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.

HPV-associated head and neck cancer: a virus-related cancer epidemic

Abstract: Summary A rise in incidence of oropharyngeal squamous cell cancer—specifically of the lingual and palatine tonsils—in white men younger than age 50 years who have no history of alcohol or tobacco use has been recorded over the past decade. This malignant disease is associated with human papillomavirus (HPV) 16 infection. The biology of HPV-positive oropharyngeal cancer is distinct with P53 degradation, retinoblastoma RB pathway inactivation, and P16 upregulation. By contrast, tobacco-related oropharyngeal cancer is characterised by TP53 mutation and downregulation of CDKN2A (encoding P16). The best method to detect virus in tumour is controversial, and both in-situ hybridisation and PCR are commonly used; P16 immunohistochemistry could serve as a potential surrogate marker. HPV-positive oropharyngeal cancer seems to be more responsive to chemotherapy and radiation than HPV-negative disease. HPV 16 is a prognostic marker for enhanced overall and disease-free survival, but its use as a predictive marker has not yet been proven. Many questions about the natural history of oral HPV infection remain under investigation. For example, why does the increase in HPV-related oropharyngeal cancer dominate in men? What is the potential of HPV vaccines for primary prevention? Could an accurate method to detect HPV in tumour be developed? Which treatment strategies reduce toxic effects without compromising survival? Our aim with this review is to highlight current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma, and to describe unresolved issues.

Relationship of Physical Activity and Television Watching With Body Weight and Level of Fatness Among Children Results From the Third National Health and Nutrition Examination Survey

Abstract: Context.—Physical inactivity contributes to weight gain in adults, but whether this relationship is true for children of different ethnic groups is not well established.Objective.—To assess participation in vigorous activity and television watching habits and their relationship to body weight and fatness in US children.Design.—Nationally representative cross-sectional survey with an in-person interview and medical examination.Setting and Participants.—Between 1988 and 1994, 4063 children aged 8 through 16 years were examined as part of the National Health and Nutrition Examination Survey III. Mexican Americans and non-Hispanic blacks were oversampled to produce reliable estimates for these groups.Main Outcome Measures.—Episodes of weekly vigorous activity and daily hours of television watched, and their relationship to body mass index and body fatness.Results.—Eighty percent of US children reported performing 3 or more bouts of vigorous activity each week. This rate was lower in non-Hispanic black and Mexican American girls (69% and 73%, respectively). Twenty percent of US children participated in 2 or fewer bouts of vigorous activity per week, and the rate was higher in girls (26%) than in boys (17%). Overall, 26% of US children watched 4 or more hours of television per day and 67% watched at least 2 hours per day. Non-Hispanic black children had the highest rates of watching 4 or more hours of television per day (42%). Boys and girls who watch 4 or more hours of television each day had greater body fat (P<.001) and had a greater body mass index (P<.001) than those who watched less than 2 hours per day.Conclusions.—Many US children watch a great deal of television and are inadequately vigorously active. Vigorous activity levels are lowest among girls, non-Hispanic blacks, and Mexican Americans. Intervention strategies to promote lifelong physical activity among US children are needed to stem the adverse health consequences of inactivity.

Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened.

Abstract: The steroidal alkaloid cyclopamine has both teratogenic and antitumor activities arising from its ability to specifically block cellular responses to vertebrate Hedgehog signaling. We show here, using photoaffinity and fluorescent derivatives, that this inhibitory effect is mediated by direct binding of cyclopamine to the heptahelical bundle of Smoothened (Smo). Cyclopamine also can reverse the retention of partially misfolded Smo in the endoplasmic reticulum, presumably through binding-mediated effects on protein conformation. These observations reveal the mechanism of cyclopamine's teratogenic and antitumor activities and further suggest a role for small molecules in the physiological regulation of Smo.

The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises.

Abstract: The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.

The Hedgehog and Wnt signalling pathways in cancer

Abstract: The Wnt and Hedgehog (Hh) signalling pathways have long been known to direct growth and patterning during embryonic development. Recent evidence also implicates these pathways in the postembryonic regulation of stem-cell number in epithelia such as those of the skin and intestine, which undergo constant renewal. A pathological role for the Wnt and Hh pathways has emerged from studies showing a high frequency of specific human cancers associated with mutations that constitutively activate the transcriptional response of these pathways. This article focuses on Hh and Wnt signal transduction and reviews evidence suggesting that tumorigenesis associated with pathway activation may result from mis-specification of cells towards stem-cell or stem cell-like fates.