The Effect of Tree Width on Thoracolumbar and Limb Kinematics, Saddle Pressure Distribution, and Thoracolumbar Dimensions in Sports Horses in Trot and Canter

This study evaluated the effect of saddle tree width on thoracolumbar and limb kinematics, saddle pressure distribution, and thoracolumbar epaxial musculature dimensions. Correctly fitted saddles were fitted by a Society of Master Saddler Qualified Saddle Fitter in fourteen sports horses (mean ± SD age 12 ± 8.77 years, height 1.65 ± 0.94 m), and were altered to one width fitting wider and narrower. Horses were equipped with skin markers, inertial measurement units, and a pressure mat beneath the saddle. Differences in saddle pressure distribution, as well as limb and thoracolumbosacral kinematics between saddle widths were investigated using a general linear model with Bonferroni adjusted alpha (p ≤ 0.05). Compared with the correct saddle width, in trot, in the wide saddle, an 8.5% increase in peak pressures was found in the cranial region of the saddle (p = 0.003), a 14% reduction in thoracolumbar dimensions at T13 (p = 0.02), and a 6% decrease in the T13 range of motion in the mediolateral direction (p = 0.02). In the narrow saddle, a 14% increase in peak pressures was found in the caudal region of the saddle (p = 0.01), an 8% decrease in the range of motion of T13 in the mediolateral direction (p = 0.004), and a 6% decrease in the vertical direction (p = 0.004) of T13. Compared with the correct saddle width, in canter, in the wide saddle, axial rotation decreased by 1% at T5 (p = 0.03) with an 5% increase at T13 (p = 0.04) and a 5% increase at L3 (p = 0.03). Peak pressures increased by 4% (p = 0.002) in the cranial region of the wide saddle. Altering the saddle fit had an effect on thoracolumbar kinematics and saddle pressure distribution; hence, correct saddle fit is essential to provide unhindered locomotion

A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation

SETD2-dependent H3 Lysine-36 trimethylation (H3K36me3) has been recently linked to the deposition of de-novo DNA methylation. SETD2 is frequently mutated in cancer, however, the functional impact of SETD2 loss and depletion on DNA methylation across cancer types and tumorigenesis is currently unknown. Here, we perform a pan-cancer analysis and show that both SETD2 mutation and reduced expression are associated with DNA methylation dysregulation across 21 out of the 24 cancer types tested. In renal cancer, these DNA methylation changes are associated with altered gene expression of oncogenes, tumour suppressors, and genes involved in neoplasm invasiveness, including TP53, FOXO1, and CDK4. This suggests a new role for SETD2 loss in tumorigenesis and cancer aggressiveness through DNA methylation dysregulation. Moreover, using a robust machine learning methodology, we develop and validate a 3-CpG methylation signature which is sufficient to predict SETD2 mutation status with high accuracy and correlates with patient prognosis

The effect that induced rider asymmetry has on equine locomotion and the range of motion of the thoracolumbar spine when ridden in rising trot

There is a paucity of evidence on the effect that rider asymmetry has on equine locomotion. The aim of this study was to evaluate the effect of rider asymmetry on equine locomotion by using a novel approach to induce rider asymmetry. Ten non-lame horses were recruited for this study. Joint centre markers were used to capture 2D kinematics (Quintic Biomechanics) of the horse and rider and horses were equipped with seven inertial sensors positioned at the fifth (T5) and eighteenth (T18) thoracic vertebrae, third lumbar (L3) vertebra, tubera sacrale (TS) and left and right tubera coxae. Rider asymmetry was induced by shortening the ventral aspect of one stirrup by 5cm. Kinematic data were compared between conditions using a mixed model with the horse defined as a random factor and stirrup condition (symmetrical stirrups and asymmetrical stirrups) and direction (inside and outside) defined as fixed factors. Data from riders where the right stirrup was shortened was mirrored to reflect a left stirrup being shortened. To determine differences between conditions a significance of P≤0.05 was set. On the rein with the shortened stirrup on the outside: an increase in lateral bending range of motion (ROM) at T5 (P=0.003), L3 (P=0.04) and TS (P=0.02), an increase in mediolateral displacement at T5 (P=0.04), T18 (P=0.04) and L3 (0.03) were found. An increase in maximum fetlock extension was apparent for both the front (P=0.01) and hindlimb (P=0.04) on the contralateral side to the shortened stirrup. For the asymmetrical stirrup condition on the rein with the shortened stirrup on the inside: an increase in flexion-extension ROM at T5 (P=0.03) and L3 (P=0.04), axial rotation at T5 (P=0.05) and lateral bending of T5 (P=0.03), L3 (P=0.04) and TS (P=0.02). Asymmetric rider position appears to have an effect on the kinematics of the thoracolumbar spine. These findings warrant further investigation to understand the long-term impact this may have on equine locomotor health

