A nationwide assessment of perceptions of research-intense academic careers among predoctoral MD and MD-PhD trainees.

Introduction: While previous studies have described career outcomes of physician-scientist trainees after graduation, trainee perceptions of research-intensive career pathways remain unclear. This study sought to identify the perceived interests, factors, and challenges associated with academic and research careers among predoctoral MD trainees, MD trainees with research-intense (>50%) career intentions (MD-RI), and MD-PhD trainees.

Methods: A 70-question survey was administered to 16,418 trainees at 32 academic medical centers from September 2012 to December 2014.

Factors associated with underrepresented minority physician scientist trainee career choices.

Background: Recently, there have been concerted efforts to improve racial and ethnic diversity in the physician-scientist workforce. Identifying factors associated with career choices among those underrepresented in medicine and science is a necessary first step to advance this objective. The aim of the present study was to assess the attitudes and factors associated with academic and research career interests among underrepresented predoctoral physician-scientists.

Training the physician-scientist: views from program directors and aspiring young investigators.

There is growing concern that the physician-scientist is endangered due to a leaky training pipeline and prolonged time to scientific independence (1). The NIH Physician-Scientist Workforce Working Group has concluded that as many as 1,000 individuals will need to enter the pipeline each year to sustain the workforce (2). Moreover, surveys of postgraduate training programs document considerable variability in disposition and infrastructure (3).

Early-life antibiotics attenuate regulatory T cell generation and increase the severity of murine house dust mite-induced asthma.

Introduction: Early-life exposure to antibiotics (ABX) has been linked to increases in asthma severity and prevalence in both children and laboratory animals. We explored the immunologic mechanisms behind this association using a mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure.

Methods: Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced.

Regulation of IgE activity in inhalational tolerance via formation of IgG anti-IgE/IgE immune complexes.

Background: Allergic asthma is an inflammatory disorder of the airways that results from inappropriate production of IgE against harmless, environmental antigens. Sequestration of free IgE using humanized IgG anti-IgE is an effective therapy for asthma and other atopic disorders. However, the status of free IgE in subjects who have naturally developed immune tolerance to inhaled antigens has not been well studied.

Sexual and gender minority health in medical curricula in new England: a pilot study of medical student comfort, competence and perception of curricula.

Background: Sexual and gender minority (SGM) individuals experience high rates of harassment and discrimination when seeking healthcare, which contributes to substantial healthcare disparities. Improving physician training about gender identity, sexual orientation, and the healthcare needs of SGM patients has been identified as a critical strategy for mitigating these disparities. In 2014, the Association of American Medical Colleges (AAMC) published medical education competencies to guide undergraduate medical education on SGM topics.

Exploring intentions of physician-scientist trainees: factors influencing MD and MD/PhD interest in research careers.

Background: Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates.

Breathing Better Through Bugs: Asthma and the Microbiome.

Asthma is a highly heterogeneous disease characterized by inflammation of the airways, which invokes symptoms such as wheeze, dyspnea, and chest tightness. Asthma is the product of multiple interconnected immunological processes and represents a constellation of related, but distinct, disease phenotypes. The prevalence of asthma has more than doubled since the 1980s, and efforts to understand this increase have inspired consideration of the microbiome as a key player in the pathophysiology and regulation of this disease.

Microbiome Changes during Tuberculosis and Antituberculous Therapy.

The critical role of commensal microbiota in the human body has been increasingly recognized, and our understanding of its implications in human health and disease has expanded rapidly. The lower respiratory tract contains diverse communities of microbes known as lung microbiota, which are present in healthy individuals and in individuals with respiratory diseases. The dysbiosis of the airway microbiota in pulmonary tuberculosis (TB) may play a role in the pathophysiological processes associated with TB disease.

Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation.

Abolishing the inhibitory signal of intracellular cAMP is a prerequisite for effector T (Teff) cell function. The regulation of cAMP within leukocytes critically depends on its degradation by cyclic nucleotide phosphodiesterases (PDEs). We have previously shown that PDE8A, a PDE isoform with 40-100-fold greater affinity for cAMP than PDE4, is selectively expressed in Teff vs.

Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers.

Background: One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model.

The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection.

Advances in next generation sequencing (NGS) technology have provided the tools to comprehensively and accurately characterize the microbial community in the respiratory tract in health and disease. The presence of commensal and pathogenic bacteria has been found to have important effects on the lung immune system. Until relatively recently, the lung has received less attention compared to other body sites in terms of microbiome characterization, and its study carries special technological difficulties related to obtaining reliable samples as compared to other body niches.

Label-free and depth resolved optical sectioning of iron-complex deposits in sickle cell disease splenic tissue by multiphoton microscopy.

Multiphoton microscopy (MPM) imaging of intrinsic two-photon excited fluorescence (TPEF) is performed on humanized sickle cell disease (SCD) mouse model splenic tissue. Distinct morphological and spectral features associated with SCD are identified and discussed in terms of diagnostic relevance. Specifically, spectrally unique splenic iron-complex deposits are identified by MPM; this finding is supported by TPEF spectroscopy and object size to standard histopathological methods.

Long-Term Exposure to House Dust Mite Leads to the Suppression of Allergic Airway Disease Despite Persistent Lung Inflammation.

Background: Allergic asthma is a major cause of worldwide morbidity and results from inadequate immune regulation in response to innocuous, environmental antigens. The need exists to understand the mechanisms that promote nonreactivity to human-relevant allergens such as house dust mite (HDM) in order to develop curative therapies for asthma. The aim of our study was to compare the effects of short-, intermediate- and long-term HDM administration in a murine asthma model and determine the ability of long-term HDM exposure to suppress allergic inflammation.

The sickle cell mouse lung: proinflammatory and primed for allergic inflammation.

Comorbid asthma in sickle cell disease (SCD) confers higher rates of vaso-occlusive pain and mortality, yet the physiological link between these two distinct diseases remains puzzling. We used a mouse model of SCD to study pulmonary immunology and physiology before and after the induction of allergic airway disease (AAD). SCD mice were sensitized with ovalbumin (OVA) and aluminum hydroxide by the intraperitoneal route followed by daily, nose-only OVA-aerosol challenge to induce AAD.

Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells.

The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD).

Looking in the mouth for noninvasive gene expression-based methods to detect oral, oropharyngeal, and systemic cancer.

Noninvasive diagnosis, whether by sampling body fluids, body scans, or other technique, has the potential to simplify early cancer detection. A classic example is Pap smear screening, which has helped to reduce cervical cancer 75% over the last 50 years. No test is error-free; the real concern is sufficient accuracy combined with ease of use.

Brand specific responses to smokeless tobacco in a rat lip canal model.

Background: Different compositions of smokeless tobacco (ST) are widely thought to cause oral carcinoma at different rates but there is little direct evidence for this hypothesis.

Methods: We used a rat lip canal model to examine the mucosal changes induced by chronic daily exposure to four different brands of ST: Skoal, Copenhagen, Ettan Swedish Snus, and Stonewall, differing in measured levels of: tobacco specific nitrosamines (TSNAs), unprotonated nicotine, moisture, and pH.

Results: Exposure to the lip canal for 12 months produced changes in the mucosa marked by increases in S phase and M phase cells for the Skoal and Copenhagen exposed rats.