RESUMEN
Transient acute kidney injury (AKI) following ultraendurance footraces is a common biochemical diagnosis. However, severe AKI requiring renal replacement therapy is uncommon in ultramarathoners. We report 4 runners (3 men; mean age, 44 ± 3 y) who required prolonged (10-42 d) dialysis following the Western States 100 Mile Endurance Run over a 3-y span (0.38% of starters). The maximum ambient temperatures on the race day ranged from 36.6° to 38.3°C. The runners presented to local hospitals 17 to 32 h after running, with laboratories confirming rhabdomyolysis, hyponatremia (mean serum sodium concentration, 127±2 mmolâ L-1), and AKI (mean serum creatinine concentration, 8.5±2 mgâ dL-1). The case-cluster report highlights the potential synergistic effects of high ambient temperatures, muscle damage, and electrolyte imbalance on protracted renal dysfunction in ultramarathoners competing in a warming world.
Asunto(s)
Lesión Renal Aguda , Hiponatremia , Carrera , Masculino , Humanos , Adulto , Persona de Mediana Edad , Diálisis Renal , Sodio , Carrera/fisiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , CreatininaAsunto(s)
Carrera , Humanos , Estado Nutricional , Resistencia Física/fisiología , Carrera/fisiologíaRESUMEN
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.
Asunto(s)
Carrera , Adolescente , Arritmias Cardíacas , Atletas , Femenino , Humanos , Masculino , Carrera de Maratón , Estado Nutricional , Resistencia Física/fisiología , Carrera/fisiologíaRESUMEN
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.
Asunto(s)
Agotamiento Profesional , Distrés Psicológico , Agotamiento Profesional/epidemiología , Agotamiento Psicológico , Estudios Transversales , Depresión/diagnóstico , Depresión/epidemiología , Medicina Familiar y Comunitaria , Humanos , Soledad , Médicos de Familia , Encuestas y CuestionariosRESUMEN
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.
RESUMEN
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.
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Atención a la Salud/organización & administración , Carrera de Maratón , Medicina Deportiva/organización & administración , HumanosRESUMEN
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.
Asunto(s)
Dolor en el Pecho/etiología , Perforación del Esófago/diagnóstico , Enfermedades del Mediastino/diagnóstico , Adulto , Atletas , Broncoscopía , Diagnóstico Diferencial , Perforación del Esófago/complicaciones , Perforación del Esófago/cirugía , Humanos , Masculino , Enfermedades del Mediastino/complicaciones , Enfermedades del Mediastino/cirugía , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/etiología , Enfisema Mediastínico/terapia , CarreraRESUMEN
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.
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Atletas/estadística & datos numéricos , Anomalías Cardiovasculares/diagnóstico , Electrocardiografía , Tamizaje Masivo , Adolescente , Adulto , Anomalías Cardiovasculares/epidemiología , Electrocardiografía/normas , Femenino , Humanos , Masculino , Tamizaje Masivo/normas , Estudios Prospectivos , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Although eye pain is often accompanied by redness or injection, pain can also occur with a quiet eye. Pain in a quiet eye can be the first sign of a vision-threatening condition, a more benign ophthalmologic condition, or a nonophthalmologic condition. Acute narrow-angle glaucoma is an emergent vision-threatening condition that requires immediate treatment and referral to an ophthalmologist. Although most nonophthalmologic conditions that cause eye pain do not need immediate treatment, giant cell (temporal) arteritis requires urgent treatment with corticosteroids. Other vascular conditions, such as carotid artery disease, thrombosis of the cavernous sinus, and transient ischemic attack or stroke, rarely cause eye pain but must be considered. Pain may also be referred from the sinuses or from neurologic conditions, such as trigeminal neuralgia, migraine and cluster headaches, and increased intracranial pressure. The differential diagnosis of eye pain in the quiet eye is extensive, necessitating a systematic and thorough approach.
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Oftalmopatías/complicaciones , Oftalmopatías/diagnóstico , Dolor/etiología , HumanosRESUMEN
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.
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Brotes de Enfermedades/prevención & control , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Humanos , Vacunas contra la Influenza/economía , Vacunas contra la Influenza/provisión & distribución , VacunaciónRESUMEN
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.
Asunto(s)
Cromatografía de Afinidad/métodos , Receptor beta de Estrógeno/metabolismo , Espectrometría de Masas/métodos , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Automatización , Cromatografía de Afinidad/instrumentación , Receptor beta de Estrógeno/química , Receptor beta de Estrógeno/genética , Histidina/química , Humanos , Ligandos , Espectrometría de Masas/instrumentación , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Serina/metabolismoRESUMEN
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.
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Cromatografía de Afinidad , Diseño de Fármacos , Evaluación Preclínica de Medicamentos/métodos , Espectrometría de Masas , Proteínas/química , Sitios de Unión , Ligandos , Modelos Moleculares , Conformación MolecularRESUMEN
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.
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Antineoplásicos/química , Receptor EphB2/antagonistas & inhibidores , Receptor EphB2/química , Antineoplásicos/farmacología , Sitios de Unión , Línea Celular Tumoral , Cromatografía de Afinidad , Bases de Datos Factuales , Ensayo de Inmunoadsorción Enzimática , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Humanos , Espectrometría de Masas , Modelos Moleculares , Peso Molecular , Naftoquinonas/química , Naftoquinonas/farmacología , Fosforilación , Estructura Terciaria de Proteína , Relación Estructura-Actividad Cuantitativa , Receptor EphB2/metabolismo , Sulfuros/química , Sulfuros/farmacologíaRESUMEN
Utilizing frontal affinity chromatography with mass spectrometry detection (FAC-MS), we have identified novel applications in the discovery of small-molecule hits to protein targets that are difficult if not impossible to accomplish using traditional assays. We demonstrate for the first time an ability to distinguish between competitive ligands for the ATP and substrate sites of protein kinase C independently in the same experiment and show that ATP competitive ligands using a functionally inactive receptor tyrosine kinase can be identified. This ability of FAC-MS to simultaneously monitor binding at the ATP and substrate binding sites, as well as measure ligand binding to both active and inactive kinases, suggests that FAC-MS can be used as a "global kinase binding assay".
Asunto(s)
Cromatografía de Afinidad/métodos , Evaluación Preclínica de Medicamentos/métodos , Espectrometría de Masas/métodos , Inhibidores de Proteínas Quinasas/química , Proteínas Quinasas/química , Alcaloides/química , Alcaloides/metabolismo , Animales , Benzofenantridinas/química , Benzofenantridinas/metabolismo , Sitios de Unión , Unión Competitiva , Dominio Catalítico , Humanos , Imidazoles/química , Imidazoles/metabolismo , Ratones , Estructura Molecular , Péptidos/química , Péptidos/metabolismo , Fosforilación , Unión Proteica , Proteína Quinasa C-alfa/antagonistas & inhibidores , Proteína Quinasa C-alfa/química , Proteína Quinasa C-alfa/metabolismo , Inhibidores de Proteínas Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Quinasas/metabolismo , Piridinas/química , Piridinas/metabolismo , Quinazolinas/química , Quinazolinas/metabolismo , Receptor EphB2/antagonistas & inhibidores , Receptor EphB2/química , Receptor EphB2/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismoRESUMEN
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.