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Transactions of the American Clinical and Climatological Association

Mark E Rosenberg
The medical education continuum spans undergraduate medical education (i.e., medical school), graduate medical education (i.e., residency and fellowship), and continuing medical education. This article provides three examples across the medical education and practice continuum where an outcomes-based approach is being used. By focusing on outcomes instead of process, a more predictable product of undergraduate medical education will be a medical student capable on day 1 of performing the work required of residency...
2018: Transactions of the American Clinical and Climatological Association
Sherita Hill Golden
As young physicians, we are trained to listen to our patients as they relay a set of signs, symptoms, and feelings to us, and then to translate their stories into a diagnosis and treatment plan that improves their health status and overall quality of life. The art of storytelling is crucial in disseminating diverse and innovative perspectives in academic medicine. First, stories from patients play a pivotal role in defining new areas of research focus for building the careers of physician-scientists, allowing them to take full advantage of the depth and breadth of their clinical and research skills...
2018: Transactions of the American Clinical and Climatological Association
Marvin A Konstam
We are presently seeing exponential advances in medical knowledge and development of therapeutic and diagnostic tools. We have also begun to experience an historic restructuring of our health care system. But health care costs continue to rise, disparities persist, and the chaotic, disjointed, and often thoughtless discourse in Washington threatens to roll back the prior advances. Improvement in patient care will be severely stymied if the threats to academic medical centers are not countered. This paper will explore our present state through the lens of cardiovascular care...
2018: Transactions of the American Clinical and Climatological Association
Harry P Selker, Sheeona Gorman, Kenneth I Kaitin
Efficacy trials, which assess treatments in optimally selected patients under advantageous conditions for relatively short time periods, are necessary to gain regulatory approval for marketing. In contrast, effectiveness trials, which test treatments across a spectrum of patients in real-world conditions with follow-up periods that match typical treatment regimens, provide critical information on drug effects in those patients who may ultimately receive the treatment. We previously proposed a study design that integrates efficacy and effectiveness trials into a 2-component "efficacy-to-effectiveness (E2E) trial," in which if the initial efficacy trial component is positive, then the trial immediately and seamlessly transitions to the effectiveness trial component...
2018: Transactions of the American Clinical and Climatological Association
E Dale Abel
Mitochondria are the metabolic powerhouses of cells. In addition to generating adenosine triphosphate (ATP), they play important roles in cell survival pathways such as apoptosis and necrosis. Mitochondrial size and shape are dynamically regulated by a process known as mitochondrial dynamics. The significance of this process in metabolically active cells such as skeletal and cardiac muscle are only now beginning to be elucidated. In cardiac muscle, mitochondrial dynamics plays an important role in mitochondrial quality control and defects in regulatory pathways that govern these processes and leads to heart failure...
2018: Transactions of the American Clinical and Climatological Association
Ronald G Crystal, Odelya E Pagovich
Advances in understanding the immunological basis and mechanisms underlying allergic and immunologic disorders have led to effective but costly long-term and repetitive biologic therapies. Gene therapy is a rapidly advancing technology, in which a single administration of an adeno-associated virus encoding the therapeutic protein or monoclonal antibody may provide effective long-term therapy for allergic and immunologic disorders. In this review, we summarize the recent studies from our laboratory developing gene therapy strategies to treat hereditary angioedema and peanut allergy...
2018: Transactions of the American Clinical and Climatological Association
Elizabeth O Ofili, Priscilla E Pemu, Alexander Quarshie, Ernest Alema Mensah, Latrice Rollins, Folake Ojutalayo, Atuarra McCaslin, Bethany Saint Clair
Health 360x is a mobile health application and social platform that integrates self-monitoring and decision support for preventive health. We studied 240 diabetic patients in primary care practices and a church community in metropolitan Atlanta. Health coaches were trained on the Health 360x curriculum, which was adapted from the American Association of Diabetes Educators. Participants worked with the health coaches to set goals for diabetes self-management. The intervention included weekly coaching for 12 weeks and online peer networking...
