Cryo Electron Tomography of Native HIV-1 Budding Sites

The structure of immature and mature HIV-1 particles has been analyzed in detail by cryo electron microscopy, while no such studies have been reported for cellular HIV-1 budding sites. Here, we established a system for studying HIV-1 virus-like particle assembly and release by cryo electron tomography of intact human cells. The lattice of the structural Gag protein in budding sites was indistinguishable from that of the released immature virion, suggesting that its organization is determined at the assembly site without major subsequent rearrangements. Besides the immature lattice, a previously not described Gag lattice was detected in some budding sites and released particles; this lattice was found at high frequencies in a subset of infected T-cells. It displays the same hexagonal symmetry and spacing in the MA-CA layer as the immature lattice, but lacks density corresponding to NC-RNA-p6. Buds and released particles carrying this lattice consistently lacked the viral ribonucleoprotein complex, suggesting that they correspond to aberrant products due to premature proteolytic activation. We hypothesize that cellular and/or viral factors normally control the onset of proteolytic maturation during assembly and release, and that this control has been lost in a subset of infected T-cells leading to formation of aberrant particles

Intracellular lumen extension requires ERM-1-dependent apical membrane expansion and AQP-8-mediated flux

SUMMARY Many unicellular tubes such as capillaries form lumens intracellularly, a process that is not well understood. Here we show that the cortical membrane organizer ERM-1 is required to expand the intracellular apical/lumenal membrane and its actin undercoat during single-cell C.elegans excretory canal morphogenesis. We characterize AQP-8, identified in an ERM-1 overexpression (ERM-1[++]) suppressor screen, as a canalicular aquaporin that interacts with ERM-1 in lumen extension in a mercury-sensitive manner, implicating water-channel activity. AQP-8 is transiently recruited to the lumen by ERM-1, co-localizing in peri-lumenal cuffs interspaced along expanding canals. An ERM-1[++]-mediated increase in the number of lumen-associated canaliculi is reversed by AQP-8 depletion. We propose that the ERM-1-AQP-8 interaction propels lumen extension by translumenal flux, suggesting a direct morphogenetic effect of water-channel-regulated fluid pressure

The relationship between gastroesophageal reflux and asthma: an update

Asthma and gastroesophageal reflux disease (GERD) are both common conditions and, hence, they often coexist. However, asthmatics have been found to have a much greater prevalence of GERD symptoms than the general population. There remains debate regarding the underlying physiologic mechanism(s) of this relationship and whether treatment of GERD actually translates into improved asthma outcomes. Based on smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, current guidelines recommend a trial of GERD treatment for symptomatic asthmatics even without symptoms of GERD. However, recently a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton-pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. These data suggest empiric treatment of asymptomatic GERD in asthmatics is not a useful practice. This review article provides an overview of the epidemiology and pathophysiologic relationships between asthma and GERD as well as a summary of current data regarding links between treatment of GERD with asthma outcomes

Screening for Exercise-Induced Bronchoconstriction in College Athletes

Objective. Previous studies have reported that the prevalence of exercise-induced bronchoconstriction (EIB) in athletes is higher than that of the general population. There is increasing evidence that athletes fail to recognize and report symptoms of EIB. As a result, there has been debate whether athletes should be screened for EIB, particularly in high-risk sports. Methods. We prospectively studied 144 athletes from six different varsity sports at a large National Collegiate Athletic Association Division I collegiate athletic program. Baseline demographics and medical history were obtained and the presence of asthma symptoms during exercise was documented. Each athlete subsequently underwent a eucapnic voluntary hyperventilation (EVH) test to document the presence of EIB. Exhaled nitric oxide (eNO) quantification was performed immediately before EVH testing. EIB was defined as a ≥10% decline in forced expiratory volume in 1 second compared with baseline. Results. Only 4 of 144 (2.7%) athletes were EIB-positive after EVH testing. The presence of symptoms was not predictive of EIB as only 2 of the 64 symptomatic athletes (3%) were EIB-positive based on EVH testing. Two of the four athletes who were found to be EIB-positive denied such symptoms. The mean baseline eNO in the four EIB-positive athletes was 13.25 parts per billion (ppb) and 24.5 ppb in the EIB-negative athletes. Conclusions. Our data argue that screening for EIB is not recommended given the surprisingly low prevalence of EIB in the population we studied. In addition, the presence or absence of symptoms was not predictive of EIB and eNO testing was not effective in predicting EIB

