Johns Hopkins University School of Medicine

About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America

Abstract: It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status.

Abstract: Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.

Toward Evidence-Based Medical Statistics. 1: The P Value Fallacy

Abstract: An important problem exists in the interpretation of modern medical research data: Biological understanding and previous research play little formal role in the interpretation of quantitative results. This phenomenon is manifest in the discussion sections of research articles and ultimately can affect the reliability of conclusions. The standard statistical approach has created this situation by promoting the illusion that conclusions can be produced with certain "error rates," without consideration of information from outside the experiment. This statistical approach, the key components of which are P values and hypothesis tests, is widely perceived as a mathematically coherent approach to inference. There is little appreciation in the medical community that the methodology is an amalgam of incompatible elements, whose utility for scientific inference has been the subject of intense debate among statisticians for almost 70 years. This article introduces some of the key elements of that debate and traces the appeal and adverse impact of this methodology to the P value fallacy, the mistaken idea that a single number can capture both the long-run outcomes of an experiment and the evidential meaning of a single result. This argument is made as a prelude to the suggestion that another measure of evidence should be used--the Bayes factor, which properly separates issues of long-run behavior from evidential strength and allows the integration of background knowledge with statistical findings.

Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury.

Abstract: Accumulating evidence suggests that oxidative stress plays a central role in the pathogenesis of many pulmonary diseases including adult respiratory distress syndrome, emphysema, asthma, bronchopulmonary dysplasia, and interstitial pulmonary fibrosis. The morbidity and mortality of these diseases remain high even with optimal medical management. In our attempts to devise new therapies for these disorders, it is crucial to improve our understanding of the basic mechanism(s) of oxidant-induced lung injury. A major line of investigation seeks to characterize the cellular and molecular responses of the lung to oxidant insults. Much progress has been made in our understanding of the role of the "classic" antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) in mediating the lung's resistance against oxidant lung injury. However, it is becoming clear that other oxidant-induced gene products may also play vital roles in the lung's adaptive and/or protective response to oxidative stress. One such stress-response protein is heme oxygenase-1, HO-1. Since the identification of HO-1 in 1968, many of the studies involving this enzyme were understandably focused on the regulation and function of HO-1 in heme metabolism. This emphasis is self-evident as HO-1 catalyzes the first and rate-limiting step in heme degradation. Interestingly, however, evidence accumulated over the past 25 years demonstrates that HO-1 is induced not only by the substrate heme but also by a variety of non-heme inducers such as heavy metals, endotoxin, heat shock, inflammatory cytokines, and prostaglandins. The chemical diversity of HO-1 inducers led to the speculation that HO-1, besides its role in heme degradation, may also play a vital function in maintaining cellular homeostasis. Further support for this hypothesis was provided by Tyrrell and colleagues who showed in 1989 that HO-1 is also highly induced by a variety of agents causing oxidative stress. Subsequently, many investigators have focused their attention on the function and regulation of HO-1 in various in vitro and in vivo models of oxidant-mediated cellular and tissue injury. The magnitude of HO-1 induction after oxidative stress and the wide distribution of this enzyme in systemic tissues coupled with the intriguing biological activities of the catalytic byproducts, carbon monoxide, iron, and bilirubin, makes HO-1 a highly attractive and interesting candidate stress-response protein which may play key role(s) in mediating protection against oxidant-mediated lung injury. This review will focus on the current understanding of the physiological significance of HO-1 induction and the molecular regulation of HO-1 gene expression in response to oxidative stress. We hope that this discussion will stimulate interest and investigations into a field which is still largely uncharted in the pulmonary research community.