Stereo-Structural Fine Tuning of Chromaticity.

Lanthanoid carboxylates were synthesized, in situ self-assembled in primitive crystals to illustrate temperature-driven evolution in chromaticity. Evolution in structure (crystallinity), composition, luminosity and chromaticity investigated revealing the coupled role of divergence in order/structure (spatial organization), and composition in tuning observed color. Loss of crystallinity or increase in residual carbon leads to decrease in luminosity even with increase in hue. Comparing Ho and Er congeners shows that the density of accessible transitions relates to shifts in low and high wavelength components of color. This work demonstrates that, just as interface dipoles can lead to change in semiconductor bandgap, structure and composition can analogously alter observed color.

The associations between repetitive negative thinking, insomnia symptoms, and sleep quality in adults with a history of trauma.

BACKGROUND: Posttraumatic stress disorder (PTSD) and sleep disturbance are highly comorbid and repetitive negative thinking (RNT) is associated with both sleep disturbance and PTSD. However, few studies have examined the association between RNT and sleep disturbance in individuals exposed to trauma, with and without PTSD. METHOD: Associations between trait-level and trauma-related RNT, insomnia, and sleep quality were investigated in a trauma-exposed MTurk (N = 342) sample. Additionally, PTSD symptom severity was tested as a moderator of the associations between RNT and insomnia and sleep quality. RESULTS: Trait-level RNT predicted poorer sleep quality and greater insomnia, regardless of PTSD severity. Trauma-related RNT was also associated with greater insomnia, though the effect was moderated by PTSD severity such that it was significant for participants with low and moderate, but not severe, PTSD. Both trait- and trauma-related RNT were associated with several specific aspects of sleep quality, including: sleep disturbances, daytime dysfunction, use of sleep medications, sleep onset latency, and subjective sleep quality. CONCLUSIONS: This study demonstrates significant associations linking RNT with insomnia and sleep disturbance in trauma-exposed individuals. Clinically, results suggest that it may be helpful to target both general and trauma-related RNT in sleep interventions for trauma-exposed individuals with insomnia.

High School Follow-Up of the Dating Matters® RCT: Effects on Teen Dating Violence and Relationship Behaviors.

Teen dating violence (TDV) is a significant public health problem that can have lifelong consequences. Using a longitudinal, cluster randomized controlled trial (RCT), this study examines whether the Dating Matters comprehensive prevention model, implemented in middle school, prevented TDV and negative relationship behaviors and promoted positive relationship behaviors in high school (9th-11th grades), when compared with a standard of care intervention. Dating Matters includes programs for sixth to eighth grade youth and their parents, training for school staff, a youth communications program, and policy and data activities implemented in the community. Self-report survey data were collected from students in 46 middle schools that were randomly assigned to condition within site. Students completed two surveys (fall and spring) in each middle school grade and a single survey in the spring of each high school grade. This study examined self-reported TDV perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills in the high school follow-up. While varying patterns emerged, latent panel models demonstrated significant program effects for all outcomes. Dating Matters students reported 19% reduced risk for TDV perpetration, 24% reduced risk for TDV victimization, 7% reduced risk for use of negative conflict strategies, and 3% more use of positive relationship skills, on average across time and cohort, than standard of care students. On average, Dating Matters, implemented in middle school, continued to be more effective at reducing TDV perpetration, TDV victimization, and use of negative conflict resolution strategies in high school than an evidence-based comparison program.Trial Registration: clinicaltrials.gov Identifier: NCT01672541.

Association of chronic poststernotomy pain and health-related quality of life: a prospective cohort study.

PURPOSE: Chronic poststernotomy pain (CPSP) after cardiac surgery is multifactorial and impacts patient recovery. We aimed to evaluate the association between CPSP severity and health-related quality of life at six months after cardiac surgery. METHODS: This was a single-centre prospective cohort study of patients who underwent cardiac surgery with median sternotomy between September 2020 and March 2021. Telephone interviews were conducted at six and 12 months postoperatively using the Short Form McGill Pain Questionnaire and the EQ-5D-5L. Strength of correlation was described using Spearman's correlation coefficient. Multivariable regression analysis was used to account for confounding variables. RESULTS: A total of 252 patients responded to the six-month interview (response rate, 65%). The mean (standard deviation) age of respondents was 65 (13) yr. Twenty-nine percent of respondents (72/252) reported CPSP at six months, and 14% (41/252) reported more than mild pain (score ≥ 2/5). At 12 months, of the 89% (64/72) patients who responded, 47% (30/64) still reported pain. The strength of the correlation between pain scores and EQ-5D-5L was weak (Spearman's correlation coefficient, -0.3). Risk factors for CPSP at six months included higher pain score on postoperative day 1, history of chronic pain prior to surgery, and history of depression. Intraoperative infusion of dexmedetomidine or ketamine was associated with a reduced risk of CPSP at six months. CONCLUSION: Chronic poststernotomy pain still affects patient recovery at six and 12 months after cardiac surgery. The severity of that pain is poorly correlated with patients' quality of life. STUDY REGISTRATION: www.osf.io ( https://osf.io/52rsw ); registered 14 May 2022.

