The effect of endothelin a receptor inhibition and biological sex on cutaneous microvascular function in non-Hispanic Black and White young adults.

The purpose of this study was to investigate whether endothelin-A receptor (ETAR) inhibition in non-Hispanic Black (NHB) and White (NHW) young adults depends on biological sex. We recruited females during low hormone (n = 22) and high hormone (n = 22) phases, and males (n = 22). Participants self-identified as NHB (n = 33) or NHW (n = 33). Participants were instrumented with two microdialysis fibers: (1) lactated Ringer's (control) and (2) 500 nM BQ-123 (ETAR antagonist). Local heating was used to elicit cutaneous vasodilation, and an infusion of 20 mM L-NAME to quantify NO-dependent vasodilation. At control sites, NO-dependent vasodilation was lowest in NHB males (46 ± 13 %NO) and NHB females during low hormone phases (47 ± 12 %NO) compared to all NHW groups. Inhibition of ETAR increased NO-dependent vasodilation in NHB males (66 ± 13 %NO), in both groups of females during low hormone phases (NHW, control: 64 ± 12 %NO, BQ-123: 85 ± 11 %NO; NHB, BQ-123: 68 ± 13 %NO), and in NHB females during high hormone phases (control: 61 ± 11 %NO, BQ-123: 83 ± 9 %NO). There was no effect for ETAR inhibition in NHW males or females during high hormone phases. These data suggest the effect of ETAR inhibition on NO-dependent vasodilation is influenced by biological sex and racial identity.

Hand Surgeon Posture: An Evaluation and Factors That Affect It.

Objective: Approximately 68% of orthopaedic surgeons report occupational related musculoskeletal pain, with back pain being the most common. Poor posture while operating has been proven to contribute to these high rates of musculoskeletal pain. There is little research regarding intraoperative surgeon posture within the field of hand and upper extremity surgery. This prospective study aims to investigate and analyze hand surgeon posture in the operating room. Methods: Posture of three hand surgeons was recorded using the UPRIGHT GO posture tracking device while performing a prospective series of 223 hand and upper extremity surgeries. This device reports posture in terms of overall percentage of time spent slouched versus upright. For this cohort of 223 cases, data were collected including surgical procedure, whether the surgery was performed in a seated or standing position, whether or not loupes were worn during the procedure, and if the surgeon was the primary or assistant surgeon. These data were then analyzed to look for any contributing factors to poor posture. Results: The three hand surgeons in this study spent an average of 40.3% of their time slouched while operating. The average percentage of time slouched was significantly greater with the use of loupes versus no loupes. Additionally, mean time slouching was slightly increased when the surgeon was seated and also when the surgeon was acting as the assistant surgeon. Conclusion: The three orthopaedic hand surgeons in our study spent a significant portion of their operative time slouched. The main variable associated with a significant risk of poor surgical posture was wearing loupes. Slight increases in slouching were seen with operating while seated and as the assistant surgeon. Surgeon awareness of these variables, as well as techniques to improve surgeon posture, should be developed in order to help contribute to better surgeon posture within the field of hand surgery.

Beyond methane, new frontiers in anaerobic microbial hydrocarbon utilizing pathways.

Alkanes, single carbon methane to long-chain hydrocarbons (e.g. hexadecane and tetradecane), are important carbon sources to anaerobic microbial communities. In anoxic environments, archaea are known to utilize and produce methane via the methyl-coenzyme M reductase enzyme (MCR). Recent explorations of new environments, like deep sea sediments, that have coupled metagenomics and cultivation experiments revealed divergent MCRs, also referred to as alkyl-coenzyme M reductases (ACRs) in archaea, with similar mechanisms as the C1 utilizing canonical MCR mechanism. These ACR enzymes have been shown to activate other alkanes such as ethane, propane and butane for subsequent degradation. The reversibility of canonical MCRs suggests that these non-methane-activating homologues (ACRs) might have similar reversibility, perhaps mediated by undiscovered lineages that produce alkanes under certain conditions. The discovery of these alternative alkane utilization pathways holds significant promise for a breadth of potential biotechnological applications in bioremediation, energy production and climate change mitigation.

