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European foulbrood (EFB) is a severe bacterial disease of honey bee brood often leading to significant declines in colony health and honey production. The dearth of data on this disease in the United States (US) complicates response efforts. In 2021 and 2022 we conducted a two-year cross-sectional surveillance study among Michigan beekeepers to establish baseline pathogen and disease prevalence. We combined this surveillance with molecular epidemiology to investigate genetic diversity, and transmission dynamics of Melissococcus plutonius , the causative agent of EFB, in US honey bee colonies. PCR screening detected M. plutonius in all 15 migratory and stationary beekeeping operations and in 6 of 14 hobby beekeeping operations. Infection and disease were found to be seasonal, with prevalence of both peaking in June when over half the colonies were infected, and over 20% had clinical EFB. Whole genome, single nucleotide polymorphism analysis revealed wide genetic diversity even within a single hive. Operations often had multiple genotypes present which varied from year to year, consistent with high rates of transmission and reinfection. Prevalence and whole genome data provided here will be critical in tracking the efficacy of mitigation efforts and underscore the necessity of additional epidemiological investigations.

This randomized trial showed no benefit of the addition of arthroscopic treatment to optimized physical and medical therapy and provided evidence that arthroscopic surgery is not indicated for the treatment of osteoarthritis of the knee. This trial showed no benefit of the addition of arthroscopic treatment to optimized physical and medical therapy and provided evidence that arthroscopic surgery is not indicated for the treatment of osteoarthritis of the knee. Osteoarthritis of the knee is a degenerative disease that causes joint pain, stiffness, and decreased function. 1 – 3 Treatment is multidisciplinary and involves physical therapy, medication, and surgery. Arthroscopic surgery, in which an arthroscope is inserted into the knee joint, allows for lavage, a procedure that removes particulate material such as cartilage fragments and calcium crystals. It also allows for débridement, whereby articular surfaces and osteophytes can be surgically smoothed. The goal of this procedure is to reduce synovitis and eliminate mechanical interference with joint motion. Although arthroscopic surgery has been widely used for osteoarthritis of the knee, scientific evidence to . . .

Gliomas have displayed significant challenges in oncology due to their high degree of invasiveness, recurrence, and resistance to treatment strategies. In this work, the key hub genes mainly associated with different grades of glioma, which were represented by pilocytic astrocytoma (PA), oligodendroglioma (OG), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM), were identified through weighted gene co-expression network analysis (WGCNA) of microarray datasets retrieved from the Gene Expression Omnibus (GEO) database. Through this, four highly correlated modules were observed to be present across the PA (GSE50161), OG (GSE4290), AA (GSE43378), and GBM (GSE36245) datasets. The functional annotation and pathway enrichment analysis done through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that the modules and hub genes identified were mainly involved in signal transduction, transcription regulation, and protein binding, which collectively deregulate several signaling pathways, mainly PI3K/Akt and metabolic pathways. The involvement of several hub genes primarily linked to other signaling pathways, including the cAMP, MAPK/ERK, Wnt/β-catenin, and calcium signaling pathways, indicates potential interconnectivity and influence on the PI3K/Akt pathway and, subsequently, glioma severity. The Drug Repurposing Encyclopedia (DRE) was used to screen for potential drugs based on the up- and downregulated hub genes, wherein the synthetic progestin hormones norgestimate and ethisterone were the top drug candidates. This shows the potential neuroprotective effect of progesterone against glioma due to its influence on EGFR expression and other signaling pathways. Aside from these, several experimental and approved drug candidates were also identified, which include an adrenergic receptor antagonist, a PPAR-γ receptor agonist, a CDK inhibitor, a sodium channel blocker, a bradykinin receptor antagonist, and a dopamine receptor agonist, which further highlights the gene network as a potential therapeutic avenue for glioma.