RéSUMé: OBJECTIF: La douleur chronique post-sternotomie (DCPS) après une chirurgie cardiaque est multifactorielle et a un impact sur le rétablissement des patient·es. Nous avons cherché à évaluer l'association entre la sévérité de la DCPS et la qualité de vie liée à la santé six mois après la chirurgie cardiaque. MéTHODE: Il s'agissait d'une étude de cohorte prospective monocentrique portant sur des patient·es ayant bénéficié d'une chirurgie cardiaque avec sternotomie médiane entre septembre 2020 et mars 2021. Des entrevues téléphoniques ont été menées à six et 12 mois après l'opération en se servant du questionnaire abrégé de McGill sur la douleur et de l'EQ-5D-5L. La force de corrélation a été décrite à l'aide du coefficient de corrélation de Spearman. Une analyse de régression multivariée a été utilisée pour tenir compte des variables confondantes. RéSULTATS: Au total, 252 patient·es ont répondu à l'entrevue à six mois (taux de réponse de 65 %). L'âge moyen (écart type) des répondant·es était de 65 (13) ans. Vingt-neuf pour cent des personnes répondantes (72/252) ont déclaré avoir été atteintes de DCPS à six mois, et 14 % (41/252) ont signalé une douleur plus que légère (score ≥ 2/5). À 12 mois, sur les 89 % (64/72) personnes ayant répondu, 47 % (30/64) signalaient encore de la douleur. La force de la corrélation entre les scores de douleur et l'EQ-5D-5L était faible (coefficient de corrélation de Spearman, −0,3). Les facteurs de risque de DCPS à six mois comprenaient un score de douleur plus élevé au jour 1 postopératoire, des antécédents de douleur chronique avant la chirurgie et des antécédents de dépression. Une perfusion peropératoire de dexmédétomidine ou de kétamine a été associée à une réduction du risque de DCPS à six mois. CONCLUSION: La douleur chronique post-sternotomie affecte toujours le rétablissement des patient·es six et 12 mois après la chirurgie cardiaque. La sévérité de cette douleur est faiblement corrélée à la qualité de vie des patient·es. ENREGISTREMENT DE L'éTUDE: www.osf.io ( https://osf.io/52rsw ); enregistrée le 14 mai 2022.

Association Between Anesthesiologist Sex and Patients' Postoperative Outcomes: A Population-based Cohort Study.

OBJECTIVE: To examine the association of anesthesiologist sex on postoperative outcomes. BACKGROUND: Differences in patient postoperative outcomes exist, depending on whether the primary surgeon is male or female, with better outcomes seen among patients treated by female surgeons. Whether the intraoperative anesthesiologist's sex is associated with differential postoperative patient outcomes is unknown. METHODS: We performed a population-based, retrospective cohort study among adult patients undergoing one of 25 common elective or emergent surgical procedures from 2007 to 2019 in Ontario, Canada. We assessed the association between the sex of the intraoperative anesthesiologist and the primary end point of the adverse postoperative outcome, defined as death, readmission, or complication within 30 days after surgery, using generalized estimating equations. RESULTS: Among 1,165,711 patients treated by 3006 surgeons and 1477 anesthesiologists, 311,822 (26.7%) received care from a female anesthesiologist and 853,889 (73.3%) from a male anesthesiologist. Overall, 10.8% of patients experienced one or more adverse postoperative outcomes, of whom 1.1% died. Multivariable adjusted rates of the composite primary end point were higher among patients treated by male anesthesiologists (10.6%) compared with female anesthesiologists (10.4%; adjusted odds ratio 1.02, 95% CI: 1.00-1.05, P =0.048). CONCLUSIONS: We demonstrated a significant association between sex of the intraoperative anesthesiologist and patient short-term outcomes after surgery in a large cohort study. This study supports the growing literature of improved patient outcomes among female practitioners. The underlying mechanisms of why outcomes differ between male and female physicians remain elusive and require further in-depth study.