Description of Asgardarchaeum abyssi gen. nov. spec. nov., a novel species within the class Asgardarchaeia and phylum Asgardarchaeota in accordance with the SeqCode.

Asgardarchaeota, commonly referred to as Asgard archaea, is a candidatus phylum-rank archaeal clade that includes the closest archaeal relatives of eukaryotes. Despite their prevalence in the scientific literature, the name Asgardarchaeota lacks nomenclatural validation. Here, we describe a novel high-quality metagenome-assembled genome (MAG), AB3033_2TS, proposed to serve as the nomenclatural type for the species Asgardarchaeum abyssiTS according to the rules of the SeqCode. Based on protein content and compositional features, we infer that A. abyssi AB3033_2TS is an acetogenic chemoheterotroph, possibly a facultative lithoautotroph, and is adapted to a thermophilic lifestyle. Utilizing genomes from Asgard archaea, TACK, and Euryarchaea, we perform phylogenomic reconstructions using the GTDB archaeal marker genes, the current reference set for taxonomic classification. Calibrating relative evolutionary divergence (RED) values for Asgardarchaeota using established Thermoproteota lineages in the GTDB r207 reference tree, we establish a robust classification and propose Asgardarchaeum as the type genus for the family Asgardarchaeaceae (fam. nov)., the order Asgardarchaeales (ord. nov.), the class Asgardarchaeia (class. nov.), and the phylum Asgardarchaeota (phyl. nov.). This effort aims to preserve taxonomic congruence in the scientific literature.

Opposites attract? Mixed-sex parents' and siblings' sport participation differentiates youth athletes' perceived parenting climates.

Guided by family systems and achievement goal theories, this study examined how the sex of athletes and their main sport parents, as well as sport participation patterns (same sport, different sports, and no sports) of parent-athlete and sibling sex compositions (same-sex and mixed-sex), differentiated athlete perceptions of parenting climates-task-involving (emphasizing individual improvements, effort, and mastery) and ego-involving (emphasizing winning and performance comparison). Participants were 353 U.S. high school athletes (Mage = 15.52 and SD = 1.18; 55% male) who completed a survey on perceived parenting climates, family compositions, and sport backgrounds of their parents and siblings. We conducted six moderated regression analyses, two of which used (1) athlete sex and main sport parents' sex, (2) sport participation patterns of parent-athlete sex compositions, or (3) sport participation patterns of sibling sex compositions as independent variables. Four of the analyses were statistically significant with small effect sizes, showing that (1) boys perceived greater ego-involving climates than girls; (2) athletes whose same-sex parents played sports (same or different sports) compared to no sports-perceived greater task-involving climates: (3) athletes whose mixed-sex parents played (same or different sports) compared to no sports-perceived greater task-involving climates and less ego-involving climates; and (4) athletes whose mixed-sex siblings played different sports than they did, compared no sports, and perceived greater task-involving climates. None of the interactions were significant. Findings provide theoretical and practical implications by incorporating motivational climates, addressing the potential relationships of parents' and mixed-sex siblings' sport participation to adaptive parenting climates.

Conflicting patterns of cardiovascular reactivity, self-report, and behavior associated with social anxiety during a conversation with a close friend.

Social anxiety (SA) is characterized by anxious symptomology and fear during social situations, but recent work suggests that SA may not necessarily be associated with negative interpersonal and intrapersonal outcomes in support contexts. The current research investigates the discrepancies between self-perceptions, behavior, and physiological responses associated with SA in social support conversations with close friends. Specifically, we examined the associations between SA and positive and negative affect, perceptions of demands and resources, and responsiveness. Additionally, we used the biopsychosocial model of challenge and threat to understand the physiological responses associated with SA. Participants (79.9% White, 9.8% Black or African American, 10.3% Multiple races or other; 78.7% Female), totaling 172 undergraduate friend dyads, completed self-report measures and had physiological responses recorded while they discussed a problem unrelated to the friendship. Trained coders rated responsive behaviors exhibited during the conversation. Results revealed that greater SA was associated with greater negative perceptions of social interactions (greater negative affect, fewer perceived resources, and greater perceived demands). However, cardiovascular reactivity and behavioral responses within the conversation, as well as perceptions of partners' behavior after the conversation, contrasted with these negative perceptions. Indeed, greater SA was associated with greater sympathetic arousal (indicative of greater task engagement), but not with greater challenge or threat, and SA was not associated with perceived partner responsiveness or responsive behaviors. These results add to the growing body of research that suggests people with greater SA show inconsistencies between their conscious appraisals of social situations and their physiological responses.