Etiology of Dyspnea in Elite and Recreational Athletes

Background: Breathing complaints are common in athletes. Studies have suggested that the prevalence of asthma and exercise-induced bronchoconstriction (EIB) is higher in elite athletes than the general population. Vocal cord dysfunction (VCD) may mimic asthma and EIB as a cause of dyspnea in athletes. However, the majority of studies to date have primarily relied on symptoms to diagnose VCD, and there are limited data on coexistence of asthma, EIB, and/or VCD. It is well established that symptoms alone are inadequate to accurately diagnose EIB and VCD. Our goal was to define via objective testing the prevalence of asthma, EIB, VCD alone, or in combination in a cohort of athletes with respiratory complaints. Methods: A retrospective chart review was done of 148 consecutive athletes (collegiate, middle school, high school, and recreational) referred to a tertiary care center's asthma center for evaluation of respiratory complaints with exercise. An evaluation including medical history, physical examination, and objective testing including pulmonary function testing (PFT), eucapnic voluntary hyperventilation, and video laryngostroboscopy, were performed. Results: The most common symptom was dyspnea on exertion (96%), with < 1% complaining of either hoarseness or stridor. The most common diagnosis prior to referral was asthma (40%). Only 16% had PFTs prior to referral. Following evaluation by a pulmonologist, 52% were diagnosed with EIB, 17% with asthma, and 70% with VCD. Of those diagnosed with asthma before our evaluation, the diagnosis of asthma was confirmed, with PFTs in only 19 of 59 (32%) athletes based on our testing. Vocal cord dysfunction was more common in females and in adolescent athletes. Coexistence of multiple disorders was common, such as EIB and asthma (8%), EIB and VCD (31%), and VCD and asthma (6%). Conclusions: Asthma and EIB are common etiologies of dyspnea in athletes, both competitive and recreational. However, VCD is also common and can coexist with either asthma or EIB. Vocal cord dysfunction may contribute to exercise-related respiratory symptoms more frequently in middle school- and high school-aged athletes than in college athletes. Effective treatment of dyspnea requires appropriate identification and treatment of all disorders. Classic symptoms of stridor and/or hoarseness are often not present in athletes with VCD. Accurate diagnosis of asthma, EIB, and VCD requires objective testing and can prevent exposure of patients to medications that are ineffective and have potential adverse side effects. Furthermore, there is need for increased awareness of VCD as a common cause of respiratory complaints in athletes, either as a single diagnosis or in combination with EIB, especially in females, as well as middle school and high school athletes

Management of exercise-induced bronchospasm in NCAA athletic programs

PURPOSE: The prevalence of exercise-induced bronchospasm (EIB) is significantly higher in athletes than the general population, and can result in significant morbidity in young, competitive athletes. Guidelines emphasize that education and written treatment protocols improve clinical outcomes for asthmatics. Evidence also supports objective testing when exercise-induced bronchospasm is suspected, immediate availability of rescue inhalers, and involvement of asthma specialists in the care of asthmatic athletes. We sought to determine how EIB is managed at National Collegiate Athletic Association (NCAA) sports medicine programs. METHODS: A survey consisting of multiple-choice questions related to exercise-induced bronchospasm in athletes was sent electronically to 3200 athletic trainers affiliated with NCAA sports medicine programs. RESULTS: 541 athletic trainers responded. A minority of athletic trainers surveyed (21%) indicated an asthma management protocol exists at their institution. 22% indicated that pulmonologists are on staff in or consultants to the sports medicine department. Many indicated a short-acting beta-agonist is not required to be available at all practices (39%) and games (41%) and few athletic trainers indicated their programs utilize objective testing to diagnose EIB (17%). Regression modeling demonstrated education about EIB and involvement of pulmonologists significantly improved adherence to current consensus guidelines. CONCLUSIONS: Based on our data, many NCAA sports medicine programs do not manage athletes with EIB according to current consensus guidelines. This may result in inaccurate diagnoses and may be detrimental to clinical outcomes and the overall health of student athletes. Providing education about EIB and involvement of pulmonologists significantly increase adherence to guidelines which likely improves clinical care of athletes and potentially athletic performance

HIV and asthma, is there an association?

SummaryObjectiveTo evaluate whether asthma and airway hyper-responsiveness are associated with HIV infection.MethodsWe reviewed the literature on HIV-associated pulmonary diseases, pulmonary symptoms, and immune changes which may play a role in asthma. The information was analyzed comparing the pre-HAART era to the post-HAART era data.ResultsHIV-seropositive individuals commonly experience respiratory complaints yet it is unclear if the frequency of these complaints have changed with the initiation of HAART. Changes in pulmonary function testing and serum IgE are seen with HIV infection even in the post-HAART era. An increased prevalence of asthma among HIV-seropositive children treated with HAART has been reported.ConclusionThe spectrum of HIV-associated pulmonary disease has changed with the introduction of HAART. Current data is limited to determine if asthma and airway hyper-responsiveness are more common among HIV-seropositive individuals treated with HAART

The Prevalence of Asthma in an NCAA Division I Collegiate Athletic Program

Purpose. To determine the prevalence of asthma among all varsity athletes in a large National Collegiate Athletic Association (NCAA) Division I program. Methods. We retrospectively reviewed the medical records for all varsity athletes at The Ohio State University (OSU). Data were abstracted from patient charts that contained a Medical Health Questionnaire, annual physical examinations, and medical encounters by the OSU Sports Medicine staff. A diagnosis of asthma was defined by self-report of physician diagnosis as recorded in the medical record. Results. Overall, 130 of 763 (17.0%) athletes had a diagnosis of asthma. Females (67/280 or 23.9%) had a significantly higher prevalence of asthma than males (63/483 or 13.0%) (p value = 0.001). There was no significant difference in the prevalence of asthma between high- and low-ventilation sports. (p value = 0.201). Conclusions. The prevalence of asthma among varsity athletes at The Ohio State University is 17.0%, which is significantly higher than the reported prevalence of asthma in the general United States population between 18 to 24 years of age. More females had asthma in our study population than males. These data will allow for future studies and development of focused screening programs of collegiate athletes