Functional Locomotor Consequences of Uneven Forefeet for Trot Symmetry in Individual Riding Horses

ABSTRACT: Left-right symmetrical distal limb conformation can be an important prerequisite for a successful performance, and it is often hypothesized that asymmetric or uneven feet are important enhancing factors for the development of lameness. On a population level, it has been demonstrated that uneven footed horses are retiring earlier from elite level competition, but the biomechanical consequences are not yet known. The objectives of this study were to compare the functional locomotor asymmetries of horses with uneven to those with even feet. Hoof kinetics and distal limb kinematics were collected from horses (n = 34) at trot. Dorsal hoof wall angle was used to classify horses as even or uneven (1.5° difference between forefeet respectively) and individual feet as flat (55°). Functional kinetic parameters were compared between even and uneven forefeet using MANOVA followed by ANOVA. The relative influences of differences in hoof angle between the forefeet and of absolute hoof angle on functional parameters were analysed using multiple regression analysis (P<0.05). In horses with uneven feet, the side with the flatter foot showed a significantly larger maximal horizontal braking and vertical ground reaction force, a larger vertical fetlock displacement and a suppler fetlock spring. The foot with a steeper hoof angle was linearly correlated with an earlier braking-propulsion transition. The conformational differences between both forefeet were more important for loading characteristics than the individual foot conformation of each individual horse. The differences in vertical force and braking force between uneven forefeet could imply either an asymmetrical loading pattern without a pathological component or a subclinical lameness as a result of a pathological development in the steeper foot

The impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis

BACKGROUND: The burden of psychiatric symptoms in Parkinson's disease includes depression, anxiety, apathy, psychosis, and impulse control disorders. However, the relationship between psychiatric comorbidities and subsequent prognosis and neurological outcomes is not yet well understood. In this systematic review and meta-analysis, in individuals with Parkinson's disease, we aimed to characterise the association between specific psychiatric comorbidities and subsequent prognosis and neurological outcomes: cognitive impairment, death, disability, disease progression, falls or fractures and care home admission. METHODS: We searched MEDLINE, Embase, PsycINFO and AMED up to 13th November 2023 for longitudinal observational studies which measured disease outcomes in people with Parkinson's disease, with and without specific psychiatric comorbidities, and a minimum of two authors extracted summary data. Studies of individuals with other parkinsonian conditions and those with outcome measures that had high overlap with psychiatric symptoms were excluded to ensure face validity. For each exposure-outcome pair, a random-effects meta-analysis was conducted based on standardised mean difference, using adjusted effect sizes–where available–in preference to unadjusted effect sizes. Study quality was assessed using the Newcastle–Ottawa Scale. Between-study heterogeneity was assessed using the I2 statistic and publication bias was assessed using funnel plots. PROSPERO Study registration number: CRD42022373072. FINDINGS: There were 55 eligible studies for inclusion in meta-analysis (n = 165,828). Data on participants’ sex was available for 164,514, of whom 99,182 (60.3%) were male and 65,460 (39.7%) female. Study quality was mostly high (84%). Significant positive associations were found between psychosis and cognitive impairment (standardised mean difference [SMD] 0.44, [95% confidence interval [CI] 0.23–0.66], I2 30.9), psychosis and disease progression (SMD 0.46, [95% CI 0.12–0.80], I2 70.3%), depression and cognitive impairment (SMD 0.37 [95% CI 0.10–0.65], I2 27.1%), depression and disease progression (SMD 0.46 [95% CI 0.18–0.74], I2 52.2), depression and disability (SMD 0.42 [95% CI 0.25–0.60], I2 7.9%), and apathy and cognitive impairment (SMD 0.60 [95% CI 0.02–1.19], I2 27.9%). Between-study heterogeneity was moderately high. INTERPRETATION: Psychosis, depression, and apathy in Parkinson's disease are all associated with at least one adverse outcome, including cognitive impairment, disease progression and disability. Whether this relationship is causal is not clear, but the mechanisms underlying these associations require exploration. Clinicians should consider these psychiatric comorbidities to be markers of a poorer prognosis in people with Parkinson's disease. Future studies should investigate the underlying mechanisms and which treatments for these comorbidities may affect Parkinson's disease outcomes. FUNDING: Wellcome Trust, UK National Institute for Health Research (NIHR), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at University College London Hospitals NHS Foundation Trust, National Brain Appeal

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

A Passerine Bird's Evolution Corroborates the Geologic History of the Island of New Guinea