Frailty: Implications for Neuroanesthesia.

Frailty is increasingly prevalent in the aging neurosurgical population and is an important component of perioperative risk stratification and optimization to reduce complications. Frailty is measured using the phenotypic or deficit accumulation models, with simplified tools most commonly used in studies of neurosurgical patients. There are a limited number of frailty measurement tools that have been validated for individuals with neurological disease, and those that exist are mainly focused on spine pathology. Increasing frailty consistently predicts worse outcomes for patients across a range of neurosurgical procedures, including early complications, disability, non-home discharge, and mortality. Evidence for interventions to improve outcomes for frail neurosurgical patients is limited, and the role of bundled care pathways, prehabilitation, and multidisciplinary involvement requires further investigation. Surgery itself may be an intervention to improve frailty in selected patients, and future research should focus on identifying effective interventions to improve both short-term complications and long-term outcomes.

Estimating the ratio of fatal to non-fatal overdoses involving all drugs, all opioids, synthetic opioids, heroin or stimulants, USA, 2010-2020.

INTRODUCTION: US drug overdose deaths are at historic levels. For every fatal drug overdose, there are many more non-fatal; however, minimal nationally representative data exist on trends in the ratio of fatal to non-fatal drug overdoses and how this differs by drug type. METHODS: Data from the Centers for Disease Control and Prevention's National Vital Statistics System were used to assess the number of fatal overdoses; data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample database were used to estimate the number of non-fatal overdoses treated in emergency departments. Counts of fatal and non-fatal overdoses by drug type (all drug, all opioid, synthetic opioid, heroin, stimulant, and opioid and stimulant polysubstance) were calculated from 2010 to 2020 (for non-fatal synthetic opioid-involved overdoses, from 2016 to 2020 only). Trends in overdose counts and the ratio of fatal to non-fatal overdoses were assessed. RESULTS: On average, counts of fatal overdoses increased quarterly among all drug types, and non-fatal overdoses increased among most drug types. Over the 11-year period, the greatest average quarterly percent change (AQPC) in fatal overdose counts was among synthetic opioid-involved overdoses (AQPC: 7.1%; 95% CI: 6.0 to 8.2) and for non-fatal overdoses was among heroin-involved overdoses (AQPC: 4.3%; 95% CI: 3.9 to 4.8). During 2010‒2020, there was approximately 1 fatal overdose per 15 non-fatal. The ratio of fatal to non-fatal drug overdoses increased among every drug type except heroin; ratio increases were driven by greater relative increases in fatal overdoses compared with non-fatal. CONCLUSIONS: Assessment of the ratio of fatal to non-fatal drug overdoses can be used to understand the lethality of different drugs and inform response and prevention efforts.

The Pelagic Species Trait Database, an open data resource to support trait-based ocean research.

Trait-based frameworks are increasingly used for predicting how ecological communities respond to ongoing global change. As species range shifts result in novel encounters between predators and prey, identifying prey 'guilds', based on a suite of shared traits, can distill complex species interactions, and aid in predicting food web dynamics. To support advances in trait-based research in open-ocean systems, we present the Pelagic Species Trait Database, an extensive resource documenting functional traits of 529 pelagic fish and invertebrate species in a single, open-source repository. We synthesized literature sources and online resources, conducted morphometric analysis of species images, as well as laboratory analyses of trawl-captured specimens to collate traits describing 1) habitat use and behavior, 2) morphology, 3) nutritional quality, and 4) population status information. Species in the dataset primarily inhabit the California Current system and broader NE Pacific Ocean, but also includes pelagic species known to be consumed by top ocean predators from other ocean basins. The aim of this dataset is to enhance the use of trait-based approaches in marine ecosystems and for predator populations worldwide.

Shift From Smoking Cigarettes to Vaping Nicotine in Young Adults.

This survey study assesses trends in nicotine use among young adults in the US between 2013 and 2021.

Effects of Nicotine Content and Preferred Flavor on Subjective Responses to E-cigarettes: A Randomized, Placebo-controlled Laboratory Study.