Is team sport the key to getting everybody active, every day? A systematic review of physical activity interventions aimed at increasing girls' participation in team sport

Background: It is estimated that 21% of boys and 16% of girls in England meet recommended physical activity guidelines. Team sport has the potential to increase physical activity levels; however, studies show that gender-based factors can influence girls’ participation in team sport. Furthermore, evidence for the effectiveness of interventions promoting team sport among girls is limited. This systematic review aimed to assess the impact of physical activity interventions on secondary school-aged girls’ (aged 11-18 years) participation in team sport and to identify potential strategies for increasing participation. Methods: Electronic databases and grey literature were systematically searched for studies of interventions targeting team sport participation among girls in the UK. Results were exported to Refworks, duplicates removed and eligible studies identified. Extracted data included: participant details, such as sample size and age; components of the intervention; outcomes assessed; and each study was quality appraised. Due to heterogeneity across studies, results were presented narratively. Results: Four studies sourced from the grey literature met the inclusion criteria. Findings suggest that physical activity interventions can encourage girls to try new sports, but evidence is limited in relation to sustained participation. Potential strategies for promoting participation included: consultation with girls, implementation of appropriate peer-leaders and friendship group strategies, early intervention and consideration of intervention setting. Conclusions: This review highlights the limited availability of evidence on the effectiveness of physical activity interventions for promoting team sport participation among girls in the UK. Findings indicate that future research is needed to improve the methodological quality of complex intervention evaluation. Physical activity interventions may have the potential to encourage girls to try team sport, but their impact on sustained participation, and subsequent physical activity outcomes, is less apparent

Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4

Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in Africa. The disease typically affects HIV-infected individuals and young children, causing substantial morbidity and mortality. Here we present a genome-wide association study (180 cases, 2677 controls) and replication analysis of NTS bacteraemia in Kenyan and Malawian children. We identify a locus in STAT4, rs13390936, associated with NTS bacteraemia. rs13390936 is a context-specific expression quantitative trait locus for STAT4 RNA expression, and individuals carrying the NTS-risk genotype demonstrate decreased interferon-gamma (IFN gamma) production in stimulated natural killer cells, and decreased circulating IFN gamma concentrations during acute NTS bacteraemia. The NTS-risk allele at rs13390936 is associated with protection against a range of autoimmune diseases. These data implicate interleukin-12-dependent IFN gamma-mediated immunity as a determinant of invasive NTS disease in African children, and highlight the shared genetic architecture of infectious and autoimmune disease.Peer reviewe

Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis

The aim of this study was to investigate the pathogenesis of combination ipilimumab and nivolumab-associated colitis (IN-COL) by measuring gut-derived and peripheral blood mononuclear cell (GMNC; PBMC) profiles. We studied GMNC and PBMC from patients with IN-COL, IN-treated with no adverse-events (IN-NAE), ulcerative colitis (UC) and healthy volunteers using flow cytometry. In the gastrointestinal-derived cells we found high levels of activated CD8+ T cells and mucosal-associated invariant T (MAIT) cells in IN-COL, changes that were not evident in IN-NAE or UC. UC, but not IN-C, was associated with a high proportion of regulatory T cells (Treg). We sought to determine if local tissue responses could be measured in peripheral blood. Peripherally, checkpoint inhibition instigated a rise in activated memory CD4+ and CD8+ T cells, regardless of colitis. Low circulating MAIT cells at baseline was associated with IN-COL patients compared with IN-NAE in one of two cohorts. UC, but not INCOL, was associated with high levels of circulating plasmablasts. In summary, the alterations in T cell subsets measured in IN-COL-affected tissue, characterized by high levels of activated CD8+ T cells and MAIT cells and a low proportion of Treg, reflected a pathology distinct from UC. These tissue changes differed from the periphery, where T cell activation was a widespread on-treatment effect, and circulating MAIT cell count was low but not reliably predictive of colitis

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms