Comparison of the ‘11+ Kids’ injury prevention programme and a regular warmup in children’s football (soccer) : a cost effectiveness analysis

Objective: To evaluate a potential reduction in injury related healthcare costs when using the '11+ Kids' injury prevention programme compared with a usual warmup in children's football. Methods: This cost effectiveness analysis was based on data collected in a cluster randomised controlled trial over one season from football teams (under-9 to under-13 age groups) in Switzerland. The intervention group (INT) replaced their usual warmup with '11+ Kids', while the control group (CON) warmed up as usual. Injuries, healthcare resource use and football exposure (in hours) were collected prospectively. We calculated the mean injury related costs in Swiss Francs (CHF) per 1000 hours of football. We calculated the cost effectiveness (the direct net healthcare costs divided by the net health effects of the '11+ Kids' intervention) based on the actual data in our study (trial based) and for a countrywide implementation scenario (model based). Results: Costs per 1000 hours of exposure were CHF228.34 (95% CI 137.45, 335.77) in the INT group and CHF469.00 (95% CI 273.30, 691.11) in the CON group. The cost difference per 1000 hours of exposure was CHF-240.66 (95% CI -406.89, -74.32). A countrywide implementation would reduce healthcare costs in Switzerland by CHF1.48 million per year. 1002 players with a mean age of 10.9 (SD 1.2) years participated. During 76 373 hours of football, 99 injuries occurred. Conclusion: The '11+ Kids' programme reduced the healthcare costs by 51% and was dominant (ie, the INT group had lower costs and a lower injury risk) compared with a usual warmup. This provides a compelling case for widespread implementation

Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPTRx) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPTRx. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPTRx or placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPTRx pharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPTRx and 12 to placebo. Adverse events were reported in 94% of MAPTRx-treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPTRx-treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPTRx groups. Clinicaltrials.gov registration number: NCT03186989

Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1 area: two modes of decreasing release probability

<p>Abstract</p> <p>Background</p> <p>Synaptic burst activation feeds back as a short-term depression of release probability at hippocampal CA3-CA1 synapses. This short-term synaptic plasticity requires functional astrocytes and it affects both the recently active (< 1 s) synapses (post-burst depression) as well as inactive neighboring synapses (transient heterosynaptic depression). The aim of this study was to investigate and compare the components contributing to the depression of release probability in these two different scenarios.</p> <p>Results</p> <p>When tested using paired-pulses, following a period of inactivity, the transient heterosynaptic depression was expressed as a reduction in the response to only the first pulse, whereas the response to the second pulse was unaffected. This selective depression of only the first response in a high-frequency burst was shared by the homosynaptic post-burst depression, but it was partially counteracted by augmentation at these recently active synapses. In addition, the expression of the homosynaptic post-burst depression included an astrocyte-mediated reduction of the pool of release-ready primed vesicles.</p> <p>Conclusions</p> <p>Our results suggest that activated astrocytes depress the release probability via two different mechanisms; by depression of vesicular release probability only at inactive synapses and by imposing a delay in the recovery of the primed pool of vesicles following depletion. These mechanisms restrict the expression of the astrocyte-mediated depression to temporal windows that are typical for synaptic burst activity.</p

Towards a Cross-Sectoral View of Nature-Based Solutions for Enabling Circular Cities

A framework developed by the COST Action Circular City (an EU-funded network of 500+ scientists from 40+ countries; COST = Cooperation in Science and Technology) for addressing Urban Circularity Challenges (UCCs) with nature-based solutions (NBSs) was analyzed by various urban sectors which refer to different fields of activities for circular management of resources in cities (i.e., reducing use of resources and production of waste). The urban sectors comprise the built environment, urban water management, resource recovery, and urban farming. We present main findings from sector analyses, discuss different sector perspectives, and show ways to overcome these differences. The results reveal the potential of NBSs to address multiple sectors, as well as multiple UCCs. While water has been identified as a key element when using NBSs in the urban environment, most NBSs are interconnected and also present secondary benefits for other resources. Using representative examples, we discuss how a holistic and systemic approach could facilitate the circular use of resources in cities. Currently, there is often a disciplinary focus on one resource when applying NBSs. The full potential of NBSs to address multifunctionality is, thus, usually not fully accounted for. On the basis of our results, we conclude that experts from various disciplines can engage in a cross-sectoral exchange and identify the full potential of NBSs to recover resources in circular cities and provide secondary benefits to improve the livelihood for locals. This is an important first step toward the full multifunctionality potential enabling of NBSs

The Response of Lactococcus lactis to Membrane Protein Production

Background: The biogenesis of membrane proteins is more complex than that of water-soluble proteins, and recombinant expression of membrane proteins in functional form and in amounts high enough for structural and functional studies is often problematic. To better engineer cells towards efficient protein production, we set out to understand and compare the cellular consequences of the overproduction of both classes of proteins in Lactococcus lactis, employing a combined proteomics and transcriptomics approach. Methodology and Findings: Highly overproduced and poorly expressed membrane proteins both resulted in severe growth defects, whereas amplified levels of a soluble substrate receptor had no effect. In addition, membrane protein overproduction evoked a general stress response (upregulation of various chaperones and proteases), which is probably due to accumulation of misfolded protein. Notably, upon the expression of membrane proteins a cell envelope stress response, controlled by the two-component regulatory CesSR system, was observed. Conclusions: The physiological response of L. lactis to the overproduction of several membrane proteins was determined and compared to that of a soluble protein, thus offering better understanding of the bottlenecks related to membrane protein production and valuable knowledge for subsequent strain engineering.

The Comparative Osteology of the Petrotympanic Complex (Ear Region) of Extant Baleen Whales (Cetacea: Mysticeti)

Anatomical comparisons of the ear region of baleen whales (Mysticeti) are provided through detailed osteological descriptions and high-resolution photographs of the petrotympanic complex (tympanic bulla and petrosal bone) of all extant species of mysticete cetaceans. Salient morphological features are illustrated and identified, including overall shape of the bulla, size of the conical process of the bulla, morphology of the promontorium, and the size and shape of the anterior process of the petrosal. We place our comparative osteological observations into a phylogenetic context in order to initiate an exploration into petrotympanic evolution within Mysticeti.The morphology of the petrotympanic complex is diagnostic for individual species of baleen whale (e.g., sigmoid and conical processes positioned at midline of bulla in Balaenoptera musculus; confluence of fenestra cochleae and perilymphatic foramen in Eschrichtius robustus), and several mysticete clades are united by derived characteristics. Balaenids and neobalaenids share derived features of the bulla, such as a rhomboid shape and a reduced anterior lobe (swelling) in ventral aspect, and eschrichtiids share derived morphologies of the petrosal with balaenopterids, including loss of a medial promontory groove and dorsomedial elongation of the promontorium. Monophyly of Balaenoidea (Balaenidae and Neobalaenidae) and Balaenopteroidea (Balaenopteridae and Eschrichtiidae) was recovered in phylogenetic analyses utilizing data exclusively from the petrotympanic complex.This study fills a major gap in our knowledge of the complex structures of the mysticete petrotympanic complex, which is an important anatomical region for the interpretation of the evolutionary history of mammals. In addition, we introduce a novel body of phylogenetically informative characters from the ear region of mysticetes. Our detailed anatomical descriptions, illustrations, and comparisons provide valuable data for current and future studies on the phylogenetic relationships, evolution, and auditory physiology of mysticetes and other cetaceans throughout Earth's history