INTRODUCTION: Evidence suggests that e-liquid flavor and nicotine concentration are important factors in the initiation and maintenance of e-cigarette use (vaping). Flavors may increase the initiation and maintenance of vaping, and nicotine content is a factor in e-cigarette dependence and the efficacy of e-cigarettes for cigarette smoking cessation. Few human laboratory studies have assessed the joint and interactive effects of flavor and nicotine on subjective responses to e-cigarettes. METHODS: Regular e-cigarette users (N = 89) completed a multi-session study involving a paced vaping procedure with e-liquid cartridges containing their preferred flavor (berry, menthol, or tobacco) or no flavor, with or without nicotine (18 mg). Subjective effects of vaping (satisfaction, reward, aversion, airway sensations, and craving relief) were assessed. RESULTS: Nicotine significantly increased psychological reward and craving relief, whereas flavor significantly increased vaping satisfaction and taste. Nicotine dependence severity moderated the effect of nicotine on reward, such that those with the greatest dependence severity reported the greatest reward. CONCLUSIONS: These findings support differential and noninteractive effects of e-liquid nicotine content and flavor on reinforcing effects of e-cigarettes. IMPLICATIONS: E-liquid flavor and nicotine content have independent, non-interactive effects on subjective responses to vaping under controlled laboratory conditions. Among regular e-cigarette users, vaping a preferred flavor increased taste and satisfaction, but did not interact with nicotine to alter reward or craving. Further research on the ways in which these subjective effects may motivate vaping behavior among different populations of e-cigarette users would be useful to inform regulatory policy of ENDS products.

Smoking Cessation Pharmacotherapy Efficacy in Comorbid Medical Populations: Secondary Analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) Randomized Clinical Trial.

INTRODUCTION: This study sought to compare medication efficacy in participants with medical comorbidities who smoke in the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) trial, a double-blind, triple-dummy, placebo- and active-controlled randomized controlled trial. AIMS AND METHODS: Participants were from the U.S. cohort of the main trial and randomized (1:1:1:1) to varenicline, bupropion, nicotine replacement therapy (NRT) patch, or placebo for 12 weeks with follow-up through week 24. Medical comorbidity data were derived from the baseline medical screening questionnaire and categorized into four subgroups (cardiac, respiratory, vascular, and diabetes). Within each comorbidity, generalized linear mixed models were used to assess the association between treatment and continuous abstinence rates from weeks 9-12 to 9-24. Similar models were used to test the effect of number of comorbidities on abstinence. RESULTS: Varenicline resulted in the highest week 12 abstinence rates across all pharmacotherapies and compared to placebo in all comorbidity subgroups: Cardiac (40.0% vs. 3.6%; odds ratios [OR] = 23.3 [5.1-107.1]), respiratory (24.7% vs. 12.8%; OR = 2.2 [1.3-3.8]), vascular (29.1% vs. 10.4%; OR = 3.6 [2.3-5.7]), and diabetes (30.9% vs. 8.3%; OR = 6.5 [2.3-19.0]). This was maintained at week 24 for those with cardiac (23.3% vs. 1.8%; OR = 21.7 [2.7-178.2]), vascular (18.9% vs. 7.1%; OR = 3.1 [1.8-5.3]), and diabetes (20.6% vs. 4.2%; OR = 8.4 [2.1-33.7]) comorbidities. Treatment contrasts within some comorbidity subgroups revealed superior efficacy of varenicline over other pharmacotherapies. All pharmacotherapies increased the odds of abstinence regardless of number of comorbidities. CONCLUSIONS: Varenicline is the most efficacious option for patients with manageable cardiac, respiratory, vascular, and diabetes conditions to quit smoking, supporting recent clinical practice guidelines that recommend varenicline as first-line pharmacotherapy. Bupropion and NRT demonstrated efficacy for some comorbidity subgroups. IMPLICATIONS: This secondary analysis of the EAGLES trial demonstrated that varenicline is the most efficacious option for patients with cardiac, respiratory, vascular, and diabetes diagnoses to quit smoking. This demonstration of varenicline efficacy among individuals with comorbid medical conditions supports recent clinical practice guidelines that recommend varenicline as a first-line pharmacotherapy for smoking cessation.

Photo-Activated Growth and Metastable Phase Transition in Metallic Solid Solutions.

