Effects of Recreational Ski Mountaineering on Cumulative Muscle Fatigue – A Longitudinal Trial

Sport is known to have many positive effects on mental and physical health. High-intensity exercise is considered to decrease muscle strength and induce muscle fatigue, which is associated with a higher risk of injury. In recreational alpine skiers, a decrease of eccentric peak hamstring torque, as an indication of muscle fatigue, occurs even after 1 day of skiing. The popularity of ski mountaineering is increasing enormously, but no studies are available on its effects on muscle strength. Therefore, the present study examined the consequences of ski mountaineering on muscle fatigue of the concentric/eccentric quadriceps and/or hamstrings. In addition, a possible role of myofascial foam rolling in reducing muscle fatigue was evaluated. Fifty recreational ski mountaineers (27 males, 23 females) completed five consecutive tours of ski mountaineering within 1 week. After each day of skiing, participants underwent an isokinetic muscle test assessing the concentric and eccentric muscle strength of both thighs. One group completed an additional session of myofascial foam rolling. Right and left concentric quadriceps peak torque, left hamstrings peak torque, left eccentric quadriceps peak torque, as well as right and left hamstring peak torque, were reduced after a single day of ski mountaineering (p ≤ 0.016 for all). However, no cumulative muscle fatigue was detected and we could not demonstrate any effect of myofascial foam rolling. The results show conclusively that a single day of ski mountaineering leads to a significant decrease of concentric and eccentric quadriceps and hamstring strength. Therefore, in order to improve muscle strength for the ski mountaineering season, a physical training program including concentric and eccentric methods can be recommended

In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

Diabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP-PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention

Agent-based simulations for protecting nursing homes with prevention and vaccination strategies

Due to its high lethality amongst the elderly, the safety of nursing homes has been of central importance during the COVID-19 pandemic. With test procedures becoming available at scale, such as antigen or RT-LAMP tests, and increasing availability of vaccinations, nursing homes might be able to safely relax prohibitory measures while controlling the spread of infections (meaning an average of one or less secondary infections per index case). Here, we develop a detailed agent-based epidemiological model for the spread of SARS-CoV-2 in nursing homes to identify optimal prevention strategies. The model is microscopically calibrated to high-resolution data from nursing homes in Austria, including detailed social contact networks and information on past outbreaks. We find that the effectiveness of mitigation testing depends critically on the timespan between test and test result, the detection threshold of the viral load for the test to give a positive result, and the screening frequencies of residents and employees. Under realistic conditions and in absence of an effective vaccine, we find that preventive screening of employees only might be sufficient to control outbreaks in nursing homes, provided that turnover times and detection thresholds of the tests are low enough. If vaccines that are moderately effective against infection and transmission are available, control is achieved if 80% or more of the inhabitants are vaccinated, even if no preventive testing is in place and residents are allowed to have visitors. Since these results strongly depend on vaccine efficacy against infection, retention of testing infrastructures, regular voluntary screening and sequencing of virus genomes is advised to enable early identification of new variants of concern.Comment: Supplementary material is included in the manuscript PD

4-Hydroxy-1-naphthaldehydes: proton transfer or deprotonation

A series of naphthaldehydes, including a Mannich base, have been investigated by UV-Vis spectroscopy, NMR and theoretical methods to explore their potential tautomerism. In the case of 4-hydroxy-1-naphthaldehyde concentration dependent deprotonation has been detected in methanol and acetonitrile. For 4-hydroxy-3-(piperidin-1-ylmethyl)-1-naphthaldehyde (a Mannich base) an intramolecular proton transfer involving the OH group and the piperidine nitrogen occurs. In acetonitrile the equilibrium is predominantly at the OH-form, whereas in methanol the proton transferred tautomer is the preferred form. In chloroform and toluene, the OH form is completely dominant. Both 4-hydroxy-1-naphthaldehyde and 4-methoxy-1-naphthaldehyde (fixed enol form) show dimerization in the investigated solvents and the crystallographic data, obtained for the latter, confirm the existence of a cyclic dimer

Staphylococcus aureus Induces Eosinophil Cell Death Mediated by α-hemolysin

Staphylococcus aureus, a major human pathogen, exacerbates allergic disorders, including atopic dermatitis, nasal polyps and asthma, which are characterized by tissue eosinophilia. Eosinophils, via their destructive granule contents, can cause significant tissue damage, resulting in inflammation and further recruitment of inflammatory cells. We hypothesised that the relationship between S. aureus and eosinophils may contribute to disease pathology. We found that supernatants from S. aureus (SH1000 strain) cultures cause rapid and profound eosinophil necrosis, resulting in dramatic cell loss within 2 hours. This is in marked contrast to neutrophil granulocytes where no significant cell death was observed (at equivalent dilutions). Supernatants prepared from a strain deficient in the accessory gene regulator (agr) that produces reduced levels of many important virulence factors, including the abundantly produced α-hemolysin (Hla), failed to induce eosinophil death. The role of Hla in mediating eosinophil death was investigated using both an Hla deficient SH1000-modified strain, which did not induce eosinophil death, and purified Hla, which induced concentration-dependent eosinophil death via both apoptosis and necrosis. We conclude that S. aureus Hla induces aberrant eosinophil cell death in vitro and that this may increase tissue injury in allergic disease

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Medical services at the first Winter Youth Olympic Games 2012 in Innsbruck/Austria

The Youth Olympic Games (YOG) are a new format designed by the International Olympic Committee. So far no reference data are available regarding the organisation or implementation of the medical services that were needed for the Winter Youth Olympic Games that took place for the first time in Innsbruck 9–24 January 2012. Conclusions: Medical service coverage at the first Winter Youth Olympic Games seemed to be appropriate. No disaster or epidemic disease challenged the medical service plan. Future organising committees could use the provided data as a reference for their planning efforts

Regional differences in spatiotemporal drought characteristics in Great Britain

Despite being one of the most damaging natural hazards, droughts and their spatiotemporal dynamics are typically not well understood. Great Britain, which is the focus of this work, has experienced many major drought episodes in the past, causing a range of socioeconomic and environmental impacts. Here, we apply a recently developed technique to identify and characterise past droughts, using space-time connectivity to extract events from a monthly gridded precipitation dataset covering 1862–2015, without imposing fixed geographical boundaries or time-frames. For each grid cell, the data was aggregated into four new time series using moving averages over 3-, 6-, 12- and 24-month windows. These reflect a range of response times for different types of drought impacts. Drought events were then extracted for each time window separately. In order to assess regional differences in drought characteristics, each extracted drought was assigned to one of three regions: the South-East (SE), the North-West (NW) and a “Transition” region in-between them. A frequency analysis of drought characteristics (duration, area, intensity and severity) highlighted differences between regions: for short and medium accumulation periods (3, 6, and 12 months), short and less severe droughts are more frequent in the NW than in the SE, whereas long, spatially extended and more severe droughts are more frequent in the SE than in the NW. However, for long accumulation periods (24 months), fewer differences are observed between the NW and the SE. In the “Transition” region, severe droughts are less frequent than in the other two regions. A timeline of historic drought events detected by our method included the vast majority of known drought events from previous studies, with a few additional ones, and we shed important new light on the relative severity of these historical drought episodes. Finally, an analysis of the spatial coherence between regions showed that the most extreme drought events presented little spatial coherence, whereas less severe droughts tend to be more spatially coherent. This has important implications for water resources planning and drought management strategies, particularly given the increasing emphasis on inter-regional water transfers as a potential solution in situations of extreme drought