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It is well established that physical activity reduces all-cause mortality and can prolong life. Ultra-endurance running (UER) is an extreme sport that is becoming increasingly popular, and comprises running races above marathon distance, exceeding 6 h, and/or running fixed distances on multiple days. Serious acute adverse events are rare, but there is mounting evidence that UER may lead to long-term health problems. The purpose of this review is to present the current state of knowledge regarding the potential long-term health problems derived from UER, specifically potential maladaptation in key organ systems, including cardiovascular, respiratory, musculoskeletal, renal, immunological, gastrointestinal, neurological, and integumentary systems. Special consideration is given to youth, masters, and female athletes, all of whom may be more susceptible to certain long-term health issues. We present directions for future research into the pathophysiological mechanisms that underpin athlete susceptibility to long-term issues. Although all body systems can be affected by UER, one of the clearest effects of endurance exercise is on the cardiovascular system, including right ventricular dysfunction and potential increased risk of arrhythmias and hypertension. There is also evidence that rare cases of acute renal injury in UER could lead to progressive renal scarring and chronic kidney disease. There are limited data specific to female athletes, who may be at greater risk of certain UER-related health issues due to interactions between energy availability and sex-hormone concentrations. Indeed, failure to consider sex differences in the design of female-specific UER training programs may have a negative impact on athlete longevity. It is hoped that this review will inform risk stratification and stimulate further research about UER and the implications for long-term health.

Nausea and vomiting are common for runners during ultramarathons and often contribute to non-finishes. We aimed to determine the efficacy of ondansetron, a commonly used antiemetic, to treat nausea and vomiting in runners during an ultramarathon. Runners who had a previous history of frequent nausea or vomiting during races and entered in 160, 80, and 55 km ultramarathons in 2018 and 2019 were randomized in a double-blind fashion to 4 mg ondansetron or placebo capsules to use if they developed nausea or vomiting during the race with the ability to take three additional doses. Study participants completed a post-race online survey to assess medication use and efficacy. Of 62 study participants, 31 took either ondansetron (20) or placebo (11). In this small study, there were no group differences in those reporting any improvement in nausea and vomiting (p = 0.26) or in the amount of improvement (p = 0.15). We found no evidence that ondansetron capsules improve nausea and vomiting during ultramarathons.

PURPOSE This study assessed the prevalence of loneliness, burnout, and depressive symptoms from a national sample of family medicine physicians. DISCUSSION We conducted a cross-sectional survey of 401 physicians who were members of the American Academy of Family Physicians (AAFP) and AAFP National Research Network between December 7, 2019, and January 20, 2020. The study participants completed an anonymous, 30-item survey measuring loneliness, burnout, symptoms of depression, fatigue, in addition to providing demographic information. RESULTS The response rates were 16.3% (401 of 2456) for all the physicians, 7.0% (113 of 1606) for the AAFP NRN member physicians, and 33.9% (288 of 850) for the AAFP member insight physicians. The prevalence of loneliness, burnout, and depressive symptoms was 44.9% (165 of 367), 45.1% (181 of 401), and 44.3% (163 of 368) respectively. The physicians who experienced a greater feeling of loneliness compared with those who experienced a lesser feeling of loneliness were more likely to report at least 1 manifestation of burnout (69.1% vs 27.4%, P < .01), screen positive for depression (66.0% vs 27.6%, P < .01), and experience a higher degree of fatigue (59.5% vs 32.4%, P < .01). Depressive symptoms (odds ratio [OR] = 5.08; 95% confidence interval [CI], 4.64-7.94; P < .001), overwhelming exhaustion (OR = 7.19; 95% CI, 4.03 to 12.02; P < .001), and burnout (OR = 4.61; 95% CI, 2.96-7.19; P < .001) were associated with loneliness status. CONCLUSION Our findings demonstrate that loneliness is common in practicing family medicine physicians and is significantly associated with burnout and depression. Future work is needed to understand the various interactions and relationships among loneliness, burnout, and depression to help inform effective interventions.

Participation in ultramarathons continues to grow, especially among older individuals and among younger runners who may have less running and wilderness experience than many past participants. While ultramarathons tend to have relatively few serious medical issues, adverse medical incidents do occur. These factors make it increasingly important that appropriate safety precautions and medical support are defined and implemented at these events to enhance the safety of participants, spectators, and volunteers. This document establishes the minimum recommended level of medical support that should be available at ultramarathons based on current knowledge and the experience of the authors. It offers a balance that is intended to avoid excessive stress on the local medical system while also precluding undue burden on events to provide medical support beyond that which is practical. We propose a three-level classification system to define the extent of medical services, personnel, systems, supplies, and equipment in place and recommend the level of medical support based on event size, distance/duration, remoteness, and environmental conditions that may be encountered during the event. This document also outlines the recommended education and training of medical providers and discusses other medical and logistical considerations related to the provision of medical support at ultramarathons. We suggest that ultramarathon organizers review and adopt these recommendations to enhance safety and reduce the risk of adverse events to participants.

Medical coverage for mass sporting events, including marathons, ultramarathons, and triathlons, presents unique logistical challenges for the medical team. The medical director needs to work closely with the race director in understanding the particular challenges specific to the event. Because these events typically take place over a large geographic area, developing a clear communication plan within the medical team is crucial to ensure that proper care is being provided to the athletes. Preparation for these events also involves creating a race protocol specific to the event, communicating expectations with athletes, coordinating care with local emergency medicine services (EMS), recruiting and organizing medical staff, and providing medical supplies appropriate to the care required for the individual race.

A runner competing in a 100 mile trail race presented with severe lower chest pain and right upper abdominal pain. His pain started immediately after he took an over the counter non steroidal anti-inflammatory pill a few hundred metres after leaving the aid station. When he took the pill, he immediately had to vomit and spit out the pill. On arriving back at the aid station, he was noted to have severe left-sided chest pain that worsened with reclining. He also had profound dyspnoea. Initial vital signs were unremarkable. The runner was immediately transported to an emergency room and eventually found to have an oesophageal rupture. After surgical intervention and a lengthy recovery, the runner is back to participating in sport.

Turbulence definition is a challenge to physicists since beginning of studying of phenomena of turbulence which is not very well understood and is subject of active studies. Author is going to propose own definition of turbulence and compare it with existing ones. New definition is applied to some cases of fluids flows or known fluids parameter. Proposed definition helps better understand nature of turbulence and hopefully will boost more intense and focused efforts in turbulence study.

A modified process using inexpensive poison scavengers has been developed that allows for more economical and practical scale-up of metal-free catalytic hydrogenation. The scavengers remove impurities such as water and aldehydes that can hinder catalysis allowing for the use of commercial-grade solvents, substrates and gases. In addition, the scavengers have the unique ability to regenerate poisoned catalysts, allowing for increased turnover numbers and longer catalyst lifetimes. Hydrogenations of unpurified imine substrates proceed with high yield using a variety of metal-free hydrogenation catalysts, demonstrating the general compatibility of this process.

Objective (1) Compare rates of abnormal screening electrocardiograms (ECGs) using updated criteria compared with older criteria. (2) Compare rates of abnormal ECGs by ethnicity. (3) Evaluate ability of ECG criteria to detect the predicted number of athletes with previously undetected cardiovascular abnormalities. Design Prospective and retrospective review of ECGs. During the prospective portion of the study, the 2005 European Society of Cardiology criteria were used from 2008 to July 2011 and the 2011 Stanford criteria were used from August 2011 to 2013. Retrospectively, all ECGs were reevaluated using the 2011 Stanford criteria, 2013 Seattle criteria, and 2014 Sharma Refined criteria. Setting Division I National Collegiate Athletic Association University. Participants 874 incoming athletes over a 5-year period. Interventions ECG screening program. Main outcome measures Number of abnormal ECGs and number of athletes with newly discovered cardiac abnormalities. Results Abnormal ECG rates were the 2005 European criteria 10.7%, 2011 Stanford criteria 6.6%, 2013 Seattle criteria 2.8%, and 2014 Sharma Refined criteria 2.8%. In black athletes, the Stanford criteria resulted in more abnormal ECGs compared with Seattle or Sharma Refined. Three athletes were found to have a previously undetected cardiac abnormality (2 with hypertrophic cardiomyopathy and 1 with preexcitation). Conclusions More recent ECG screening criteria substantially reduce the abnormal ECG rate and thus the number of athletes requiring additional testing. ECG screening criteria identified the predicted number (1/300) of young athletes with serious underlying cardiovascular disease. These criteria prompt not only additional cardiovascular testing but also a more thorough cardiovascular history.

