A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses

Background: Thoroughbred racehorses are subject to non-traumatic distal limb bone fractures that occur during racing and exercise. Susceptibility to fracture may be due to underlying disturbances in bone metabolism which have a genetic cause. Fracture risk has been shown to be heritable in several species but this study is the first genetic analysis of fracture risk in the horse. Results: Fracture cases (n = 269) were horses that sustained catastrophic distal limb fractures while racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were over 4 years of age, were racing during the same time period as the cases, and had no history of fracture at the time the study was carried out. The horses sampled were bred for both flat and National Hunt (NH) jump racing. 43,417 SNPs were employed to perform a genome-wide association analysis and to estimate the proportion of genetic variance attributable to the SNPs on each chromosome using restricted maximum likelihood (REML). Significant genetic variation associated with fracture risk was found on chromosomes 9, 18, 22 and 31. Three SNPs on chromosome 18 (62.05 Mb – 62.15 Mb) and one SNP on chromosome 1 (14.17 Mb) reached genome-wide significance (p <0.05) in a genome-wide association study (GWAS). Two of the SNPs on ECA 18 were located in a haplotype block containing the gene zinc finger protein 804A (ZNF804A). One haplotype within this block has a protective effect (controls at 1.95 times less risk of fracture than cases, p = 1 × 10-4), while a second haplotype increases fracture risk (cases at 3.39 times higher risk of fracture than controls, p = 0.042). Conclusions: Fracture risk in the Thoroughbred horse is a complex condition with an underlying genetic basis. Multiple genomic regions contribute to susceptibility to fracture risk. This suggests there is the potential to develop SNP-based estimators for genetic risk of fracture in the Thoroughbred racehorse, using methods pioneered in livestock genetics such as genomic selection. This information would be useful to racehorse breeders and owners, enabling them to reduce the risk of injury in their horses

Doc’Apella: A Vocal Performance Group Designed to Reduce Stress And Prevent Burnout Among Medical and Health Sciences Students

Introduction: Burnout is common among health professions trainees characterized by emotional exhaustion induced by repeated stressors. Although traditional stress management activities to promote wellness are effective in reducing stress short-term, alternative approaches are needed with the potential for long-term impact. To address burnout among students at the University of Nebraska Medical Center (UNMC), a vocal group was formed to provide a creative outlet. The purpose of this study was to determine the students’ motivation for joining Doc’Apella and assess the impact on burnout. Methods: Students enrolled in a health sciences program were invited to participate during the 2018-19 academic year (August-May). Two volunteer students arranged the music, recorded individual practice tracks, and directed the group during rehearsals two nights/week from 5:30-6:30. Group members selected arrangements and performed in a variety of settings. At the end of the year, participants were invited to complete an anonymous online survey. Results: Of the 98 students on the roster, 18 (18.4%) responded to the survey. Participants included medical students (n = 9, 50.0%), three graduate students (16.7%), two public health students (11.1%), one pharmacy student (5.5%), and three classified as “other” (16.7%). Nine (50.0%) indicated the aspect of the group that was MOST important was “escaping my stress or frustration with a creative activity.” Thirteen (72.2%) felt Doc’Apella was very or extremely beneficial to their “own sense of wellbeing” and 94.4% (n = 17) reported Doc’Apella “helped reduce stress and burnout” somewhat or very much. Conclusion: Creating music with others may provide an effective way for medical trainees to not only to express creative energy but also to connect with others across health professions. Although the results support structured creative activities to reduce stress and burnout, a large-scale study is needed will strengthen empirical evidence and highlight the impact for health professions trainees

Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison

EXPAREL (bupivacaine extended-release liposome injection), DepoFoam bupivacaine, is in development for prolonged postsurgical analgesia. Repeat-dose toxicity studies were conducted in rabbits and dogs to compare the potential local and systemic toxicities of EXPAREL and bupivacaine HCl (Bsol), and the reversibility of any effects. Dogs tolerated much larger doses than rabbits. EXPAREL-related minimal-to-moderate granulomatous inflammation was noted at the injection sites. In recovery animals, the granulomatous inflammation was observed less frequently and was characterized by an increased number of multinucleated giant cells. These effects were considered a normal response to liposomes and nonadverse. Rabbits are more sensitive than dogs. In rabbits, convulsions were noted with EXPAREL and more frequently with Bsol; a NOAEL was not identified. In dogs, EXPAREL was well tolerated (NOAEL > 30 mg/kg/dose). The cumulative exposure of EXPAREL in these studies is well in excess of the proposed maximum single-dose exposure that is intended in humans

The Safety of EXPAREL ® (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs

A sustained-release DepoFoam injection formulation of bupivacaine (EXPAREL, 15 mg/mL) is currently being investigated for postsurgical analgesia via peripheral nerve block (PNB). Single-dose toxicology studies of EXPAREL (9, 18, and 30 mg/kg), bupivacaine solution (Bsol, 9 mg/kg), and saline injected around the brachial plexus nerve bundle were performed in rabbits and dogs. The endpoints included clinical pathology, pharmacokinetics, and histopathology evaluation on Day 3 and Day 15 (2/sex/group/period). EXPAREL resulted in a nearly 4-fold lower Cmax versus Bsol at the same dose. EXPAREL was well tolerated at doses up to 30 mg/kg. The only EXPAREL-related effect seen was minimal to mild granulomatous inflammation of adipose tissue around nerve roots (8 of 24 rabbits and 7 of 24 dogs) in the brachial plexus sites. The results indicate that EXPAREL was well tolerated in these models and did not produce nerve damage after PNB in rabbits and dogs

Interactions between the Physical and Social Environments with Adverse Pregnancy Events Related to Placental Disorders—A Scoping Review

Background: Due to different social and physical environments across Africa, understanding how these environments differ in interacting with placental disorders will play an important role in developing effective interventions. Methods: A scoping review was conducted, to identify current knowledge on interactions between the physical and social environment and the incidence of placental disease in Africa. Results: Heavy metals were said to be harmful when environmental concentrations are beyond critical limits. Education level, maternal age, attendance of antenatal care and parity were the most investigated social determinants. Conclusions: More evidence is needed to determine the relationships between the environment and placental function in Africa. The results show that understanding the nature of the relationship between social determinants of health (SDH) and placental health outcomes plays a pivotal role in understanding the risk in the heterogenous communities in Africa

Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children

OBJECTIVES: To examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD. STUDY DESIGN: A multicenter, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weight was categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with the birth weight distribution in the general US population. The severity of liver histology was assessed by birth weight category. RESULTS: Children with NAFLD (n = 538) had overrepresentation of both LBW and HBW compared with the general US population (LBW, 9.3%; NBW, 75.8%; HBW, 14.9% vs LBW, 6.1%; NBW, 83.5%; HBW 10.5%; P < .0001). Children with HBW had significantly greater odds of having more severe steatosis (OR, 1.82, 95% CI. 1.15-2.88) and nonalcoholic steatohepatitis (OR, 2.03; 95% CI, 1.21-3.40) compared with children with NBW. In addition, children with NAFLD and LBW had significantly greater odds of having advanced fibrosis (OR, 2.23; 95% CI, 1.08-4.62). CONCLUSION: Birth weight involves maternal and in utero factors that may have long-lasting consequences. Children with both LBW and HBW may be at increased risk for developing NAFLD. Among children with NAFLD, those with LBW or HBW appear to be at increased risk for more severe disease

Strong margin influence on the Arctic Ocean Barium Cycle revealed by pan‐Arctic synthesis