2018: Transactions of the American Clinical and Climatological Association
Sumanth D Prabhu
The role of innate and adaptive immunity in heart failure (HF) is poorly understood. We discovered that mice with ischemic HF exhibit robust expansion of proinflammatory monocytes/macrophages, classical and plasmacytoid dendritic cells, and CD4+ and CD8+ T cells. There was profound splenic remodeling indicative of heightened antigen processing, and expanded antigen-experienced effector and memory CD4+ T cell populations. A series of subsequent studies in HF mice that incorporated splenectomy, adoptive transfer of both unselected splenocytes and splenic CD4+ T-cells, and antibody-mediated CD4+ T-cell depletion indicated that intensely activated splenic immune cells: 1) underlie the chronic inflammatory response in HF, 2) traffic and home to the failing heart, and 3) exhibit immune memory and are primed to induce tissue injury that promotes pathological cardiac remodeling...
2018: Transactions of the American Clinical and Climatological Association
Phyllis A Dennery, Jennifer Carr, Abigail Peterson, Hongwei Yao
In premature neonates, hyperoxic exposure contributes to lung injury characterized by simplified alveolarization and arrested vascularization. These are the hallmarks of bronchopulmonary dysplasia, a disease with long-term consequences on pulmonary and neurodevelopmental function. Lung vascular development and endothelial cell signals are synergistically important for normal alveolarization. It has been shown that metabolism of nutrients such as glucose, fatty acid, and glutamine is key in controlling proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses, which contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia...
2018: Transactions of the American Clinical and Climatological Association
Barry London, Alexander M Greiner, Haider Mehdi, Rebecca Gutmann
Inherited conditions that lead to cardiac arrhythmias and sudden cardiac death remain an important cause of morbidity and mortality. Identifying the genes responsible for these rare conditions can provide insights into the more common and heritable forms of sudden cardiac death seen in patients with structural heart disease. We and others have used candidate gene approaches and positional cloning in large families to show that mutations in ion channels and ion channel related proteins cause familial arrhythmia syndromes including long QT and Brugada syndromes...
2018: Transactions of the American Clinical and Climatological Association
Gary S Firestein
Rheumatoid arthritis is a synovial inflammatory disease marked by joint infiltration by immune cells and damage to the extracellular matrix. Although genetics plays a critical role in heritability and its pathogenesis, the relative lack of disease concordance in identical twins suggests that noncoding influences can affect risk and severity. Environmental stress, which can be reflected in the genome as altered epigenetic marks, also contributes to gene regulation and contributes to disease mechanisms. Studies on DNA methylation suggest that synovial cells, most notably fibroblast-like synoviocytes, are imprinted in rheumatoid arthritis with epigenetic marks and subsequently assume an aggressive phenotype...
2018: Transactions of the American Clinical and Climatological Association
James O Woolliscroft, Cyril Grum
Medical practitioners routinely use dual process clinical reasoning: pattern recognition, termed system 1 thinking, and system 2 thinking or analytic reasoning. System 1 thinking, a hallmark of expertise developed through experience with multiple similar patients and deliberate practice, is rapid and automatic. For decades, the structured written medical write-up and progress notes served an educational as well as a patient care role. The introduction of electronic health records (EHRs) potentially hinders the development of the cognitive models upon which system 1 thinking is predicated...
2018: Transactions of the American Clinical and Climatological Association
Steven Grinspoon
Cardiovascular disease (CVD) rates are 50% to 100% higher in human immunodeficiency virus (HIV) patients. Traditional risks account for only 25% of this excess risk. Excess CVD risk in HIV may relate in part to increases in ectopic adipose depots. CVD in HIV-infection is characterized by atypical highly vulnerable plaque lesions, which are inflamed, in tight relationship to immune, and monocyte activation pathways. Using 18 fluorine-2-deoxy-D-glucose positron-emission tomography imaging techniques, we have shown increased arterial inflammation which persists even after effective antiretroviral therapy...