We have integrated two complementary methods, high-throughput virtual screening with a "high-content" wet screening technique based on frontal affinity chromatography with mass spectrometry detection (FAC-MS), for identification of hits against the erythropoietin-producing hepatocellular B2 (EphB2) receptor tyrosine kinase domain. Both an EphB2-directed virtual screen combining docking and scoring and a kinase-directed pharmacophore search strategy were used to identify a compound set enriched in bioactive compounds against EphB2. The coupling of virtual screening methodologies with FAC-MS is a unique hybrid approach that can be used to increase the efficacy of both hit discovery and optimization efforts in drug discovery and has successfully identified hits, in particular 19a (36% shift, IC(50) = 5.2 microM, K(d) = 3.3 microM), as inhibitors for EphB2, a potential cancer target.

FAC-MS offers a convenient method for measuring the relative binding strengths of ligands in a mixture and enables a rapid ranking and identification of ligands in the mixture as potential hits against immobilized targets. Using immobilized EphB2 receptor tyrosine kinase as the target and known kinase inhibitors, the results of FAC-MS screening (% shift) have been shown to correlate with the binding constant, K(d), and with IC(50) results from the more traditional ELISA assay. Therefore, since FAC-MS can accommodate a wide variety of target proteins, its applications could play a broad role in drug discovery not only at the hit discovery stage but also during the subsequent more rigorous screening at the hit-to-lead and lead optimization stages.

The global need for a pandemic influenza vaccine is large. High-income countries have stated their intent to provide universal access for pandemic influenza vaccine to their populations. Assuming that a two-dose schedule would be needed, providing universal coverage globally would represent approximately 6.5 billion two-dose courses or 13 billion doses. In the best case scenario, should an outbreak of pandemic influenza occur in the near term, using H5N1 as a proxy for the pandemic virus, the total available doses for the global population within six months of an out break would be only 1.2 billion courses or 2.4 billion doses. In addition, current stockpiles of pandemic influenza vaccine are limited. However, promising developments are occurring with respect to global capacity, technological innovation, and global conviction that offer potential solutions to the problem of pandemic influenza vaccine supply for the world’s population.

High-throughput screening (HTS) efforts to discover "hits" typically rely on the large-scale parallel screening of individual compounds with attempts to screen mixtures of compounds typically and, unfortunately, giving rise to false positives and false negatives due to the nature of the HTS readout (% inhibition/activation above a defined threshold) that makes deconvolution virtually intractable. Bioaffinity screening methods have emerged as an alternative or orthogonal method to classic HTS. One of these methods, frontal affinity chromatography coupled to mass spectrometry detection (FAC-MS), although still a relatively new technique, is turning out to be a viable screening tool. However, to push FAC-MS more to the forefront as a moderate primary HTS system (or a secondary screening assay), automation needs to be addressed. An automated FAC-MS system is described using 2 columns containing immobilized hERbeta, whereby while 1 column is being regenerated, the other is being used. The authors are extrapolating that in a continuous 24-h operation, the number of ligands screened could potentially approach 10,000. In addition, preliminary structure-activity relationship binding information (typically not seen in early primary HTS) can be obtained by observing the rank order of the library members in the various mixtures.

The emergence of a relatively new technique resulting from a combination of frontal affinity chromatography coupled with MS detection (FAC-MS) has extended the capabilities of MS in drug discovery and development. Its application in a broad range of biological systems, together with its label-free operation, relatively high throughput, ability to rank ligands and determine Kd, makes FAC-MS a universal tool enabling convenient and efficient screening in the identification of new potential drug leads. Here we will highlight FAC-MS screening studies and discuss where it can be applied in evaluating multiple protein-binding sites, protein-protein interactions and inactive proteins, and also in determining selectivity.

Methotrexate has been a clinical agent used in cancer, immunosuppression, rheumatoid arthritis, and other highly proliferative diseases for many years, yet its underlying molecular mechanism of action in these therapeutic areas is still unclear. We have previously reported using a chemical proteomics technique on several other potential pharmacodynamic targets of methotrexate. Here, using a frontal affinity chromatography with mass spectrometry detection, we confirm one of these targets, hypoxanthine-guanine amidophosphoribosyltransferase, as a true binder of methotrexate with a Kd of 4.2 μM. These results complement and confirm our recent study, but more importantly, shed light into the mechanism of action of methotrexate in oncology and other highly proliferative diseases and may help explain some unaccounted for effects of this drug. For example, despite the fact that DNA salvage pathway enzymes are highly active, methotrexate can be effective if it only targets enzymes of the de novo pathway.