An important aim of high tibial osteotomy (HTO) is to prevent or delay the need for total knee replacement (TKR). We sought to estimate the frequency and timing of conversion from HTO to TKR and the factors associated with it. We prospectively evaluated patients with osteoarthritis (OA) of the knee who underwent medial opening wedge HTO from 2002 to 2014 and analyzed the cumulative incidence of TKR in July 2019. The presence or absence of TKR on the HTO limb was identified from the orthopedic surgery reports and knee radiographs contained in the electronic medical records for each patient at London Health Sciences Centre. We used cumulative incidence curves to evaluate the primary outcome of time to TKR. We used multivariable Cox proportional hazards analysis to assess potential preoperative predictors including radiographic disease severity, malalignment, correction size, pain, sex, age, body mass index (BMI) and year of surgery. Among 556 patients who underwent 643 HTO procedures, the cumulative incidence of TKR was 5% (95% confidence interval [CI] 3%–7%) at 5 years and 21% (95% CI 17%–26%) at 10 years. With the Cox proportional hazards multivariable model, the following preoperative factors were significantly associated with an increased rate of conversion: radiographic OA severity (adjusted hazard ratio [HR] 1.96, 95% CI 1.12–3.45), pain (adjusted HR 0.85, 95% CI 0.75–0.96)], female sex (adjusted HR 1.67, 95% CI 1.08–2.58), age (adjusted HR 1.50 per 10 yr, 95% CI 1.17–1.93) and BMI (adjusted HR 1.31 per 5 kng/m2, 95% CI 1.12–1.53). We found that 79% of knees did not undergo TKR within 10 years after undergoing medial opening wedge HTO. The strongest predictor of conversion to TKR is greater radiographic disease at the time of HTO.

Athletes are increasingly required to travel domestically and internationally, often resulting in travel fatigue and jet lag. Despite considerable agreement that travel fatigue and jet lag can be a real and impactful issue for athletes regarding performance and risk of illness and injury, evidence on optimal assessment and management is lacking. Therefore 26 researchers and/or clinicians with knowledge in travel fatigue, jet lag and sleep in the sports setting, formed an expert panel to formalise a review and consensus document. This manuscript includes definitions of terminology commonly used in the field of circadian physiology, outlines basic information on the human circadian system and how it is affected by time-givers, discusses the causes and consequences of travel fatigue and jet lag, and provides consensus on recommendations for managing travel fatigue and jet lag in athletes. The lack of evidence restricts the strength of recommendations that are possible but the consensus group identified the fundamental principles and interventions to consider for both the assessment and management of travel fatigue and jet lag. These are summarised in travel toolboxes including strategies for pre-flight, during flight and post-flight. The consensus group also outlined specific steps to advance theory and practice in these areas.

The primary aims of the present study were to assess the sleep hygiene knowledge of high performance team sport coaches and sports science support staff; the sleep practices these individuals implement with athletes; and the barriers to the more frequent use of these practices. Cross-sectional observational study. A sample of 86 Australian coaches and sports science support staff working within high performance team sport volunteered to complete a four-part questionnaire, including the Sleep Beliefs Survey used to assess sleep hygiene knowledge. Overall sleep hygiene knowledge was adequate (15.3±2.9, score range 0–20; mean±SD), however knowledge of sleep–wake cycle behaviours (score 4.9±1.6 out of 7) and thoughts and attitudes about sleep (3.6±1.0 out of 5) were inadequate. Over half (56%) of coaches and support staff had monitored athlete sleep, while 43% had promoted sleep hygiene. Lack of resources (response range 44–60%) and knowledge (16–41%) were the two main barriers to the implementation of sleep monitoring and sleep hygiene practices. Team sport coaches and sports science support staff have adequate overall sleep hygiene knowledge, yet some specific areas (e.g. sleep–wake cycle behaviours) warrant improvement. There appear to be limited sleep practices implemented with athletes, particularly regarding the promotion of sleep hygiene. The development of educational sleep resources for coaches and support staff to implement with athletes may help address the identified barriers and improve sleep knowledge.

With the recent growth in female sport, practitioners need to be able to provide specific support to female athletes to ensure their sleep, health and athletic performance are optimised. Examine the patterns, duration and quality of sleep among elite female athletes, and consider the impact of situational challenges and their effects on the sleep of elite female athletes. Data was located through a search of SPORTDiscus, MEDLINE and Scopus from inception up to May 2021. Studies needed to be peer-reviewed research reporting quantitative sleep outcomes for female athletes ≥ 18 years of age and competing at a predefined elite level. A meta-analysis was performed on habitual sleep outcomes (e.g. total sleep time [TST] and sleep efficiency [SE]) measured with actigraphy. A total of 38 studies were included. Meta-analysis showed habitual TST (n = 14) was 7.8 h [7.4, 8.2] (mean [95% CI]), and SE was 86.7% [84.7, 88.6], with high variability among studies (I = 97.8-98.2%). Subjective sleep complaints are common before a competition, as do post-training sleep disturbances (63% studies report TST decrease), and post-competition sleep disturbances (75% studies report TST decrease). Female athletes achieve satisfactory objective sleep quantity and quality during habitual periods, but experience sleep disturbances pre- and post-situational challenges. There is high variability of objective sleep outcomes, demonstrating the individual nature of habitual female athlete sleep. Overall, future research must focus on optimising the sleep appraisal methods and creating high-quality study designs in a broader number of sports.

