Purpose and aim of the study Bronchial epithelial cells play an important role in immune response against viral infections. Toll-like receptor 3 (TLR3) is a pathogen recognition receptor that recognizes viral double-stranded RNA (dsRNA). Activation of TLR3 induces the expression of interferon (IFN)-β, and newly synthesized IFN-β exhibits anti-viral activity by upregulating the expression of IFN-stimulated genes (ISGs). ISG56 encodes a multifunctional protein with tetratricopeptide motifs and is involved in anti-viral reactions through various mechanisms. Expression of chemokines such as CXCL10, which induces leukocyte chemotaxis, is essential for defense against airway microbes. However, regulation of chemokine expression by ISG56 in bronchial epithelial cells has not been fully investigated. The aim of this study was to examine the expression of ISG56 and its role in CXCL10 production in BEAS-2B bronchial epithelial cells treated with dsRNA.Materials and methods BEAS-2B bronchial epithelial cells were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic TLR3 ligand. The mRNA and protein expression levels of ISG 56 were analyzed by quantitative reverse transcription polymerase chain reaction and western blotting. The effect of knocking down TLR3, IFN-β, and ISG56 was examined using RNA interference. The protein expression of CXCL10 in culture medium was measured using an enzyme-linked immunosorbent assay.Results Poly IC induced ISG56 expression in a concentration- and time- dependent manner. RNA interference showed that ISG56 induction was inhibited by knockdown of TLR3 or IFN-β and that ISG 56 knockdown decreased CXCL10 expression.Conclusions ISG56 was induced by poly IC through TLR3/IFN-β axis, and ISG56 may positively regulated CXCL10 expression in BEAS-2B cells. ISG56 may modulate anti-viral innate immunity, at least in part, by regulating the expression of CXCL10 in bronchial epithelial cells.Issue Despite clear relevance, need, descriptive literature, and student interest, few schools offer required curriculum to develop leadership skills. This paper outlines a proposed shared vision for leadership development drawn from a coalition of diverse medical schools. We advocate that leadership development is about self (looking inward), teams (not hierarchy), and change (looking outward). We propose that leadership development is for all medical students, not for a subset, and we believe that leadership curricula and programs must be experiential and applied. Evidence This paper also draws on the current literature and the experience of medical schools participating in the American Medical Association's (AMA) Accelerating Change in Medical Education Consortium, confronts the common arguments against leadership training in medical education, and provides three cross-cutting principles that we believe must each be incorporated in all medical student-centered leadership development programs as they emerge and evolve at medical schools. Implications By confronting common arguments against leadership training and providing a framework for such training, we give medical educators important tools and insights into developing leadership training for all students at their institutions.Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant (HTx) recipient mortality. Little is known about the prototypes of CAV trajectories at the population level. We aimed to identify the different evolutionary profiles of CAV and to determine the respective contribution of immune and non-immune factors in CAV development. Methods HTx recipients from four academic centers (Pitié-Salpêtrière & Georges Pompidou Hospital, Paris, Katholieke Universiteit Leuven, Cedars-Sinai, Los Angeles; 2004 to 2016). Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessments of clinical, histological and immunological parameters. The main outcome was a prediction for CAV trajectory. We identified CAV trajectories using unsupervised latent class mixed models. We then identified the independent predictive variables of the CAV trajectories and their association with mortality. Results A total of 1301 patients werees manifested consistently in the US independent cohort with similar discrimination (0.97) and in different clinical scenarios and showed gradients for overall cause mortality (p less then 0.001). ConclusionsIn a large multicenter and highly phenotyped prospective cohort of HTx recipients, we identified four CAV trajectories and their respective independent predictive variables. Our results provide the basis for a trajectory-based assessment of HTx patients for early risk stratification, patient monitoring and clinical trials. Clinical Trial Registration URL https//clinicaltrials.gov Unique Identifier NCT04117152.Introduction Peripheral neuropathic pain is highly disabling conditions for patients and a challenge for neurologists and pain physicians. Although many drugs have been assessed in scientific studies, few have demonstrated a clear clinical efficacy against neuropathic pain. Moreover, the paucity of data regarding their safety raised the question on the benefit-risk ratio when used in patients experiencing peripheral neuropathies.Areas covered The authors conducted a review of double-blind, placebo-controlled, randomized clinical trials to assess the safety of medications used to treat neuropathic pain. This first review was focused on antidepressant and antiepileptic medications. The aim was to provide an overview of the treatment-emergent adverse events (≥10%) and the serious adverse effects described in clinical trials.Expert opinion Among antiepileptics and antidepressants, duloxetine appeared to have the most detailed safety for the treatment of peripheral neuropathic pain. Over all studies, the most commonly reported adverse effects were dizziness, drowsiness, nausea, and constipation. Only 20.0% of the included studies (N=90) presented a good description of adverse effects that included a statistical comparison versus a placebo group. selleck products Important methodological improvements must be made to improve the assessment of medication safety in future clinical trials.