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Transactions of the American Clinical and Climatological Association

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https://www.readbyqxmd.com/read/28790519/errata
#1
(no author information available yet)
[This corrects the article on p. lxxxi in vol. 127, PMID: 28066079.].
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790518/coordinated-management-of-academic-health-centers
#2
Jeffrey R Balser, William W Stead
Academic health centers (AHCs) are the nation's primary resource for healthcare discovery, innovation, and training. US healthcare revenue growth has declined sharply since 2009, and is forecast to remain well below historic levels for the foreseeable future. As the cost of education and research at nearly all AHCs is heavily subsidized through large transfers from clinical care margins, our institutions face a mounting crisis. Choices centering on how to increase the cost-effectiveness of the AHC enterprise require unprecedented levels of alignment to preserve an environment that nurtures creativity...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790516/the-molecular-basis-of-portal-hypertension
#3
REVIEW
Don C Rockey
Cirrhosis leads to portal hypertension and vascular abnormalities in multiple vascular beds. There is intense vasoconstriction in the liver and the kidneys, but also vasodilation in the other vascular beds, including the periphery, lungs, brain, and mesentery. The derangement in each of these beds leads to specific clinical disease. The vasoconstrictive phenotype in the liver ultimately leads to clinical portal hypertension, and is caused by an imbalance of vasoconstrictive and vasorelaxing molecules, which will be the focus of this review...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790515/transient-receptor-potential-melastatin-channel-family-member-2-friend-or-foe
#4
REVIEW
Joseph Y Cheung, Barbara A Miller
Transient receptor potential melastatin 2 (Trpm2) channels are nonvoltage-activated channels permeable to monovalent and divalent cations, and are expressed in heart, brain, kidney, vasculature, and hematopoietic cells. Trpm2 is overexpressed in bladder, lung, breast, liver, head, and neck cancers. Classically, Trpm2 activation induces cell injury and death by Ca2+ overload or enhanced inflammatory response. Recent studies show that Trpm2 protects lungs from endotoxin-induced injury by reducing reactive oxygen species production in phagocytes; and improves cardiac function after ischemia-reperfusion injury by preserving mitochondrial respiration and cellular adenosine triphosphate levels while decreasing reactive oxygen species levels...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790514/the-vhl-tumor-suppressor-gene-insights-into-oxygen-sensing-and-cancer
#5
REVIEW
William G Kaelin
Mammalian cells sense changes in oxygen and transduce that information into adaptive changes in gene expression using a conserved pathway that converges on the heterodimeric transcription factor called hypoxia-inducible factor (HIF), which contains a labile alpha subunit and a stable beta subunit. In the presence of oxygen, the alpha subunit is hydroxylated on one (or both) of two highly conserved prolyl residues by an Egg-Laying Defective Nine (EglN) [also called Prolyl Hydroxylase Domain (PHD)] dioxygenase, which recruits an ubiquitin ligase complex containing the VHL tumor suppressor gene product...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790513/the-jeremiah-metzger-lecture-cancer-in-the-twenty-first-century-an-inside-view-from-an-outsider
#6
Edward J Benz
Cancer is not a single disease. The term refers to literally hundreds of illnesses sharing common features: inappropriate proliferation of imperfectly differentiated cell types, invasion of nearby vital structures, and spread to distant sites (metastasis). Invasiveness and metastasis distinguish cancers from benign tumors such as fibroids and meningiomas. Yet, each type is distinct, possessed of defining morphologic, histologic, biochemical, and genomic features that have allowed oncologists to develop a nosology that guides diagnosis and therapy...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790510/fear-and-loathing-on-the-campaign-trail-what-the-election-means-for-u-s-health-care-and-the-health-of-american-democracy
#7
REVIEW
Robert B Doherty
This paper analyzes four trends that are affecting the 2016 election: changing US demographics and the reaction to them, a growing distrust of government, increased polarization and government gridlock, and the rise of populism. It compares the views of candidates Hillary Rodham Clinton and Donald S. Trump on the Affordable Care Act, climate change, prescription drug pricing, prevention of injuries and deaths from firearms, and the opioids epidemic; and offers perspectives on the potential impact of the election not only on U...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790505/the-privilege-of-being-a-physician-and-the-immutable-values-of-the-medical-profession
#8
REVIEW
Gustavo R Heudebert