Laser processing in metals is versatile yet limited by its reliance on phase transformation through heating rather than electronic excitation due to their low absorptivity, attributing from highly ordered structures. Metastable states (i.e., surfaces, glasses, undercooled liquids), however, present a unique platform, both energetically and structurally to enable energy landscape tuning through selective stimuli. Herein, this ansatz is demonstrated by exploiting thin passivating oxides to stabilize an undercooled state, followed by photo-perturbation of the near surface order to induce convective Marangoni flows, edge-coalescence and phase transition into a larger metastable solid bearing asymmetric composition between the near surface and core of the formed structure. The self-terminating nature of the process creates a perfectly contained system which can maintain a high relaxation energy barrier hence deep metastable states for extended periods of time.

Effect of a Personalized Tobacco Treatment Intervention on Smoking Abstinence in Individuals Eligible for Lung Cancer Screening.

INTRODUCTION: To determine whether personalized gain-framed messaging and biomarker feedback related to tobacco cessation or reduction decrease smoking behavior in patients undergoing or eligible for lung cancer screening. METHODS: Between 2016 and 2020, 188 patients were enrolled in a two-phase, sequential, randomized controlled trial. Phase 1 evaluated whether standard of care (SC) (five in-person counseling sessions and 8 weeks of nicotine patch) plus gain-framed messaging (GFM) versus SC would increase 8-week biochemically verified smoking cessation rates. In 143 participants randomized in phase 2, we tested whether feedback on smoking-related biomarkers would reduce 6-month self-reported number of cigarettes smoked per day compared with a no feedback control. Chi-square test and mixed effects repeated measures analyses were used to evaluate group differences. RESULTS: Participants were 62.5 ± 5.6 (mean ± SD) years of age, had a 50.3 ± 21 pack-year smoking history, and were smoking 16.9 ± 9.9 cigarettes per day. At 8 weeks, there was no difference in quit rates between those randomized to SC plus GFM (n = 15 of 93, 16.1%) and those randomized to SC (n = 16 of 95, 16.8%), with p equals to 0.90. At the 6-month post-randomization follow-up, number of cigarettes smoked per day was similar in the feedback (least-squares mean = 7.5, 95% confidence interval: 6.0-9.1) and no feedback arms (7.7, 95% confidence interval: 6.2-9.3), with p equals to 0.87. CONCLUSIONS: Gain-framed messaging and health feedback did not significantly improve quit rates relative to comprehensive standard of care. Nevertheless, the overall program achieved clinically meaningful smoking quit rates in this older high pack-year cohort, highlighting the importance of intensive tobacco treatment for patients undergoing lung cancer screening. CLINICAL TRIAL REGISTERED WITH CLINICALTRIALS.GOV: NCT02658032.

Perioperative cortical hand stroke syndrome mimicking peripheral neuropathy: a case report.

PURPOSE: Timely diagnosis of perioperative stroke is challenging, and therapeutic interventions are infrequently offered. The cortical hand syndrome is a rare stroke presentation that results from infarction of the precentral gyrus leading to variable neurologic deficits mimicking peripheral nerve injuries, with no prior reports in the perioperative setting. To raise awareness of this complication among anesthesiologists, we present a case of cortical hand syndrome in a surgical patient initially suspected to have a peripheral neuropathy. CLINICAL FEATURES: A 68-yr-old male with multiple stroke risk factors underwent a nephroureterectomy under general anesthesia and thoracic epidural analgesia for urothelial carcinoma. The patient noted right-hand numbness and weakness to digits 3-5 immediately after surgery and notified his bedside nurse the following day. His symptoms were initially presumed to be a peripheral neuropathy secondary to surgical positioning. Computed tomography of the head the following day revealed an acute cortical infarct in the precentral gyrus consistent with cortical hand stroke syndrome. Subsequent neurologic consultation revealed additional subtle right-sided weakness. Further workup revealed moderate (60-80%) stenosis of the left carotid artery and he underwent a successful carotid endarterectomy one week later. His symptoms had mostly resolved six weeks later. CONCLUSION: Cortical hand stroke syndrome is a rare presentation of perioperative stroke that may be misdiagnosed as a peripheral neuropathy. Our case presentation highlights that perioperative stroke should be considered for patients presenting with neurologic deficits of the hand, particularly those with deficits in multiple peripheral nerve territories and stroke risk factors.

