4,765 research outputs found

    Either on Account of Sex or Color : Policing the Boundaries of the Medical Profession During Reconstruction

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    In 1868, the American Medical Association (AMA) was asked to permit consultation with female physicians and admit them as delegates. In 1870, a delegation of Black doctors sought entrance to an Annual AMA meeting. The AMA refused entrance to both female and Black physicians. This paper argues that these meetings, and the question of inclusion for Black and female practitioners, arose out of the political climate that Reconstruction created. Expanding from previous scholarship, this paper further analyzes the role of Chicago doctor Nathan Smith Davis in the perpetuation of a white medical profession

    A commentary on the interagency symposium: 'Building a Healthier Future: A Human Capital Perspective on Health and Education', presented at the European Congress of Tropical Medicine and International Health, Liverpool, UK, October 2019.

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    Good health and nutrition during childhood and adolescence are crucial to human development yet are currently areas of significant underinvestment by the health sector. This symposium brought together multisectoral perspectives on addressing this challenge

    Advancing a methodology for implant-triggered cancer treatment with Bioorthogonal Palladium-Labile prodrugs

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    Chemotherapeutics are potent molecules capable of systematically treating cancer. As healthy tissues contain features also inherent to cancer cells, treatment often results in unwanted sideeffect. As chemotherapeutic side-effect produces significant harm and often limits optimal drug dosing, new strategies must be developed to improve treatment selectivity. A prodrug strategy provides one option to improve the selectivity of an established chemotherapeutic. By modifying a pharmaceutically active drug, interaction with biology may be functionally masked. Subsequent ‘un-masking’ the prodrug exclusively at the intended treatment site may direct treatment only to where the anticancer effect is required. This thesis progresses the novel approach of bioorthogonal organometallic (BOOM) prodrug activation. A metal catalyst and masked chemotherapeutic constitute reaction partners to provide a new strategy for intratumoural prodrug activation. Whereby the prodrug and metal catalyst are independently non-cytotoxic, in combination the prodrug undergoes catalytic activation to deliver an anticancer affect. By positioning the metal catalyst within a tumour (i.e. by microsurgery), an administered masked prodrug sensitive to catalyst-mediated activation could allow for ‘targeted’ chemotherapy localised to the tumour site. The design, synthesis and study of new BOOM prodrug candidates are reported herein. Novel protecting groups are developed to enhance drug masking to biology and subsequent catalyst-mediated activation. Prodrug screening studies are carried out in cancer cell culture models, with zebrafish and in ex vivo rodent model tumour explants. The catalyst, a palladium (Pd0) functionalised bead system, is optimised for enhanced activation, drug release and in vivo implantation. The potentially infinite generation of active chemotherapeutics exclusively in tumour would increase the efficacy of treatment whilst reducing harmful effect on healthy tissue

    Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

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    Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

    Psychosocial factors associated with outcomes of sports injury rehabilitation in competitive athletes: a mixed studies systematic review.

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    The prime focus of research on sports injury has been on physical factors. This is despite our understanding that when an athlete sustains an injury it has psychosocial as well as physical impacts. Psychosocial factors have been suggested as prognostic influences on the outcomes of rehabilitation. The aim of this work was to address the question: are psychosocial factors associated with sports injury rehabilitation outcomes in competitive athletes?Mixed studies systematic review (PROSPERO reg.CRD42014008667).Electronic database and bibliographic searching was undertaken from the earliest entry until 1 June 2015. Studies that included injured competitive athletes, psychosocial factors and a sports injury rehabilitation outcome were reviewed by the authors. A quality appraisal of the studies was undertaken to establish the risk of reporting bias.25 studies were evaluated that included 942 injured competitive athletes were appraised and synthesised. Twenty studies had not been included in previous reviews. The mean methodological quality of the studies was 59% (moderate risk of reporting bias). Convergent thematic analysis uncovered three core themes across the studies: (1) emotion associated with rehabilitation outcomes; (2) cognitions associated with rehabilitation outcomes; and (3) behaviours associated with rehabilitation outcomes. Injury and performance-related fears, anxiety and confidence were associated with rehabilitation outcomes. There is gender-related, age-related and injury-related bias in the reviewed literature.Psychosocial factors were associated with a range of sports injury rehabilitation outcomes. Practitioners need to recognise that an injured athlete's thoughts, feelings and actions may influence the outcome of rehabilitation