The medical profession has been, is, and will continue to be under siege by a variety of sources most of which are external to the profession and not under our control. The consequences of this unrelenting pressure are leading to burnout, early retirement, and low career satisfaction. Arguably, these and perhaps other not-well-recognized factors has influenced the well-being of physicians and culminated in a high suicide rate in the profession. However, the pressures that our profession have been under over the last 2,500 years, albeit less pronounced than the current ones, have been successfully navigated by going back to the foundational values of medicine that are both intemporal and immutable...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790504/cigarette-smoke-and-dna-cleavage-promote-lung-inflammation-and-emphysema
#9
REVIEW
Farrah Kheradmand, R You, Bon Hee Gu, D B Corry
Smoking-related lung diseases are among the most preventable and incurable ailments in the world. Smokers are at increased risk of developing chronic obstructive pulmonary disease that can be further complicated by emphysema and lung cancer. A subset of former smokers shows persistent lung inflammation and progressive loss of lung function, indicating a role for activation of acquired immunity in smoking-induced lung diseases. In addition to the well-established noxious effects of volatile compounds in cigarette smoke, incomplete combustion of tobacco generates nano-sized carbon black (nCB) that accumulate in lung myeloid dendritic cells and macrophages...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790503/mast-cells-and-ige-can-enhance-survival-during-innate-and-acquired-host-responses-to-venoms
#10
REVIEW
Stephen J Galli, Philipp Starkl, Thomas Marichal, Mindy Tsai
Mast cells and immunoglobulin E (IgE) antibodies are thought to promote health by contributing to host responses to certain parasites, but other beneficial functions have remained obscure. Venoms provoke innate inflammatory responses and pathology reflecting the activities of the contained toxins. Venoms also can induce allergic sensitization and development of venom-specific IgE antibodies, which can predispose some subjects to exhibit anaphylaxis upon subsequent exposure to the relevant venom. We found that innate functions of mast cells, including degradation of venom toxins by mast cell-derived proteases, enhanced survival in mice injected with venoms from the honeybee, two species of scorpion, three species of poisonous snakes, or the Gila monster...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790502/actin-up-in-the-nucleus-regulation-of-actin-structures-modulates-mesenchymal-stem-cell-differentiation
#11
Janet Rubin, Buer Sen
Stem cells respond to environmental signals that induce their differentiation to cells that make up specialized tissues and organs. Our laboratory has focused on bone marrow mesenchymal stem cells (MSCs) that supply bone osteoblasts and marrow adipocytes, an output that appears to be reciprocal. Case in point: exercise promotes osteogenesis and bone formation, and inhibits marrow adipose accrual. A mechanically induced signal pathway concentrating on preserving β-catenin also causes increased structure of the actin cytoskeleton, both of which inhibit adipogenesis...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790501/conquering-the-challenges-of-genotypic-and-phenotypic-tumor-heterogeneity-to-realize-the-promise-of-personalized-cancer-therapy-the-role-of-academia
#12
Sofia Merajver, Sameer Phadke, Matthew Soellner
The advent of rapid and progressively more affordable sequencing and gene expression studies have spurred research on therapies for cancer targeted to specific gene alterations. With few exceptions, such as those cancers with either a paucity of mutations or major chromosomal rearrangements driving the neoplastic transformation, the approaches based on one mutational target-one drug have achieved only modest outcomes in cancer. Using the paradigm of aggressive breast cancers, we will show the mathematical explanation that predicts our failures and indicates a plausible way forward...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790500/personomics-and-precision-medicine
#13
Roy C Ziegelstein
The importance of knowing patients as individuals has been highlighted throughout the history of medicine. However, shorter visits, electronic documentation, reliance on technology, and increasing linguistic and cultural differences between patients and physicians create more challenges to effective communication than ever before. Perhaps more concerning is the greater emphasis on aspects of care considered more precisely measurable and quantifiable, the sum of which is sometimes felt to represent the patient better than knowledge of the patient himself...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790497/do-stories-deserve-a-place-in-medical-journals
#14
Christine Laine
Given the high costs of producing a medical journal, the need to publish clinically relevant information, and the fact that many journals can publish only a small fraction of the many scientific papers they consider, it seems reasonable to wonder whether stories deserve a place in a scholarly medical journal. Using examples from Annals of Internal Medicine, this commentary discusses the important role stories can serve in scholarly medical journals.
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790493/substance-misuse-and-substance-use-disorders-why-do-they-matter-in-healthcare
#15
A Thomas McLellan
This paper first introduces important conceptual and practical distinctions among three key terms: substance "use," "misuse," and "disorders" (including addiction), and goes on to describe and quantify the important health and social problems associated with these terms. National survey data are presented to summarize the prevalence and varied costs associated with misuse of alcohol, illegal drugs, and prescribed medications in the United States. With this as background, the paper then describes historical views, perspectives, and efforts to deal with substance misuse problems in the United States and discusses how basic, clinical, and health service research, combined with recent changes in healthcare legislation and financing, have set the stage for a more effective, comprehensive public health approach...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790490/expanding-the-health-care-pipeline-through-innovation-the-mcw-model
#16
John R Raymond, Cheryl A Maurana, Joseph E Kerschner
In 2016, the Association of American Medical Colleges projected a physician shortage in the United States of approximately 90,000; in the same year, the Wisconsin Hospital Association projected a shortage of 2,000 physicians in Wisconsin. The Medical College of Wisconsin has begun to address these shortages in three ways: 1) creation of immersive regional medical school campuses in Green Bay and Central Wisconsin, in partnership with rural serving health systems; 2) creation of rural-based psychiatry and family medicine residency programs in Green Bay and central Wisconsin; and 3) expansion of the scope of practice of pharmacists through creation of a new School of Pharmacy in collaboration with the Medical College of Wisconsin School of Medicine...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790489/discovering-new-diseases-to-accelerate-precision-medicine
#17
Calum A Macrae
A rate-limiting step in multiple areas of medicine is the limited number of discrete disorders that current technologies are able to identify. Most clinical disease entities are aggregates of large numbers of discrete biological processes that simply happen to share one or two common features. We have begun to translate a wide range of new technologies to the clinic in an effort to improve the resolution and the efficiency of bedside diagnostics with a view to improving drug trials, genetic studies, and the effectiveness of the clinician in a digital environment...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790488/ethics-and-professionalism-2016
#18
C Ronald Mackenzie
Whether a reaction to events in the clinical arena, a consequence of technological innovation, or the legitimization of the marked ethos in health care, the field of medical ethics has become a complex domain in our time. Indeed, the ubiquity of ethical dilemmas in the provision of health care is well documented with more than 99% of primary care physicians reporting ethical problems arising in the conduct of their practices (1-3). Although commentary relating to this domain has most often originated in the primary care setting, hospital-based medicine and its ethics committees are another fertile source, as is medical research...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790487/developing-therapies-for-brain-tumors-the-impact-of-the-johns-hopkins-hunterian-neurosurgical-research-laboratory
#19
REVIEW
Henry Brem, Eric W Sankey, Ann Liu, Antonella Mangraviti, Betty M Tyler
The Johns Hopkins Hunterian Neurosurgical Laboratory at the Johns Hopkins University School of Medicine was created in 1904 by Harvey Cushing and William Halsted and has had a long history of fostering surgical training, encouraging basis science research, and facilitating translational application. Over the past 30 years, the laboratory has addressed the paucity of brain tumor therapies. Pre-clinical work from the laboratory led to the development of carmustine wafers with initial US Food and Drug Administration (FDA) approval in 1996...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790486/the-role-of-aging-in-the-development-of-osteoarthritis
#20
REVIEW
Richard F Loeser
Osteoarthritis (OA) is the most common form of arthritis and a significant cause of pain and disability in older adults. Among the risk factors for OA, age is the most prominent. This review will discuss the relationship between aging and the development of OA, with a particular focus on mechanisms relevant to cartilage degeneration and the role of excessive levels of reactive oxygen species. Rather than just causing random oxidative damage, an increase in reactive oxygen species that leads to oxidative stress disrupts specific cell signaling pathways...
2017: Transactions of the American Clinical and Climatological Association
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