RéSUMé: OBJECTIF: Le diagnostic rapide de l'accident vasculaire cérébral (AVC) périopératoire est difficile, et les interventions thérapeutiques sont rarement proposées. Le syndrome de la main corticale est une présentation rare de l'AVC qui résulte d'un infarctus du gyrus précentral entraînant des déficits neurologiques variables imitant les lésions nerveuses périphériques, sans avoir été préalablement rapporté dans le cadre périopératoire. Afin de sensibiliser les anesthésiologistes à cette complication, nous présentons un cas de syndrome de la main corticale chez un patient chirurgical chez lequel une neuropathie périphérique était initialement suspectée. CARACTéRISTIQUES CLINIQUES: Un homme de 68 ans présentant de multiples facteurs de risque d'AVC a subi une néphro-urétérectomie sous anesthésie générale et une analgésie péridurale thoracique pour un carcinome urothélial. Le patient a remarqué un engourdissement et une faiblesse de la main droite du majeur à l'auriculaire immédiatement après la chirurgie et a avisé le personnel infirmier à son chevet le lendemain. On a d'abord présumé que ses symptômes indiquaient une neuropathie périphérique secondaire au positionnement chirurgical. La tomodensitométrie de la tête réalisée le lendemain a révélé un infarctus cortical aigu dans le gyrus précentral, compatible avec un syndrome d'AVC de la main corticale. Une consultation neurologique ultérieure a révélé une faiblesse subtile supplémentaire du côté droit. Un examen plus approfondi a révélé une sténose modérée (60 à 80 %) de l'artère carotide gauche et le patient a bénéficié d' une endartériectomie carotidienne réussie une semaine plus tard. Ses symptômes avaient pour la plupart disparu six semaines plus tard. CONCLUSION: Le syndrome de l'AVC de la main corticale est une présentation rare d'AVC périopératoire qui peut être diagnostiqué à tort comme une neuropathie périphérique. Notre présentation de cas souligne que l'AVC périopératoire devrait être envisagé chez les patient·es présentant des déficits neurologiques de la main, en particulier chez les personnes présentant des déficits dans plusieurs territoires nerveux périphériques et des facteurs de risque d'AVC.

The Intersection of Race and Sex: A New Perspective Into Diversity Trends in Orthopaedic Surgery.

INTRODUCTION: Studies on diversity in orthopaedic surgery have exclusively examined challenges from a race or sex perspective. This study examines trends in the diversity of entering orthopaedic surgery residents from the intersection of race and sex. METHODS: The American Association of Medical Colleges was queried for individuals entering orthopaedic surgery residencies in the United States from 2001 to 2020. Deidentified data on self-reported sex and race were collected. Proportions by the intersection of sex and race were calculated for 5-year intervals. RESULTS: From 2001 to 2020, most of the new female residents identified as White (mean, 71.0%). The average proportion of White female residents was lower in 2016 to 2020 than in 2001 to 2005 (71.0% vs. 73.2%) but higher than that in 2011 to 2015 (66.8%). The 2016 to 2020 average was lower than that of 2001 to 2005 for those who identified as Asian (11.7% vs. 14.9%), Black (4.1% vs. 4.8%), Hispanic (3.0% vs. 4.4%), and American Indian/Alaska Native (0.0% vs. 1.5%). Most of the new male orthopaedic surgery residents from 2001 to 2020 identified as White (mean, 74.1%), but the average decreased across every 5-year interval from 2001 to 2005 (76.1%) to 2016 to 2020 (71.1%). The 2016 to 2020 average was lower than that of 2001 to 2005 for those who identified as Asian (12.2% vs. 13.6%), Black (3.5% vs. 4.2%), Hispanic (3.0% vs. 3.4%), American Indian/Alaska Native (0.0% vs. 0.6%), and Native Hawaiian/Other Pacific Islander (0.1% vs. 0.3%). In 2020, White male residents made up to 54.2% of new residents. White female residents were the second highest group represented (12.1%). CONCLUSION: Increases in representation were observed for some subgroups of new orthopaedic surgery residents from 2001 to 2020. Although the proportion of both White female and male residents decreased by 11.5% during the 20-year study period, these individuals still made up most of the trainees in 2020. These results underscore the need for conversations and recruitment practices to take into consideration the intersectionality of identities.

Genetic modulation of CWD prion propagation in cervid PrP Drosophila.

