Are different groups of patients with stroke more likely to be excluded from the new UK general medical services contract? A cross-sectional retrospective analysis of a large primary care population

Peer reviewedPublisher PD

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care

Autoregulation in resistance training : addressing the inconsistencies

Autoregulation is a process that is used to manipulate training based primarily on the measurement of an individual's performance or their perceived capability to perform. Despite being established as a training framework since the 1940s, there has been limited systematic research investigating its broad utility. Instead, researchers have focused on disparate practices that can be considered specific examples of the broader autoregulation training framework. A primary limitation of previous research includes inconsistent use of key terminology (e.g., adaptation, readiness, fatigue, and response) and associated ambiguity of how to implement different autoregulation strategies. Crucially, this ambiguity in terminology and failure to provide a holistic overview of autoregulation limits the synthesis of existing research findings and their dissemination to practitioners working in both performance and health contexts. Therefore, the purpose of the current review was threefold: first, we provide a broad overview of various autoregulation strategies and their development in both research and practice whilst highlighting the inconsistencies in definitions and terminology that currently exist. Second, we present an overarching conceptual framework that can be used to generate operational definitions and contextualise autoregulation within broader training theory. Finally, we show how previous definitions of autoregulation fit within the proposed framework and provide specific examples of how common practices may be viewed, highlighting their individual subtleties

Effect of a single acupuncture treatment on surgical wound healing in dogs: a randomized, single blinded, controlled pilot study

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to investigate the effect of acupuncture on wound healing after soft tissue or orthopaedic surgery in dogs.</p> <p>Methods</p> <p>29 dogs were submitted to soft tissue and/or orthopaedic surgeries. Five dogs had two surgical wounds each, so there were totally 34 wounds in the study. All owners received instructions for post operative care as well as antibiotic and pain treatment. The dogs were randomly assigned to treatment or control groups. Treated dogs received one dry needle acupuncture treatment right after surgery and the control group received no such treatment. A veterinary surgeon that was blinded to the treatment, evaluated the wounds at three and seven days after surgery in regard to oedema (scale 0-3), scabs (yes/no), exudate (yes/no), hematoma (yes/no), dermatitis (yes/no), and aspect of the wound (dry/humid).</p> <p>Results</p> <p>There was no significant difference between the treatment and control groups in the variables evaluated three and seven days after surgery. However, oedema reduced significantly in the group treated with acupuncture at seven days compared to three days after surgery, possibly due the fact that there was more oedema in the treatment group at day three (although this difference was nor significant between groups).</p> <p>Conclusions</p> <p>The use of a single acupuncture treatment right after surgery in dogs did not appear to have any beneficial effects in surgical wound healing.</p

Disparity Changes in 370 Ma Devonian Fossils: The Signature of Ecological Dynamics?

Early periods in Earth's history have seen a progressive increase in complexity of the ecosystems, but also dramatic crises decimating the biosphere. Such patterns are usually considered as large-scale changes among supra-specific groups, including morphological novelties, radiation, and extinctions. Nevertheless, in the same time, each species evolved by the way of micro-evolutionary processes, extended over millions of years into the evolution of lineages. How these two evolutionary scales interacted is a challenging issue because this requires bridging a gap between scales of observation and processes. The present study aims at transferring a typical macro-evolutionary approach, namely disparity analysis, to the study of fine-scale evolutionary variations in order to decipher what processes actually drove the dynamics of diversity at a micro-evolutionary level. The Late Frasnian to Late Famennian period was selected because it is punctuated by two major macro-evolutionary crises, as well as a progressive diversification of marine ecosystem. Disparity was estimated through this period on conodonts, tooth-like fossil remains of small eel-like predators that were part of the nektonic fauna. The study was focused on the emblematic genus of the period, Palmatolepis. Strikingly, both crises affected an already impoverished Palmatolepis disparity, increasing risks of random extinction. The major disparity signal rather emerged as a cycle of increase and decrease in disparity during the inter-crises period. The diversification shortly followed the first crisis and might correspond to an opportunistic occupation of empty ecological niche. The subsequent oriented shrinking in the morphospace occupation suggests that the ecological space available to Palmatolepis decreased through time, due to a combination of factors: deteriorating climate, expansion of competitors and predators. Disparity changes of Palmatolepis thus reflect changes in the structure of the ecological space itself, which was prone to evolve during this ancient period where modern ecosystems were progressively shaped

A New (Old), Invasive Ant in the Hardwood Forests of Eastern North America and Its Potentially Widespread Impacts

Biological invasions represent a serious threat for the conservation of biodiversity in many ecosystems. While many social insect species and in particular ant species have been introduced outside their native ranges, few species have been successful at invading temperate forests. In this study, we document for the first time the relationship between the abundance of the introduced ant, Pachycondyla chinensis, in mature forests of North Carolina and the composition, abundance and diversity of native ant species using both a matched pair approach and generalized linear models. Where present, P. chinensis was more abundant than all native species combined. The diversity and abundance of native ants in general and many individual species were negatively associated with the presence and abundance of P. chinensis. These patterns held regardless of our statistical approach and across spatial scales. Interestingly, while the majority of ant species was strongly and negatively correlated with the abundance and presence of P. chinensis, a small subset of ant species larger than P. chinensis was either as abundant or even more abundant in invaded than in uninvaded sites. The large geographic range of this ant species combined with its apparent impact on native species make it likely to have cascading consequences on eastern forests in years to come, effects mediated by the specifics of its life history which is very different from those of other invasive ants. The apparent ecological impacts of P. chinensis are in addition to public health concerns associated with this species due to its sometimes, deadly sting

The Prosensory Function of Sox2 in the Chicken Inner Ear Relies on the Direct Regulation of Atoh1

The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to explore the regulation of Atoh1 by Sox2. The results show that hair cells derive from Sox2-positive otic progenitors and that Sox2 directly activates Atoh1 through a transcriptional activator function that requires the integrity of Sox2 DNA binding domain. Atoh1 activation depends on Sox transcription factor binding sites (SoxTFBS) present in the Atoh1 3′ enhancer where Sox2 directly binds, as shown by site directed mutagenesis and chromatin immunoprecipitation (ChIP). In the inner ear, Atoh1 enhancer activity is detected in the neurosensory domain and it depends on Sox2. Dominant negative competition (Sox2HMG-Engrailed) and mutation of the SoxTFBS abolish the reporter activity in vivo. Moreover, ChIP assay in isolated otic vesicles shows that Sox2 is bound to the Atoh1 enhancer in vivo. However, besides activating Atoh1, Sox2 also promotes the expression of Atoh1 negative regulators and the temporal profile of Atoh1 activation by Sox2 is transient suggesting that Sox2 triggers an incoherent feed-forward loop. These results provide a mechanism for the prosensory function of Sox2 in the inner ear. We suggest that sensory competence is established early in otic development through the activation of Atoh1 by Sox2, however, hair cell differentiation is prevented until later stages by the parallel activation of negative regulators of Atoh1 function

Free energies of binding of R- and S-propranolol to wild-type and F483A mutant cytochrome P450 2D6 from molecular dynamics simulations

Detailed molecular dynamics (MD) simulations have been performed to reproduce and rationalize the experimental finding that the F483A mutant of CYP2D6 has lower affinity for R-propranolol than for S-propranolol. Wild-type (WT) CYP2D6 does not show this stereospecificity. Four different approaches to calculate the free energy differences have been investigated and were compared to the experimental binding data. From the differences between calculations based on forward and backward processes and the closure of thermodynamic cycles, it was clear that not all simulations converged sufficiently. The approach that calculates the free energies of exchanging R-propranolol with S-propranolol in the F483A mutant relative to the exchange free energy in WT CYP2D6 accurately reproduced the experimental binding data. Careful inspection of the end-points of the MD simulations involved in this approach, allowed for a molecular interpretation of the observed differences

Development and validation of a model to predict the 10-year risk of general practitioner-recorded COPD

There is increasing interest in the earlier detection of, and intervention in, patients at highest risk of developing chronic obstructive pulmonary disease (COPD).status: publishe