Motive and Opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements-an LLMPP study.

Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit": HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of, and mechanisms driving, IG vs non-IG MYC rearrangements have not been elucidated. Here we used custom targeted capture and/or whole genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, while BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because one IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

A retrospective case study of successful translational research: Cardiovascular disease risk assessment, experiences in community engagement.

In underserved communities across New York City, uninsured adults encounter a greater risk of cardiovascular disease (CVD) and diabetes. The Heart-to-Heart Community Outreach Program (H2H) addresses these disparities by screening for CVD risk factors, identifying healthcare access barriers, and fostering community engagement in translational research at the Weill Cornell Medicine Clinical and Translational Science Award (CTSA) hub. Screening events are hosted in partnership with faith-based institutions. Participants provide a medical history, complete a survey, and receive counseling by clinicians with referrals for follow-up care. This study aims to quantify H2H screening participant health status; identify socioeconomic, health access, and health-related barriers disproportionately promoting the onset of CVD and diabetes; and develop long-term community partnerships to enable underserved communities to influence activities across the translational research spectrum at our CTSA hub. The population served is disproportionately non-white, and uninsured, with many low-income and underserved individuals. The program was developed in partnership with our Community Advisory Board to empower this cohort to make beneficial lifestyle changes. Leveraging partnerships with faith-based institutions and community centers in at-risk New York City neighborhoods, H2H addresses the increasing burden of diabetes and CVD risk factors in vulnerable individuals while promoting community involvement in CTSA activities, serving as a model for similar initiatives.

Statistical analyses of ordinal outcomes in randomised controlled trials: a scoping review.

BACKGROUND: Randomised controlled trials (RCTs) aim to estimate the causal effect of one or more interventions relative to a control. One type of outcome that can be of interest in an RCT is an ordinal outcome, which is useful to answer clinical questions regarding complex and evolving patient states. The target parameter of interest for an ordinal outcome depends on the research question and the assumptions the analyst is willing to make. This review aimed to provide an overview of how ordinal outcomes have been used and analysed in RCTs. METHODS: The review included RCTs with an ordinal primary or secondary outcome published between 2017 and 2022 in four highly ranked medical journals (the British Medical Journal, New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association) identified through PubMed. Details regarding the study setting, design, the target parameter, and statistical methods used to analyse the ordinal outcome were extracted. RESULTS: The search identified 309 studies, of which 144 were eligible for inclusion. The most used target parameter was an odds ratio, reported in 78 (54%) studies. The ordinal outcome was dichotomised for analysis in 47 ( 33 % ) studies, and the most common statistical model used to analyse the ordinal outcome on the full ordinal scale was the proportional odds model (64 [ 44 % ] studies). Notably, 86 (60%) studies did not explicitly check or describe the robustness of the assumptions for the statistical method(s) used. CONCLUSIONS: The results of this review indicate that in RCTs that use an ordinal outcome, there is variation in the target parameter and the analytical approaches used, with many dichotomising the ordinal outcome. Few studies provided assurance regarding the appropriateness of the assumptions and methods used to analyse the ordinal outcome. More guidance is needed to improve the transparent reporting of the analysis of ordinal outcomes in future trials.

Mesoscale activity drives the habitat suitability of yellowfin tuna in the Gulf of Mexico.

