The Changing Disease-Scape in the Third Epidemiological Transition

The epidemiological transition model describes the changing relationship between humans and their diseases. The first transition occurred with the shift to agriculture about 10,000 YBP, resulting in a pattern of infectious and nutritional diseases still evident today. In the last two centuries, some populations have undergone a second transition, characterized by a decline in infectious disease and rise in degenerative disease. We are now in the throes of a third epidemiological transition, in which a resurgence of familiar infections is accompanied by an array of novel diseases, all of which have the potential to spread rapidly due to globalization

Novel paramyxoviruses in free-ranging European bats.

The zoonotic potential of paramyxoviruses is particularly demonstrated by their broad host range like the highly pathogenic Hendra and Nipah viruses originating from bats. But while so far all bat-borne paramyxoviruses have been identified in fruit bats across Africa, Australia, South America, and Asia, we describe the detection and characterization of the first paramyxoviruses in free-ranging European bats. Moreover, we examined the possible impact of paramyxovirus infection on individual animals by comparing histo-pathological findings and virological results. Organs from deceased insectivorous bats of various species were sampled in Germany and tested for paramyxovirus RNA in parallel to a histo-pathological examination. Nucleic acids of three novel paramyxoviruses were detected, two viruses in phylogenetic relationship to the recently proposed genus Jeilongvirus and one closely related to the genus Rubulavirus. Two infected animals revealed subclinical pathological changes within their kidneys, suggestive of a similar pathogenesis as the one described in fruit bats experimentally infected with Hendra virus.Our findings indicate the presence of bat-born paramyxoviruses in geographic areas free of fruit bat species and therefore emphasize a possible virus-host co-evolution in European bats. Since these novel viruses are related to the very distinct genera Rubulavirus and Jeilongvirus, a similarly broad genetic diversity among paramyxoviruses in other Microchiroptera compared to Megachiroptera can be assumed. Given that the infected bats were either found in close proximity to heavily populated human habitation or areas of intensive agricultural use, a potential risk of the emergence of zoonotic paramyxoviruses in Europe needs to be considered

Sav1 Loss Induces Senescence and Stat3 Activation Coinciding with Tubulointerstitial Fibrosis

Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor verteporfin (VP) inhibited activation of genes associated with senescence, SASPs, and activation of Stat3 as well as impeded the development of fibrosis. Collectively, our studies offer novel insights into molecular events that are linked to fibrosis development from Sav1 loss and implicate VP as a potential pharmacological inhibitor to treat patients at risk for developing CKD and TIF

On the Origin of the Treponematoses: A Phylogenetic Approach

For 500 years, controversy has raged around the origin of T. pallidum subsp. pallidum, the bacterium responsible for syphilis. Did Christopher Columbus and his men introduce this pathogen into Renaissance Europe, after contracting it during their voyage to the New World? Or does syphilis have a much older history in the Old World? This paper represents the first attempt to use a phylogenetic approach to solve this question. In addition, it clarifies the evolutionary relationships between the pathogen that causes syphilis and the other T. pallidum subspecies, which cause the neglected tropical diseases yaws and endemic syphilis. Using a collection of pathogenic Treponema strains that is unprecedented in size, we show that yaws appears to be an ancient infection in humans while venereal syphilis arose relatively recently in human history. In addition, the closest relatives of syphilis-causing strains identified in this study were found in South America, providing support for the Columbian theory of syphilis's origin

Independent Review Of Social And Population Variation In Mental Health Could Improve Diagnosis In DSM Revisions

At stake in the May 2013 publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are billions of dollars in insurance payments and government resources, as well as the diagnoses and treatment of millions of patients. We argue that the most recent revision process has missed social determinants of mental health disorders and their diagnosis: environmental factors triggering biological responses that manifest themselves in behavior; differing cultural perceptions about what is normal and what is abnormal behavior; and institutional pressures related to such matters as insurance reimbursements, disability benefits, and pharmaceutical marketing. In addition, the experts charged with revising the DSM lack a systematic. way to take population-level variations in diagnoses into account. To address these problems, we propose the creation of an independent research review body that would monitor variations in diagnostic patterns, inform future DSM revisions, identify needed changes in mental health policy and practice, and recommend new avenues of research. Drawing on the best available knowledge, the review body would make possible more precise and equitable psychiatric diagnoses and interventions

Winter 2015

Volume 2, Issue 1 Winter 2015Volumn 2, Issue 1 of the Journal of Teaching Effectiveness and student AcievementAngelo State University College of EducationInvestigating a Model of Mentoring for Effective Teaching Dr. Lori Bird and Dr. Peter Hudson…….p11 Early Career Teacher Attrition: Searching for Answers in Preservice Preparation Dr. Gloria Graham Flynn………p22 A Perceptual Assessment of Non-Traditional STEM Teacher Candidates: A University Partnership for Transition to Teaching Dr. Gail Hughes, Dr. Alicia Cotabish, Dr. Carolyn Williams, and Dr. Donna Wake…..p32 Baby It’s Cold Outside: Perspectives on Teacher Retention and Student Achievement in Artic Schools Dr. Ute Kaden………p45 Transformations to Serve English Learners: A Call for Innovative Partnerships in Educator Preparation Dr. Joan Lachance………p56 Successes and Struggles of Teaching: Perspectives of Beginning, Mid-Career, and Veteran Teachers Dr. Alyson Lavigne and Dr. Amanda Bozack………p68 Teacher Inquiry: A Foundation for Mentoring Teachers During Induction and Throughout Their Career Dr. Michele Marable, Dr. Kristin Kurtsworth--‐Keen, Dr. Kelly Harper, and Dr. Karen Dutt-Doner…….p81 Perceptions of Transformational Leadership Behavior by Secondary Principals and Teachers in Diverse and Non-Diverse Schools Dr. Fernando Valle and Dr. Gionet Cooper…..p9

Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Background: In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species, thus producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways: a) GSH is synthesized via the transsulfuration pathway, and Cys is the rate-limiting substrate; b) intermediates of the methionine cycle regulate both the transsulfuration pathway and As methylation; c) GSH serves as the electron donor for reduction of arsenate to arsenite; and d) As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys. Objectives: We tested the hypothesis that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS (i.e., a more oxidized environment). Methods: For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of five water As concentration categories: & 10 (n = 76), 10–100 (n = 104), 101–200 (n = 86), 201–300 (n = 67), and < 300 µg/L (n = 45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC. Results: An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change, –25.4 µmol/L; 95% CI: –45.3, –5.31) and plasma CySS (mean change, –3.00 µmol/L; 95% CI: –4.61, –1.40). We observed similar associations with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys. Conclusions: The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other nonprotein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine

The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis

Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug targe

A Geologic Play Book for Utica Shale Appalachian Basin Exploration

This “Geologic Play Book for Utica Shale Appalachian Basin Exploration” (hereafter referred to as the “Utica Shale Play Book Study” or simply “Study”) represents the results of a two-year research effort by workers in five different states with the financial support of fifteen oil and gas industry partners. The Study was made possible through a coordinated effort between the Appalachian Basin Oil & Natural Gas Research Consortium (AONGRC) and the West Virginia University Shale Research, Education, Policy and Economic Development Center