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Santa Cruz de la Sierra, Bolivia

Halstead S.B.,Bethesda University
Vaccine | Year: 2013

A recent clinical trial of a live-attenuated tetravalent chimeric yellow fever-dengue vaccine afforded no protection against disease caused by dengue 2 (DENV-2). This outcome was unexpected as two or more doses of this vaccine had raised broad neutralizing antibody responses. Data from pre-clinical subhuman primate studies revealed that vaccination with the monotypic DENV-2 component failed to meet established criteria for solid protection to homotypic live virus challenge. Accordingly, it is suggested that preclinical testing adopt more rigorous criteria for protection and that Phase I testing be extended to require evidence of solid monotypic protective immunity for each component of a dengue vaccine by direct challenge with live-attenuated DENV. Because live-attenuated tetravalent DENV vaccines exhibit evidence of immunological interference phenomena, during Phase II, volunteers given mixtures of DENV 1-4 vaccines should be separately challenged with monotypic live-attenuated DENV. Immune responses to live-attenuated challenge viruses and vaccine strains should be studied in an attempt to develop useful in vitro correlates of in vivo protection. Finally, it will be important to learn if DENV non-structural protein 1 (NS1) contributes to pathogenesis of the vascular permeability syndrome in humans. If so, immunity to dengue 1-4 NS1 may be crucial to prevent severe disease. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved. Source


Halstead S.B.,Bethesda University
Vaccine | Year: 2013

A recent clinical trial of a live-attenuated tetravalent chimeric yellow fever-dengue vaccine afforded no protection against disease caused by dengue 2 (DENV-2). This outcome was unexpected as two or more doses of this vaccine had raised broad neutralizing antibody responses. Data from pre-clinical subhuman primate studies revealed that vaccination with the monotypic DENV-2 component failed to meet established criteria for solid protection to homotypic live virus challenge. Accordingly, it is suggested that preclinical testing adopt more rigorous criteria for protection and that Phase I testing be extended to require evidence of solid monotypic protective immunity for each component of a dengue vaccine by direct challenge with live-attenuated DENV. Because live-attenuated tetravalent DENV vaccines exhibit evidence of immunological interference phenomena, during Phase II, volunteers given mixtures of DENV 1-4 vaccines should be separately challenged with monotypic live-attenuated DENV. Immune responses to live-attenuated challenge viruses and vaccine strains should be studied in an attempt to develop useful in vitro correlates of in vivo protection. Finally, it will be important to learn if DENV non-structural protein 1 (NS1) contributes to pathogenesis of the vascular permeability syndrome in humans. If so, immunity to dengue 1-4 NS1 may be crucial to prevent severe disease. © 2013 The Author. Source


Kirkpatrick B.D.,University of Vermont | Tribble D.R.,Bethesda University
Current Opinion in Gastroenterology | Year: 2011

Purpose of review The present review will update the reader to the clinical, epidemiological and immunologic advances in the field of human campylobacteriosis. Recent findings New advances in human campylobacteriosis include an increased appreciation of the role of Campylobacter jejuni in postinfectious sequelae, a broadened understanding of Campylobacter-associated disease burden and the interplay between host immunity and bacterial factors. Antibiotic management has also become more complex: C. jejuni has undergone a rapid increase in resistance to the fluoroquinolone antibiotics and concurrently, postinfectious irritable bowel syndrome has been associated with a longer duration of untreated infection. In anticipation of new candidate C. jejuni vaccines, progress in understanding human immune responses to infection has been made via human experimental infections. These tightly controlled studies have also increased our understanding of the natural history of campylobacteriosis as well as observations of recrudescent infection following treatment with C. jejuni-sensitive antibiotics. Summary As one of the most common agents of bacterial gastroenteritis and a major health burden for both developing world and industrialized nations, Campylobacter infections remain a high priority for research efforts to improve prevention and management. Priorities for the future include vaccine development, pathogen-specific immunity and identification of risk factors for postinfectious sequelae. © 2010 Wolters Kluwer Health. Source


Schell M.J.,Bethesda University
Cellular and Molecular Life Sciences | Year: 2010

The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure. Inositol trisphosphate [Ins(1,4,5)P 3] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P 3. These enzymes terminate the signal to release Ca2+ from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P 4]. Independent of their enzymatic activity, ITPKs regulate the microstructure of the actin cytoskeleton. The immune phenotypes of ITPK knockout mice raise new questions about how ITPKs control inositol phosphate lifetimes within spatial and temporal domains during lymphocyte maturation. The intense concentration of ITPK on actin inside the dendritic spines of pyramidal neurons suggests a role in signal integration and structural plasticity in the dendrite, and mice lacking neuronal ITPK exhibit memory deficits. Thus, the molecular and anatomical features of ITPKs allow them to regulate the spatiotemporal properties of intracellular signals, leading to the formation of persistent molecular memories. © 2010 Birkhäuser Verlag. Source


Stephens M.B.,Bethesda University
Journal of the American Board of Family Medicine | Year: 2011

Introduction: Obesity is the leading health problem in the United States. Providers often fail to document obesity in patients whose body mass index (BMI) is more than 30. Methods: Using a structured data query of the military health system electronic medical record, we determined the BMI and presence of an associated International Classification of Disease code in a cohort of more than 3 million patients. Results: Fifteen percent of patients (482,628) had a BMI exceeding 30. Of those patients with a BMI more than 30, 78,776 (16%) had an associated International Classification of Disease 9 code documenting obesity in their record. Conclusion: Coding and documentation of obesity is inadequate. This has implications for delivery of preventive counseling and efforts to mitigate rising trends in obesity. Source

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