Yellowfin tuna, Thunnus albacares, represents an important component of commercial and recreational fisheries in the Gulf of Mexico (GoM). We investigated the influence of environmental conditions on the spatiotemporal distribution of yellowfin tuna using fisheries' catch data spanning 2012-2019 within Mexican waters. We implemented hierarchical Bayesian regression models with spatial and temporal random effects and fixed effects of several environmental covariates to predict habitat suitability (HS) for the species. The best model included spatial and interannual anomalies of the absolute dynamic topography of the ocean surface (ADTSA and ADTIA, respectively), bottom depth, and a seasonal cyclical random effect. High catches occurred mainly towards anticyclonic features at bottom depths > 1000 m. The spatial extent of HS was higher in years with positive ADTIA, which implies more anticyclonic activity. The highest values of HS (> 0.7) generally occurred at positive ADTSA in oceanic waters of the central and northern GoM. However, high HS values (> 0.6) were observed in the southern GoM, in waters with cyclonic activity during summer. Our results highlight the importance of mesoscale features for the spatiotemporal distribution of yellowfin tunas and could help to develop dynamic fisheries management strategies in Mexico and the U.S. for this valuable resource.

The Role of Procalcitonin in Predicting Failure of Non-operative Management in Bowel Obstructions.

Procalcitonin has been investigated as a marker for bowel ischemia. This study examined the role of procalcitonin in predicting failure of non-operative management (NOM) in bowel obstructions. Patients with bowel obstructions at a single center from August 2022 to January 2023 were prospectively enrolled (n = 79). Lactic acid (LA) and procalcitonin were collected after surgical consultation. The primary outcome was success or failure of NOM. Univariate analysis, multivariable logistic regression, and performance measures of procalcitonin and LA in predicting bowel ischemia was performed. Of 79 patients included, 48 (61%) required operative intervention during index admission. There were no significant differences in demographics, comorbidities, procalcitonin, nor LA between groups. Time from last bowel movement was associated with failure of NOM (OR 1.03 [95% CI 1.01-1.06]; P = .008), though initial procalcitonin or LA was not. Procalcitonin >.3 ng/mL had acceptable sensitivity in screening for bowel ischemia.

Inhibition of superoxide and iNOS augment cutaneous nitric oxide-dependent vasodilation in non-Hispanic black young adults.

We assessed the combined effect of superoxide and iNOS inhibition on microvascular function in non-Hispanic Black and non-Hispanic White participants (n = 15 per group). Participants were instrumented with four microdialysis fibers: (1) lactated Ringer's (control), (2) 10 µM tempol (superoxide inhibition), (3) 0.1 mM 1400 W (iNOS inhibition), (4) tempol + 1400 W. Cutaneous vasodilation was induced via local heating and NO-dependent vasodilation was quantified. At control sites, NO-dependent vasodilation was lower in non-Hispanic Black (45 ± 9% NO) relative to non-Hispanic White (79 ± 9% NO; p < 0.01; effect size, d = 3.78) participants. Tempol (62 ± 16% NO), 1400 W (78 ± 12% NO) and tempol +1400 W (80 ± 13% NO) increased NO-dependent vasodilation in non-Hispanic Black participants relative to control sites (all p < 0.01; d = 1.22, 3.05, 3.03, respectively). The effect of 1400 W (p = 0.04, d = 1.11) and tempol +1400 W (p = 0.03, d = 1.22) was greater than tempol in non-Hispanic Black participants. There was no difference between non-Hispanic Black and non-Hispanic White participants at 1400 W or tempol + 1400 W sites. These data suggest iNOS has a greater effect on NO-dependent vasodilation than superoxide in non-Hispanic Black participants.

Non-invasive versus invasive respiratory support in preterm infants.