New Guinea is a biologically diverse island, with a unique geologic history and topography that has likely played a role in the evolution of species. Few island-wide studies, however, have examined the phylogeographic history of lowland species. The objective of this study was to examine patterns of phylogeographic variation of a common and widespread New Guinean bird species (Colluricincla megarhyncha). Specifically, we test the mechanisms hypothesized to cause geographic and genetic variation (e.g., vicariance, isolation by distance and founder-effect with dispersal). To accomplish this, we surveyed three regions of the mitochondrial genome and a nuclear intron and assessed differences among 23 of the 30 described subspecies from throughout their range. We found support for eight highly divergent lineages within C. megarhyncha. Genetic lineages were found within continuous lowland habitat or on smaller islands, but all individuals within clades were not necessarily structured by predicted biogeographic barriers. There was some evidence of isolation by distance and potential founder-effects. Mitochondrial DNA sequence divergence among lineages was at a level often observed among different species or even genera of birds (5–11%), suggesting lineages within regions have been isolated for long periods of time. When topographical barriers were associated with divergence patterns, the estimated divergence date for the clade coincided with the estimated time of barrier formation. We also found that dispersal distance and range size are positively correlated across lineages. Evidence from this research suggests that different phylogeographic mechanisms concurrently structure lineages of C. megarhyncha and are not mutually exclusive. These lineages are a result of evolutionary forces acting at different temporal and spatial scales concordant with New Guinea's geological history

The Causal Cascade to Multiple Sclerosis: A Model for MS Pathogenesis

BACKGROUND: MS pathogenesis seems to involve both genetic susceptibility and environmental risk factors. Three sequential factors are implicated in the environmental risk. The first acts near birth, the second acts during childhood, and the third acts long thereafter. Two candidate factors (vitamin D deficiency and Epstein-Barr viral infection) seem well suited to the first two environmental events. METHODOLOGY/PRINCIPAL FINDINGS: A mathematical Model for MS pathogenesis is developed, incorporating these environmental and genetic factors into a causal scheme that can explain some of the recent changes in MS-epidemiology (e.g., increasing disease prevalence, a changing sex-ratio, and regional variations in monozygotic twin concordance rates). CONCLUSIONS/SIGNIFICANCE: This Model suggests that genetic susceptibility is overwhelmingly the most important determinant of MS pathogenesis. Indeed, over 99% of individuals seem genetically incapable of developing MS, regardless of what environmental exposures they experience. Nevertheless, the contribution of specific genes to MS-susceptibility seems only modest. Thus, despite HLA DRB1*1501 being the most consistently identified genetic marker of MS-susceptibility (being present in over 50% of northern MS patient populations), only about 1% of individuals with this allele are even genetically susceptible to getting MS. Moreover, because genetic susceptibility seems so similar throughout North America and Europe, environmental differences principally determine the regional variations in disease characteristics. Additionally, despite 75% of MS-patients being women, men are 60% more likely to be genetically-susceptible than women. Also, men develop MS at lower levels of environmental exposure than women. Nevertheless, women are more responsive to the recent changes in environmental-exposure (whatever these have been). This explains both the changing sex-ratio and the increasing disease prevalence (which has increased by a minimum of 32% in Canada over the past 35 years). As noted, environmental risk seems to result from three sequential components of environmental exposure. The potential importance of this Model for MS pathogenesis is that, if correct, a therapeutic strategy, designed to interrupt one or more of these sequential factors, has the potential to markedly reduce or eliminate disease prevalence in the future

Conspicuous Female Ornamentation and Tests of Male Mate Preference in Threespine Sticklebacks (Gasterosteus aculeatus)

Sexual selection drives the evolution of exaggerated male ornaments in many animal species. Female ornamentation is now acknowledged also to be common but is generally less well understood. One example is the recently documented red female throat coloration in some threespine stickleback (Gasterosteus aculeatus) populations. Although female sticklebacks often exhibit a preference for red male throat coloration, the possibility of sexual selection on female coloration has been little studied. Using sequential and simultaneous mate choice trials, we examined male mate preferences for female throat color, as well as pelvic spine color and standard length, using wild-captured threespine sticklebacks from the Little Campbell River, British Columbia. In a multivariate analysis, we found no evidence for a population-level mate preference in males, suggesting the absence of directional sexual selection on these traits arising from male mate choice. Significant variation was detected among males in their preference functions, but this appeared to arise from differences in their mean responsiveness across mating trials and not from variation in the strength (i.e., slope) of their preference, suggesting the absence of individual-level preferences as well. When presented with conspecific intruder males, male response decreased as intruder red throat coloration increased, suggesting that males can discriminate color and other aspects of phenotype in our experiment and that males may use these traits in intrasexual interactions. The results presented here are the first to explicitly address male preference for female throat color in threespine sticklebacks.Open Access Publishing Fun

The effects of traditional, superset, and tri-set resistance training structures on perceived intensity and physiological responses.