2018: Transactions of the American Clinical and Climatological Association
David J Pinsky
A common thread underlying vascular or tissue injury is the loss of plasmalemmal integrity and the passive (or even active) spillage of intracellular contents into the circulation. Purinergic nucleotides, which serve as energy shuttling moieties within cells, are among the contents released into the bloodstream, where they signal danger and trigger thrombosis and inflammation. To regain vascular homeostasis, vascular cells have evolved highly conserved mechanisms to transact the catalytic degradation of extracellular nucleotides such as adenosine triphosphate (ATP) and adenosine diphosphate (ADP)...
2018: Transactions of the American Clinical and Climatological Association
Jonathan A Epstein
In the nucleus of all cells, DNA is packaged in association with histone proteins to form chromatin. It is becoming increasingly clear that the organization of chromatin in three dimensions within the nucleus is highly regulated and can contribute to gene expression and cell function. The regions of the genome that are near the nuclear periphery are termed "lamin associated domains" or LADs (1-3). Here, I present a theory, based on recent results, for "chromatin competence" in which the organization of LADs in a progenitor cell accounts for the ability of that cell to respond to external factors to promote differentiation into one lineage or another...
2018: Transactions of the American Clinical and Climatological Association
Theodora Ross
The new genetics, defined as that which followed the completion of the human genome project and includes development of rapid and cheaper next-generation sequencing (NGS), is impacting our medical world in several ways (1). As is the case in any new area of medicine, the field is infused with "truthiness," where instead, what is needed for good patient care and scientific rigor is an effort to close in on the truth. Today, I'll discuss how variation in the human genome is being evaluated and re-evaluated as we sequence more and more of our patients' genes...
2018: Transactions of the American Clinical and Climatological Association
Julie Ann Freischlag
This review describes the outcomes for patients who underwent first rib resection for all three forms of thoracic outlet syndrome during a period of 10 years. The data were previously published in 2014 and the ACCA presentation, and this manuscript are derived largely from this work (1). Patients treated with first rib section from August 2003 through July 2013 were retrospectively reviewed using a prospectively maintained database. Five hundred thirty-eight patients underwent 594 first rib resections for indications of neurogenic (n = 308, 52%), venous (n = 261, 44%), and arterial (n = 25, 4%)...
2018: Transactions of the American Clinical and Climatological Association
Elizabeth J Phillips
Preventive efforts for serious immunologically mediated adverse drug reactions (IM-ADRs) have been fueled by discovery of strong class I human leukocyte antigen (HLA) associations; however, the low positive predictive value of HLA for IM-ADRs has limited translation. Studies were undertaken to explain why most patients carrying an HLA risk allele do not develop IM-ADR on exposure to the risk drug. Tissue-specific approaches defined the T-cell receptor (TCR) repertoire and phenotype of the pathogenic T cells found in the skin and blister fluid of IM-ADRs...
2018: Transactions of the American Clinical and Climatological Association
Jeanne M Marrazzo
Although great progress has been made in treating HIV-1 infection globally, incidence remains high in many locales, especially sub-Saharan Africa. Two-thirds of the burden of disease is there, and among those infected, 60% are women. Pre-exposure prophylaxis, the administration of a drug to prevent acquisition of infection, has proven to be a promising prevention modality for HIV-1 when administered as a daily oral regimen of tenofovir disoproxil fumarate/emtricitabine. However, data suggest that oral tenofovir disoproxil fumarate/emtricitabine may not achieve protective concentrations in the cervicovaginal tissue as rapidly as it does in the rectum...
2018: Transactions of the American Clinical and Climatological Association
Eric R Fearon
Colorectal cancers (CRCs) harbor accumulated defects in key signaling pathways that regulate cell phenotypes, including proliferation, survival, metabolism, and differentiation. To study the functional contributions of the accumulated molecular defects in CRC, we have developed approaches to inactivate selected tumor suppressor and/or activate oncogenes in mouse colon epithelium. Conditional inactivation of the CDX2 tumor suppressor protein in conjunction with oncogenic activation of the BRAF protein promotes development of serrated glandular benign and malignant tumors in the mouse colon...
2018: Transactions of the American Clinical and Climatological Association
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