Describe the effects of eastward long-haul transmeridian air travel on subjective jet-lag, sleep and wellness in professional football (soccer) players prior to the 2014 FIFA World Cup in Brazil. Single cohort involving twenty-two male professional football players representing a national football team. Data was collected from players prior to and following international travel from Sydney, Australia to Vitoria, Brazil. In total there were three flights, 19-h and 14,695km of travel east across 11 time-zones. Training load and wellness measures were obtained in the week prior to and following travel, whilst sleep and jet-lag measures were collected on the day prior to travel (Pre), the day of arrival and for five days following travel (Post 1–5). Compared to Pre, perceived jet-lag was significantly increased on Post 1 to 4, with significantly greater levels on Post 1 compared to Post 5 (p<0.05). Self-reported sleep duration during travel was 5.9 (4.8–7.0) h, which was significantly lower than all other nights (p˂0.01), except for the night of arrival, where time in bed and sleep duration were significantly reduced compared to Post 1–4 (p˂0.01). Lastly, compared to the week prior to travel, mean wellness was significantly reduced during the week following travel (p˂0.01). Self-reported sleep disruption during and following eastward long-haul transmeridian air travel, together with exacerbated jet-lag symptoms may result in reduced player wellness. Consequently, player preparedness for subsequent training and competition may be impeded, though physical performance data is lacking.

Animal venom has been gaining traction as a potential source of therapeutics for various diseases. Spiders encompass a wide variety of venom-producing species, of which tarantulas of the family Theraphosidae are widely known across the globe. Research towards tarantula venom therapeutics has led to its potential application as antinociceptives. Death receptors are cellular receptors that induce apoptosis—the body’s natural suicide mechanism—to destroy malfunctioning cells. These are particularly of interest in cancer research, as this mechanism is tampered with, resulting in cancer cell proliferation. In this study, the viability of venom toxins from the Theraphosidae family of spiders to induce apoptosis by binding to human death receptors is investigated by carrying out anti-cancer screening, molecular docking, ADMET evaluation, then molecular dynamics and thermodynamic analysis twice, first to ascertain the best receptor–peptide systems per receptor, and secondly to more comprehensively describe binding stability and thermodynamics. Results point to favorable receptor–peptide interactions due to similarities in equilibrium behavior with the death ligand–death receptor systems, along with favorable end-state binding energies and ADMET analysis results. Further inquiry is recommended to assess the real-life efficacy and viability of theraphotoxins as apoptosis therapeutics and further improve on their ability to induce apoptosis.

Background/Objectives: The molecular heterogeneity and metabolic flexibility of Hepatocellular Carcinoma (HCC) pose significant challenges to the efficacy of systemic therapy for advanced cases. Early screening difficulties often delay diagnosis, leading to more advanced stages at presentation. Combined with the inconsistent responses to current systemic therapies, HCC continues to have one of the highest mortality rates among cancers. Thus, this paper seeks to contribute to the development of systemic therapy options through the consideration of HCC’s metabolic vulnerabilities and lay the groundwork for future in vitro studies. Methods: Transcriptomic data were used to calculate single and double knockout options for HCC using genetic Minimal Cut Sets. Furthermore, using QSAR modeling, drug repositioning opportunities were assessed to inhibit the selected genes. Results: Two single knockout options that were also annotated as essential pairs were found within the pyrimidine metabolism pathway of HCC, wherein the knockout of either DHODH or TYMS is potentially disruptive to proliferation. The result of the flux balance analysis and gene knockout simulation indicated a significant decrease in biomass production. Three machine learning algorithms were assessed for their performance in predicting the pIC50 of a given compound for the selected genes. SVM-rbf performed the best on unseen data achieving an R2 of 0.82 for DHODH and 0.81 for TYMS. For DHODH, the drugs Oteseconazole, Tipranavir, and Lusutrombopag were identified as potential inhibitors. For TYMS, the drugs Tadalafil, Dabigatran, Baloxavir Marboxil, and Candesartan Cilexetil showed promise as inhibitors. Conclusions: Overall, this study suggests in vitro testing of the identified drugs to assess their capabilities in inducing pyrimidine starvation on HCC.