Chronic wasting disease is a fatal prion condition of cervids such as deer, elk, moose and reindeer. Secretion and excretion of prion infectivity from North American cervids with this condition causes environmental contamination and subsequent efficient lateral transmission in free-ranging and farmed cervids. Variants of cervid PrP exist that affect host susceptibility to chronic wasting disease. Cervid breeding programmes aimed at increasing the frequency of PrP variants associated with resistance to chronic wasting disease may reduce the burden of this condition in animals and lower the risk of zoonotic disease. This strategy requires a relatively rapid and economically viable model system to characterise and support selection of prion disease-modifying cervid PrP variants. Here, we generated cervid PrP transgenic Drosophila to fulfil this purpose. We have generated Drosophila transgenic for S138 wild type cervid PrP, or the N138 variant associated with resistance to chronic wasting disease. We show that cervid PrP Drosophila accumulate bona fide prion infectivity after exposure to cervid prions. Furthermore, S138 and N138 PrP fly lines are susceptible to cervid prion isolates from either North America or Europe when assessed phenotypically by accelerated loss of locomotor ability or survival, or biochemically by accumulation of prion seeding activity. However, after exposure to European reindeer prions, N138 PrP Drosophila accumulated prion seeding activity with slower kinetics than the S138 fly line. These novel data show that prion susceptibility characteristics of cervid PrP variants are maintained when expressed in Drosophila, which highlights this novel invertebrate host in modelling chronic wasting disease.

Platelet factors attenuate inflammation and rescue cognition in ageing.

Identifying therapeutics to delay, and potentially reverse, age-related cognitive decline is critical in light of the increased incidence of dementia-related disorders forecasted in the growing older population1. Here we show that platelet factors transfer the benefits of young blood to the ageing brain. Systemic exposure of aged male mice to a fraction of blood plasma from young mice containing platelets decreased neuroinflammation in the hippocampus at the transcriptional and cellular level and ameliorated hippocampal-dependent cognitive impairments. Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals. Systemic administration of exogenous PF4 attenuated age-related hippocampal neuroinflammation, elicited synaptic-plasticity-related molecular changes and improved cognition in aged mice. We implicate decreased levels of circulating pro-ageing immune factors and restoration of the ageing peripheral immune system in the beneficial effects of systemic PF4 on the aged brain. Mechanistically, we identified CXCR3 as a chemokine receptor that, in part, mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain. Together, our data identify platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.

A new Hoxb8FlpO mouse line for intersectional approaches to dissect developmentally defined adult sensorimotor circuits.

Improvements in the speed and cost of expression profiling of neuronal tissues offer an unprecedented opportunity to define ever finer subgroups of neurons for functional studies. In the spinal cord, single cell RNA sequencing studies support decades of work on spinal cord lineage studies, offering a unique opportunity to probe adult function based on developmental lineage. While Cre/Flp recombinase intersectional strategies remain a powerful tool to manipulate spinal neurons, the field lacks genetic tools and strategies to restrict manipulations to the adult mouse spinal cord at the speed at which new tools develop. This study establishes a new workflow for intersectional mouse-viral strategies to dissect adult spinal function based on developmental lineages in a modular fashion. To restrict manipulations to the spinal cord, we generate a brain-sparing Hoxb8FlpO mouse line restricting Flp recombinase expression to caudal tissue. Recapitulating endogenous Hoxb8 gene expression, Flp-dependent reporter expression is present in the caudal embryo starting day 9.5. This expression restricts Flp activity in the adult to the caudal brainstem and below. Hoxb8FlpO heterozygous and homozygous mice do not develop any of the sensory or locomotor phenotypes evident in Hoxb8 heterozygous or mutant animals, suggesting normal developmental function of the Hoxb8 gene and protein in Hoxb8FlpO mice. Compared to the variability of brain recombination in available caudal Cre and Flp lines, Hoxb8FlpO activity is not present in the brain above the caudal brainstem, independent of mouse genetic background. Lastly, we combine the Hoxb8FlpO mouse line with dorsal horn developmental lineage Cre mouse lines to express GFP in developmentally determined dorsal horn populations. Using GFP-dependent Cre recombinase viruses and Cre recombinase-dependent inhibitory chemogenetics, we target developmentally defined lineages in the adult. We show how developmental knock-out versus transient adult silencing of the same ROR𝛃 lineage neurons affects adult sensorimotor behavior. In summary, this new mouse line and viral approach provides a blueprint to dissect adult somatosensory circuit function using Cre/Flp genetic tools to target spinal cord interneurons based on genetic lineage.