    Pulmonary epithelial cell-derived cytokine TGF-β1 Is a critical cofactor for enhanced innate lymphoid cell function

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    SummaryEpithelial cells orchestrate pulmonary homeostasis and pathogen defense and play a crucial role in the initiation of allergic immune responses. Maintaining the balance between homeostasis and inappropriate immune activation and associated pathology is particularly complex at mucosal sites that are exposed to billions of potentially antigenic particles daily. We demonstrated that epithelial cell-derived cytokine TGF-β had a central role in the generation of the pulmonary immune response. Mice that specifically lacked epithelial cell-derived TGF-β1 displayed a reduction in type 2 innate lymphoid cells (ILCs), resulting in suppression of interleukin-13 and hallmark features of the allergic response including airway hyperreactivity. ILCs in the airway lumen were primed to respond to TGF-β by expressing the receptor TGF-βRII and ILC chemoactivity was enhanced by TGF-β. These data demonstrate that resident epithelial cells instruct immune cells, highlighting the central role of the local environmental niche in defining the nature and magnitude of immune reactions

    Pulmonary Epithelial Cell-Derived Cytokine TGF-β1 Is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function.

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    Epithelial cells orchestrate pulmonary homeostasis and pathogen defense and play a crucial role in the initiation of allergic immune responses. Maintaining the balance between homeostasis and inappropriate immune activation and associated pathology is particularly complex at mucosal sites that are exposed to billions of potentially antigenic particles daily. We demonstrated that epithelial cell-derived cytokine TGF-β had a central role in the generation of the pulmonary immune response. Mice that specifically lacked epithelial cell-derived TGF-β1 displayed a reduction in type 2 innate lymphoid cells (ILCs), resulting in suppression of interleukin-13 and hallmark features of the allergic response including airway hyperreactivity. ILCs in the airway lumen were primed to respond to TGF-β by expressing the receptor TGF-βRII and ILC chemoactivity was enhanced by TGF-β. These data demonstrate that resident epithelial cells instruct immune cells, highlighting the central role of the local environmental niche in defining the nature and magnitude of immune reactions

    Evaluation of a whole system approach to diet and healthy weight in the east of Scotland: Study protocol

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    Obesity is a global epidemic affecting all age groups, populations and income levels across continents. The causes of obesity are complex and are routed in health behaviours, environmental factors, government policy and the cultural and built environment. Consequently, a Whole System Approach (WSA) which considers the many causes of obesity and shifts the focus away from individuals as points of intervention and puts an emphasis on understanding and improving the system in which people live in is required. This protocol describes a programme of research that will: critically evaluate the evidence for WSAs; assess longitudinally the implementation of a WSA to diet and healthy weight to explore the range of levers (drivers) and opportunities to influence relevant partnerships and interventions to target obesity in East Scotland. The programme consists of four workstreams within a mixed methods framework: 1) Systematic review of reviews of WSAs to diet and healthy weight; 2) Longitudinal qualitative process evaluation of implementing two WSAs in Scotland; 3) Quantitative and Qualitative momentary analysis evaluation of a WSA; and 4) the application of System Dynamics Modelling (SDM) methodology to two council areas in Scotland. A Public Involvement in Research group (PIRg) have informed each stage of the research process. The research programme’s breadth and its novel nature, mean that it will provide valuable findings for the increasing numbers who commission, deliver, support and evaluate WSAs to diet and healthy weight nationally and internationally
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