204 research outputs found

    Resource manual 06 - animal health and GITA : training, facilitating and communicating with communities and households for animal health workers and trainers working with the livestock vaccine value chain in Karamoja Sub Region, Uganda

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    This manual is part of a series of resource manuals to be used by those who work with animal health workers to become change agents in communities that increase the use of livestock vaccines through using a gendered intersectional transformative approach (GITA).Bill & Melinda Gates Foundation (BMGF)Global Affairs Canada (GAC

    Resource manual 06 - animal health and GITA : training, facilitating and communicating with communities and households for animal health workers and trainers working with the livestock vaccine value chain in Nepal

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    This manual is part of a series of resource manuals to be used by those who work with animal health workers to become change agents in communities that increase the use of livestock vaccines through using a gendered intersectional transformative approach (GITA).Bill & Melinda Gates Foundation (BMGF)Global Affairs Canada (GAC

    The microbiota and autoimmunity: their role in thyroid autoimmune diseases

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    Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject

    Gender and social inclusion training for vet and animal health service providers

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    In Uganda, the majority of rural households are engaged in livestock rearing. Livestock is reared by both men and women, and in some pastoral communities, sick animals are left in the care of women while men take healthy animals for grazing. Research shows that gender and attitudes of animal health service providers can affect their veterinary practice and quality of care. Developing an understanding of how gender and perceptions of it can influence veterinary practices is essential to improve the reach and quality of service delivery. However, veterinarians, animal husbandry officers, and community animal health workers, referred to as animal health service providers in this brief, often receive limited and inconsistent training. Moreover, the training does not integrate gender responsive communication and entrepreneurship skills to help animal health service providers deliver gender equitable and inclusive services.Global Affairs CanadaBill & Melinda Gates Foundatio

    Who has access to livestock vaccines? : using the social-ecological model and intersectionality frameworks to identify the social barriers to peste des petits ruminants vaccines in Karamoja, Uganda

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    Results of the study show there are seven intersecting factors that influence access to vaccination: gender, ethnicity, geographic location, age, physical ability, marital status, and access to education. The socio-ecological model (SEM) highlights vast inequalities within the current system. Access to vaccines and information about animal health was the most limited among women, widows, the elderly, the disabled, those geographically isolated, and others with pre-existing unfavorable knowledge regarding vaccination practices. Cultural norms of communities were also important factors determining access to peste des petits ruminants (PPR) vaccines. Women remain burdened with household chores, along with gender-based violence and discriminatory beliefs and practices

    TPOAb and thyroid function are not associated with breast cancer outcome: evidence from a large-scale study using data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001)

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    Background: Small-scale studies correlated the presence of thyroid autoimmunity with both improved or worsened breast cancer outcome. Objectives: We aimed to clarify this association in a large cohort using the phase III, randomized, controlled Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). Methods: TACT women >18 years old with node-positive or high-risk node-negative early breast cancer (pT1–3a, pN0–1, M0), with stored plasma (n = 1,974), taken 15.5 (median; IQR 7.0–24.0) months after breast surgery were studied. Patients had also received chemotherapy (100%), radiotherapy (1,745/1,974; 88.4%), hormonal therapy (1,378/ 1,974; 69.8%), or trastuzumab (48/1,974; 2.4%). History of thyroid diseases and/or related treatments was not available. The prognostic significance of autoantibodies to thyroid peroxidase (TPOAb; positive ≥6 kIU/L), free-thyroxine and thyrotropin (combined: euthyroid, hypothyroid, hyperthyroid) was evaluated for disease-free survival (DFS), overall-survival (OS), and time-to-recurrence (TTR), with Cox regression models in univariate and multivariable analyses. The extended median follow-up was 97.5 months. Results: No difference in DFS was found by TPOAb status (unadjusted hazard ratio [HR]: 0.97, 95%CI: 0.78–1.19; p = 0.75) and/or thyroid function (unadjusted HR [hypothyroid vs. euthyroid]: 1.15, 95% CI: 0.79–1.68; p = 0.46; unadjusted HR [hyperthyroid vs. euthyroid]: 1.14, 95% CI: 0.82–1.61; p = 0.44). Similar results were obtained for OS, TTR, multivariable analyses, when TPOAb titre by tertiles was considered, and in a subgroup of 123 patients with plasma collected before adjuvant treatments. Conclusions: No evidence for a prognostic role of TPOAb and/or thyroid function in moderate-to-high-risk early breast cancer was found in the largest and longest observational study to date

    New insights into the pathogenesis and nonsurgical management of Graves orbitopathy

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    Graves orbitopathy, also known as thyroid eye disease or thyroid-associated orbitopathy, is visually disabling, cosmetically disfiguring and has a substantial negative impact on a patient’s quality of life. There is increasing awareness of the need for early diagnosis and rapid specialist input from endocrinologists and ophthalmologists. Glucocorticoids are the mainstay of treatment; however, recurrence occurs frequently once these are withdrawn. Furthermore, in >60% of cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required. Clinical trials have shown that considerable benefit can be derived from the addition of antiproliferative agents (such as mycophenolate or azathioprine) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab, which reduces proptosis, rituximab (anti-CD20), which reduces inflammation, and tocilizumab, which potentially benefits both of these parameters. Other strategies such as orbital radiotherapy have had their widespread role in combination therapy called into question. The pathophysiology of Graves orbitopathy has also been revised with identification of new potential therapeutic targets. In this Review we provide an up-to-date overview of the field, outline the optimal management of Graves orbitopathy and summarize the research developments in this area to highlight future research questions and direct future clinical trials

    Role of hyaluronan in human adipogenesis : evidence from in-vitro and in-vivo studies

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    Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity

    Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves’ disease and orbitopathy

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    Graves’ Disease (GD) is an autoimmune condition in which thyroid-stimulating antibodies (TRAB) mimic thyroid-stimulating hormone function causing hyperthyroidism. 5% of GD patients develop inflammatory Graves’ orbitopathy (GO) characterized by proptosis and attendant sight problems. A major challenge is to identify which GD patients are most likely to develop GO and has relied on TRAB measurement. We screened sera/plasma from 14 GD, 19 GO and 13 healthy controls using high-throughput proteomics and miRNA sequencing (Illumina’s HiSeq2000 and Agilent-6550 Funnel quadrupole-time-of-flight mass spectrometry) to identify potential biomarkers for diagnosis or prognosis evaluation. Euclidean distances and differential expression (DE) based on miRNA and protein quantification were analysed by multidimensional scaling (MDS) and multinomial regression respectively. We detected 3025 miRNAs and 1886 proteins and MDS revealed good separation of the 3 groups. Biomarkers were identified by combined DE and Lasso-penalized predictive models; accuracy of predictions was 0.86 (±0:18), and 5 miRNA and 20 proteins were found including Zonulin, Alpha-2 macroglobulin, Beta-2 glycoprotein 1 and Fibronectin. Functional analysis identified relevant metabolic pathways, including hippo signaling, bacterial invasion of epithelial cells and mRNA surveillance. Proteomic and miRNA analyses, combined with robust bioinformatics, identified circulating biomarkers applicable to diagnose GD, predict GO disease status and optimize patient management
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