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Whitmore, L., Shiller, A., Horner, T., Xiang, Y., Auro, M., Bauch, D., Dehairs, F., Lam, P., Li, J., Maldonado, M., Mears, C., Newton, R., Pasqualini, A., Planquette, H., Rember, R., & Thomas, H. Strong margin influence on the Arctic Ocean Barium Cycle revealed by pan‐Arctic synthesis. Journal of Geophysical Research: Oceans, 127(4), (2022): e2021JC017417, https://doi.org/10.1029/2021jc017417.Early studies revealed relationships between barium (Ba), particulate organic carbon and silicate, suggesting applications for Ba as a paleoproductivity tracer and as a tracer of modern ocean circulation. But, what controls the distribution of barium (Ba) in the oceans? Here, we investigated the Arctic Ocean Ba cycle through a one-of-a-kind data set containing dissolved (dBa), particulate (pBa), and stable isotope Ba ratio (δ138Ba) data from four Arctic GEOTRACES expeditions conducted in 2015. We hypothesized that margins would be a substantial source of Ba to the Arctic Ocean water column. The dBa, pBa, and δ138Ba distributions all suggest significant modification of inflowing Pacific seawater over the shelves, and the dBa mass balance implies that ∼50% of the dBa inventory (upper 500 m of the Arctic water column) was supplied by nonconservative inputs. Calculated areal dBa fluxes are up to 10 μmol m−2 day−1 on the margin, which is comparable to fluxes described in other regions. Applying this approach to dBa data from the 1994 Arctic Ocean Survey yields similar results. The Canadian Arctic Archipelago did not appear to have a similar margin source; rather, the dBa distribution in this section is consistent with mixing of Arctic Ocean-derived waters and Baffin Bay-derived waters. Although we lack enough information to identify the specifics of the shelf sediment Ba source, we suspect that a sedimentary remineralization and terrigenous sources (e.g., submarine groundwater discharge or fluvial particles) are contributors.This research was supported by the National Science Foundation [OCE-1434312 (AMS), OCE-1436666 (RN), OCE-1535854 (PL), OCE-1736949, OCE-2023456 (TJH), and OCE-1829563 (R. Anderson for open access support)], Natural Sciences and Engineering Research Council of Canada (NSERC)-Climate Change and Atmospheric Research (CCAR) Program (MTM), and LEFE-CYBER EXPATE (HP). HT acknowledges support by the Canadian GEOTRACES via NSERC-CCAR and the German Academic Exchange Service (DAAD): MOPGA-GRI (Make Our Planet Great Again—Research Initiative) sponsored by BMBF (Federal German Ministry of Education and Research; Grant No. 57429828)

Strong Margin Influence on the Arctic Ocean Barium Cycle Revealed by Pan‐Arctic Synthesis

Laura M. Whitmore et al, 2022, Strong margin influence on the Arctic Ocean barium cycle revealed by Pan‐Arctic synthesis, Journal of Geophysical Research: Oceans, Citation number, 10.1029/2021JC017417. To view the published open abstract, go to https://doi.org/10.1029/2021JC017417

ALS Specific cognitive and behaviour changes associated with advancing disease stage in ALS

Objective To elucidate the relationship between disease stage in amyotrophic lateral sclerosis (ALS), as measured with the King’s Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Methods A large multicenter observational cohort of 161 cross-sectional patients with ALS and 80 healthy matched controls were recruited across 3 research sites (Dublin, Edinburgh, and London). Participants were administered the ECAS and categorized into independent groups based on their King’s clinical disease stage at time of testing. Results Significant differences were observed between patients and controls on all subtests of the ECAS except for visuospatial functioning. A significant cross-sectional effect was observed across disease stages for ALS-specific functions (executive, language, letter fluency) and ECAS total score but not for ALS-nonspecific functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral change were also related to disease stage. The relationship between cognitive function and disease stage may be due to letter fluency impairment, whereas higher rates of all behavioral domains were seen in later King’s stage. The presence of bulbar signs, but not site of onset, was significantly related to ALS-specific, ECAS total, and behavioral scores. Conclusion ALS-specific cognitive deficits and behavioral impairment are more frequent with more severe disease stage. By end-stage disease, only a small percentage of patients are free of neuropsychological impairment. The presence of bulbar symptoms exaggerates the differences observed between disease stages. These findings suggest that cognitive and behavioral change should be incorporated into ALS diagnostic criteria and should be included in future staging systems