Highlights d M. restricta is associated with the colonic mucosa in Crohn's disease (CD) patients d M. restricta exacerbates colitis in wild-type and gnotobiotic mice d M. restricta is found in CD patients with a disease-linked polymorphism in CARD9 d Malassezia-exacerbated colitis in mice requires signaling via CARD9

Fungi are increasingly being recognized as common members of the microbiomes found on nearly all mucosal surfaces, and interest is growing in understanding how these organisms may contribute to health and disease. In this review, we investigate recent developments in our understanding of the fungal microbiota or “mycobiota” including challenges faced in characterizing it, where these organisms are found, their diversity, and how they interact with host immunity. Growing evidence indicates that like the bacterial microbiota, the fungal microbiota is often altered in disease states, and increasingly studies are being designed to probe the functional consequences of such fungal dysbiosis on health and disease.

The gastrointestinal microbiota influences immune function throughout the body. The gut-lung axis refers to the concept that alterations of gut commensal microorganisms can have a distant effect on immune function in the lung. Overgrowth of intestinal Candida albicans has been previously observed to exacerbate allergic airways disease in mice, but whether subtler changes in intestinal fungal microbiota can affect allergic airways disease is less clear. In this study we have investigated the effects of the population expansion of commensal fungus Wallemia mellicola without overgrowth of the total fungal community. Wallemia spp. are commonly found as a minor component of the commensal gastrointestinal mycobiota in both humans and mice. Mice with an unaltered gut microbiota community resist population expansion when gavaged with W. mellicola; however, transient antibiotic depletion of gut microbiota creates a window of opportunity for expansion of W. mellicola following delivery of live spores to the gastrointestinal tract. This phenomenon is not universal as other commensal fungi (Aspergillus amstelodami, Epicoccum nigrum) do not expand when delivered to mice with antibiotic-depleted microbiota. Mice with Wallemia-expanded gut mycobiota experienced altered pulmonary immune responses to inhaled aeroallergens. Specifically, after induction of allergic airways disease with intratracheal house dust mite (HDM) antigen, mice demonstrated enhanced eosinophilic airway infiltration, airway hyperresponsiveness (AHR) to methacholine challenge, goblet cell hyperplasia, elevated bronchoalveolar lavage IL-5, and enhanced serum HDM IgG1. This phenomenon occurred with no detectable Wallemia in the lung. Targeted amplicon sequencing analysis of the gastrointestinal mycobiota revealed that expansion of W. mellicola in the gut was associated with additional alterations of bacterial and fungal commensal communities. We therefore colonized fungus-free Altered Schaedler Flora (ASF) mice with W. mellicola. ASF mice colonized with W. mellicola experienced enhanced severity of allergic airways disease compared to fungus-free control ASF mice without changes in bacterial community composition.

Background-Cardiopulmonary exercise testing (CPX) with measurement of peak oxygen uptake (VO 2 ) is a powerful test for assessment and quantification of functional impairment resulting from cardiovascular disease. The safety of CPX has been established in patients with coronary artery disease and congestive heart failure, but clinical use of CPX in other cardiac diseases has been limited, in part because of a paucity of safety data. This study investigates the safety of CPX in a heterogeneous cohort of patients with a wide variety of underlying high-risk cardiac diagnoses. Methods and Results-This single-center retrospective review examined 5060 CPX studies performed in 4250 unique patients, including 1748 (35%) female subjects and 686 (14%) subjects aged Ն75 years. The primary end point was major adverse event during stress testing. The study population included patients with a variety of high-risk cardiac diseases, including congestive heart failure (nϭ1289, 25.5%), hypertrophic cardiomyopathy (nϭ598, 11.8%), pulmonary hypertension (nϭ194, 3.8%), and aortic stenosis (nϭ212, 4.2%). This patient population generally had severe functional impairment, including 1192 (24%) patients with peak VO 2 Ͻ14 mL/kg/min. Eight adverse events occurred during CPX, for an adverse event rate of 0.16%. The most common adverse event (nϭ6) was sustained ventricular tachycardia. There were no fatal events. Conclusions-CPX is generally a safe procedure, even in a population with underlying high-risk cardiovascular diagnoses. (Circulation. 2012;126:2465-2472.)

No abstract

Pneumocystis is a genus of ascomycetous fungi that are highly morbid pathogens in immunosuppressed humans and other mammals. Pneumocystis cannot easily be propagated in culture, which has greatly hindered understanding of its pathobiology. The Pneumocystis life cycle is intimately associated with its mammalian host lung environment, and life cycle progression is dependent on complex interactions with host alveolar epithelial cells and the extracellular matrix. The Pneumocystis cell wall is a varied and dynamic structure containing a dominant major surface glycoprotein, β-glucans and chitins that are important for evasion of host defenses and stimulation of the host immune system. Understanding of Pneumocystis cell signaling pathways is incomplete, but much has been deduced by comparison of the Pneumocystis genome with homologous genes and proteins in related fungi. In this mini-review, the pathobiology of Pneumocystis is reviewed, with particular focus on the life cycle, cell wall components and cell signal transduction.

The burden of pleural diseases continues to rise and affects an increasingly complex and aging patient population. As such, thoracentesis is one of the most common procedures performed by respiratory physicians, as pleural fluid analysis can establish the diagnosis of pleural effusions in approximately 75% of the cases. When a diagnosis is not reached, options include image-guided biopsies, only possible when focal pleural lesions can be identified by computed tomography or ultrasound; closed pleural biopsies, associated with a relatively low diagnostic yield; and surgical pleural biopsies, which typically require general anesthesia and a hospital stay. Medical thoracoscopy addresses some of the limitations of these techniques, allows a comprehensive pleural examination and targeted pleural biopsies, and offers the possibility of treatment of recurrence in the same setting. As such, medical thoracoscopy is ideally positioned as a valuable tool in the diagnosis of unexplained exudative pleural effusions.

Background Point-of-care (POC) ultrasound has been shown to improve procedural outcomes and physical examination accuracy in multiple settings. There are limited data regarding the optimal way to train nonradiologists in POC ultrasound. This is a primary barrier to more widespread use of ultrasound in the physical examination. Objective We created a workshop to instruct postgraduate year (PGY)-2 and PGY-3 internal medicine residents in POC ultrasound imaging of the abdominal aorta and kidneys. Methods A half-day simulation center workshop was created to review ultrasound operations and teach residents to independently obtain ultrasound images of the abdominal aorta and kidneys on standardized patients with normal anatomy. The workshop incorporated didactic instruction and hands-on ultrasound practice in small groups. Each resident's ability to independently obtain ultrasound images was assessed using a preworkshop and postworkshop skills examination with a standardized patient. Resident knowledge and attitudes toward POC ultrasound were also assessed using a preworkshop and postworkshop test and survey. Results A total of 58 residents completed the workshop, and 84% were able to independently obtain high-quality images of the abdominal aorta and kidney after workshop completion, compared with 16% on the preworkshop test. Residents demonstrated a statistically significant increase in their self-reported confidence with ultrasound operation and image acquisition. Conclusions Training using standardized patients can prepare residents to independently obtain POC ultrasound images of the aorta and kidneys. Training resulted in increased resident confidence with POC ultrasound and self-reported likelihood of future use.