PURPOSE: Investigate the acute and short-term (i.e., 24 h) effects of traditional (TRAD), superset (SS), and tri-set (TRI) resistance training protocols on perceptions of intensity and physiological responses. METHODS: Fourteen male participants completed a familiarisation session and three resistance training protocols (i.e., TRAD, SS, and TRI) in a randomised-crossover design. Rating of perceived exertion, lactate concentration ([Lac]), creatine kinase concentration ([CK]), countermovement jump (CMJ), testosterone, and cortisol concentrations was measured pre, immediately, and 24-h post the resistance training sessions with magnitude-based inferences assessing changes/differences within/between protocols. RESULTS: TRI reported possible to almost certainly greater efficiency and rate of perceived exertion, although session perceived load was very likely lower. SS and TRI had very likely to almost certainly greater lactate responses during the protocols, with changes in [CK] being very likely and likely increased at 24 h, respectively. At 24-h post-training, CMJ variables in the TRAD protocol had returned to baseline; however, SS and TRI were still possibly to likely reduced. Possible increases in testosterone immediately post SS and TRI protocols were reported, with SS showing possible increases at 24-h post-training. TRAD and SS showed almost certain and likely decreases in cortisol immediately post, respectively, with TRAD reporting likely decreases at 24-h post-training. CONCLUSIONS: SS and TRI can enhance training efficiency and reduce training time. However, acute and short-term physiological responses differ between protocols. Athletes can utilise SS and TRI resistance training, but may require additional recovery post-training to minimise effects of fatigue

Seasonal pattern of peptic ulcer hospitalizations: analysis of the hospital discharge data of the Emilia-Romagna region of Italy

BACKGROUND: Previous studies have reported seasonal variation in peptic ulcer disease (PUD), but few large-scale, population-based studies have been conducted. METHODS: To verify whether a seasonal variation in cases of PUD (either complicated or not complicated) requiring acute hospitalization exists, we assessed the database of hospital admissions of the region Emilia Romagna (RER), Italy, obtained from the Center for Health Statistics, between January 1998 and December 2005. Admissions were categorized by sex, age ( or = 75 yrs), site of PUD lesion (stomach or duodenum), main complication (hemorrhage or perforation), and final outcome (intended as fatal outcome: in-hospital death; nonfatal outcome: patient discharged alive). Temporal patterns in PUD admissions were assessed in two ways, considering a) total counts per single month and season, and b) prevalence proportion, such as the monthly prevalence of PUD admissions divided by the monthly prevalence of total hospital admissions, to assess if the temporal patterns in the raw data might be the consequence of seasonal and annual variations in hospital admissions per se in the region. For statistical analysis, the chi2 test for goodness of fit and inferential chronobiologic method (Cosinor and partial Fourier series) were used. RESULTS: Of the total sample of PUD patients (26,848 [16,795 males, age 65 +/- 16 yrs; 10,053 females, age 72 +/- 15 yrs, p or = 75 yrs of age. There were more cases of duodenal (DU). (89.8%) than gastric ulcer (GU) (3.6%), and there were 1,290 (4.8%) fatal events. Data by season showed a statistically difference with the lowest proportion of PUD hospital admissions in summer (23.3%) (p < 0.001), for total cases and rather all subgroups. Chronobiological analysis identified three major peaks of PUD hospitalizations (September-October, January-February, and April-May) for the whole sample (p = 0.035), and several subgroups, with nadir in July. Finally, analysis of the monthly prevalence proportions yielded a significant (p = 0.025) biphasic pattern with a main peak in August-September-October, and a secondary one in January-February. CONCLUSIONS: A seasonal variation in PUD hospitalization, characterized by three peaks of higher incidence (Autumn, Winter, and Spring) is observed. When data corrected by monthly admission proportions are analyzed, late summer-autumn and winter are confirmed as higher risk periods. The underlying pathophysiologic mechanisms are unknown, and need further studies. In subjects at higher risk, certain periods of the year could deserve an appropriate pharmacological protection to reduce the risk of PUD hospitalization

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course