Respiratory insufficiency is almost ubiquitous in infants born preterm, with its incidence increasing with lower gestational age. A wide range of respiratory support management strategies are available for these infants, separable into non-invasive and invasive forms of respiratory support. Here we review the history and evolution of respiratory care for the preterm infant and then examine evidence that has emerged to support a non-invasive approach to respiratory management where able. Continuous positive airway pressure (CPAP) is the non-invasive respiratory support mode currently with the most evidence for benefit. CPAP can be delivered safely and effectively and can commence in the delivery room. Particularly in early life, time spent on non-invasive respiratory support, avoiding intubation and mechanical ventilation, affords benefit for the preterm infant by virtue of a lessening of lung injury and hence a reduction in incidence of bronchopulmonary dysplasia. In recent years, enthusiasm for application of non-invasive support has been further bolstered by new techniques for administration of exogenous surfactant. Methods of less invasive surfactant delivery, in particular with a thin catheter, have allowed neonatologists to administer surfactant without resort to endotracheal intubation. The benefits of this approach appear to be sustained, even in those infants subsequently requiring mechanical ventilation. This cements the notion that any reduction in exposure to mechanical ventilation leads to alleviation of injury to the vulnerable preterm lung, with a long-lasting effect. Despite the clear advantages of non-invasive respiratory support, there will continue to be a role for intubation and mechanical ventilation in some preterm infants, particularly for those born <25 weeks' gestation. It is currently unclear what role early non-invasive support has in this special population, with more studies required.

Using implementation science to decrease variation and high opioid administration in a surgical ICU.

BACKGROUND: High doses and prolonged duration of opioids are associated with tolerance, dependence, and increased mortality. Unfortunately, despite recent efforts to curb outpatient opioid prescribing because of the ongoing epidemic, utilization remains high in the intensive care setting, with intubated patients commonly receiving infusions with a potency much higher than doses required to achieve pain control. We attempted to use implementation science techniques to monitor and reduce excessive opioid prescribing in ventilated patients in our Surgical ICU. METHODS: We conducted a prospective study investigating opioid administration in a closed SICU at an academic medical center over 18 months. Commonly accepted conversions were used to aggregate daily patient opioid use. Patients with a history of chronic opioid use and those being treated with an ICP monitor/drain, neuromuscular blocker, or ECMO were excluded. If the patient spent a portion of a day on a ventilator, that day's total was included in the "vent group." MMEs per patient were collected for each patient and assigned to the on-call intensivist. Intensivists were blinded to the data for the first seven months. They were then provided with academic detailing followed by audit & feedback over the subsequent 11 months, demonstrating how opioid utilization during their time in the SICU compared to the unit average and a blinded list of the other attendings. Student's T-tests were performed to compare opioid utilization before and after initiation of academic detailing and audit & feedback. RESULTS: Opioid utilization in patients on a ventilator decreased by 20.1% during the feedback period, including less variation among all intensivists and a 30.9% reduction by the highest prescribers. CONCLUSION: Implementation science approaches can effectively reduce variation in opioid prescribing, especially for high outliers in a SICU. These interventions may reduce the risks associated with prolonged use of high-dose opioids. LEVEL OF EVIDENCE: Prospective pre-post-intervention, Level II.

Evaluation of Patient Education Materials From Large-Language Artificial Intelligence Models on Carpal Tunnel Release.

BACKGROUND: ChatGPT, an artificial intelligence technology, has the potential to be a useful patient aid, though the accuracy and appropriateness of its responses and recommendations on common hand surgical pathologies and procedures must be understood. Comparing the sources referenced and characteristics of responses from ChatGPT and an established search engine (Google) on carpal tunnel surgery will allow for an understanding of the utility of ChatGPT for patient education. METHODS: A Google search of "carpal tunnel release surgery" was performed and "frequently asked questions (FAQs)" were recorded with their answer and source. ChatGPT was then asked to provide answers to the Google FAQs. The FAQs were compared, and answer content was compared using word count, readability analyses, and content source. RESULTS: There was 40% concordance among questions asked by the programs. Google answered each question with one source per answer, whereas ChatGPT's answers were created from two sources per answer. ChatGPT's answers were significantly longer than Google's and multiple readability analysis algorithms found ChatGPT responses to be statistically significantly more difficult to read and at a higher grade level than Google's. ChatGPT always recommended "contacting your surgeon." CONCLUSION: A comparison of ChatGPT's responses to Google's FAQ responses revealed that ChatGPT's answers were more in-depth, from multiple sources, and from a higher proportion of academic Web sites. However, ChatGPT answers were found to be more difficult to understand. Further study is needed to understand if the differences in the responses between programs correlate to a difference in patient comprehension.