (42.5%) and delayed catheterization was performed on 127 patients (57.5%). Patients in the early group were older (61 years [IQR 55-70 years] vs. 57 years [IQR 47-65] years) and more likely to be male (79.8% vs. 59.8%). Those in the early group were more likely to have clinically significant lesions (58.5% vs. 39.4%) and receive revascularization (41.5% vs. 19.7%). Patients were more likely to die in the early group (47.9% vs. 33.1%). Among survivors, there was no significant difference in neurologic recovery at discharge. CONCLUSIONS: OHCA patients without evidence of STEMI who received early CAG were older and more likely to be male. This group was more likely to have intervenable lesions and receive revascularization.

Three-Dimensional Virtual Reality Spinal Cord Stimulator Training Improves Trainee Procedural Confidence and Performance.

OBJECTIVE: This study evaluates the use of a three-dimensional virtual reality spinal cord stimulator (SCS) training system to enhance trainee confidence and technical proficiency with interlaminar epidural access and SCS placement. MATERIALS AND METHODS: A total of 14 trainees comprising pain fellows and residents were recruited. Experience and confidence levels were established through pre- and postsurveys. Each trainee performed two sessions placing SCS leads using the training device. In between attempts, a standardized teaching session was performed with the simulator. Performance during each attempt was assessed through objective measures such as needle angle and an evaluation rubric Pain Procedure Rating System (PaPRS). Statistical analysis was performed through paired sample t-test to evaluate a single group between separate trials, whereas unpaired t-test was used to assess the difference between the two groups at baseline or within a single trial. RESULTS: Participants had statistically significant improvements in their ability to safely access the epidural space (57.1% improving to 100%, p < 0.01) and to effectively drive percutaneous leads to the target level (7.1% improving to 71.4%, p < 0.001). The mean confidence levels improved by 71.4% for interlaminar epidural access (p < 0.001) and 306% for SCS placement (p < 0.001). The mean procedural efficiency (total procedure time) improved by 43.2% (p < 0.001). The PaPRS total score increased by an average of 73.3% (p < 0.001). CONCLUSIONS: Virtually simulated neuromodulation training is a viable and effective method of augmenting neuromodulation education. Such didactics are options vital for neuromodulation training, given variable exposure during residency and fellowship.