310 research outputs found

    Implementing asset-based community development : a case study from the Philippines : a thesis presented in partial fulfilment of the requirements for the degree of Master of Philosophy in Development Studies at Massey University

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    Within the alternative development paradigm, needs-based models have been critiqued for the part they play in accentuating local deficiency and thereby increasing dependency on externally-driven development. The asset-based approach to community development (ABCD) has been presented as a capacities-focused alternative, aimed at establishing community-driven development and promoting authentic local empowerment. This thesis presents a case study into ABCD as it has been applied in a developing country context, analysing it in relationship to some of the theoretical premises of the approach and the wider development literature. The research, undertaken on the island of Mindanao in the Philippines, describes how the ABCD model was implemented and adapted to local circumstances. The findings indicate that the ABCD intervention resulted in improvements within the case study community, particularly pertaining to the expansion of community facilities, livelihood choices, household incomes, individual and collective motivation, and community pride. Overall, this study endorses ABCD as an effective approach to development in the developing world, while at the same time highlighting issues associated with its implementation. Questions are also raised regarding three global development themes that emerged in the course of the study, namely the development of capacity, the management of social process and the meaning of empowerment

    When and how to treat acute hepatitis C?

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    Background: Appropriate treatment of acute hepatitis C is still a matter of controversy due to the lack of large controlled trials. Aim: To assess the effectiveness of interferon as treatment for acute hepatitis C by meta-analysis. Methods: MEDLINE search (1985-2002) was supplemented with manual searches of reference lists. Studies were included if they were controlled trials comparing interferon to no treatment and if they included patients with either post-transfusion or sporadic acute hepatitis C. Twelve trials were analyzed (414 patients). The outcome assessed was the sustained virological response (SVR) rate (undetectable hepatitis C virus RNA in serum at least 6 months after cessation of therapy). Results: Interferon significantly increased the SVR (risk difference 49%; 95% confidence interval 32.9-65%) in comparison to no treatment. The risk difference of SVR increased from 5 to 90% when trials were ordered by increasing interferon weekly dose. Delaying therapy by 8-12 weeks after the onset of disease does not compromise the SVR rate. Conclusions: Current evidence is sufficient to recommend interferon treatment of patients with acute hepatitis C. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during the 1st month is the best option of treatment. © 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

    The importance of the interactions between KIRs and HLA ligands in the development of human autoimmune and viral diseases

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    Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain KIR/HLA combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIR profiles may be detrimental in autoimmune pathogenesis, and specific KIR genes may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. Here we reviewed a growing body of evidence purporting the influence of KIR polymorphism and KIR-HLA interaction in the development of the main human autoimmune and viral diseases

    Endocrine disorders in childhood and adolescence. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review.

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    OBJECTIVE: Subclinical hypothyroidism (SH) is quite common in children and adolescents. The natural history of this condition and the potential effects of replacement therapy need to be known to properly manage SH. The aim of this review is to analyse: 1) the spontaneous evolution of SH, in terms of the rate of reversion to euthyroidism the persistence of SH or the progression to over hypothyroidism; 2) the effects of replacement therapy, with respects to auxological data, thyroid volume and neuropsychological functions. Methods: We systematically searched PubMed, Cochrane and EMBASE (1990 to 2012) and identified 39 potentially relevant articles of which only 15 articles were suitable to be included. Results and Conclusions: SH in children is a remitting process with a low risk of evolution toward overt hypothyroidism. Most of the subjects reverted to euthyroidism or remained SH, with a rate of evolution toward overt hypothyroidism ranging between 0% to 28.8%, being 50% in only one study (9 articles). The initial presence of goiter and elevated thyroglobulin-antibodies, the presence of coeliac disease and a progressive increase in thyroperoxidase-antibodies and TSH value predict a progression toward overt hypothyroidism. Replacement therapy is not justified in children with SH but with TSH 5-10 mIU/L, no goiter and negative anti-thyroid antibodies. An increased growth velocity was shown in children treated with levothyroxine (2 articles). Levothyroxine reduced thyroid volume in 25% to 100% of children with SH and autoimmune thyroiditis (2 studies). No effects on neuropsychological functions (one study) and post-treatment evolution of SH (one study) were reported

    Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway.

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    Abstract BACKGROUND/AIMS: Unresponsiveness to IFN-alpha is common in chronic hepatitis C. Since conditions associated with an increased oxidative stress (advanced age, steatosis, fibrosis, iron overload, and alcohol consumption) reduce the likelihood of response, we hypothesized that oxidative stress may affect the antiviral actions of IFN-alpha. METHODS: We examined in a human hepatocellular carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a generator of oxidative stress, on the IFN-alpha signaling pathway. RESULTS: Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. The reduced expression of these genes was associated to H2O2 -mediated suppression of the IFN-alpha-induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFN-alpha-inducible genes. This was accomplished by preventing the IFN-alpha-induced tyrosine phosphorylation of STAT-1 and STAT-2 through the inactivation of the upstream receptor associated tyrosine kinases, JAK-1 and Tyk-2. The suppression was fast, occurring within 5mins of pretreatment with H2O2, and did not require protein synthesis. CONCLUSIONS: In conclusion, oxidative stress impairs IFN-alpha signaling and might cause resistance to the antiviral action of IFN-alpha in chronically HCV infected patients with high level of oxidative stress in the liver

    GM Allotypes and COVID-19. A Pilot Study Performed on Sicilian Patients

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    Several studies suggest that genetic variants that influence the onset, maintenance and resolution of the immune response might be fundamental in predicting the evolution of COVID-19. In the present paper, we analysed the distribution of GM allotypes (the genetic markers of immunoglobulin Îł chains) in symptomatic and asymptomatic COVID-19 patients and in healthy controls, all born and residing in Sicily. Indeed, the role played by GM allotypes in immune responses and infection control is well known. Our findings show that the GM23 allotype is significantly reduced in healthy controls. Interestingly, in a previous study, Sicilians carrying the GM23 allotype were associated with the risk of developing a symptomatic Human Cytomegalovirus infection. However, a note of caution should be considered, due to the small sample size of patients and controls

    RemodulinÂź Pump Failure: An Emergency Medicine Simulation Scenario

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    Pulmonary hypertension (PH) is a progressive disease that causes high patient mortality. With limited hemodynamic reserve, many PH patients require maintenance IV infusion medications to maintain their activities of daily living. One common delivery method for this targeted therapy is through a RemodulinÂź (treprostinil) pump. When presenting for emergent evaluation, decompensating PH patients have a broad differential diagnosis including pump failure. PH patients are at a high risk of poor patient outcomes given the difficulty in recognizing PH-specific symptoms and unique aspects of their management. Therefore, learners will benefit from participating in an immersive simulation-based PH patient scenario in a safe learning environment. Here, we present a simulated scenario of a decompensating PH patient on a RemodulinÂź pump

    HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus

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    Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR = 3.36; 95% CI = 1.46-7.74; p = .005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR = 6.47, 95% CI = 2.58-16.26; p < .0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR = 7.06, 95% CI = 0.07-2.19; p = .002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38 ± 28.49 Όmol/L) compared to SLE patients HLA-C1 negative (108.37 ± 86.09 Όmol/L) (p = .03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients

    Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

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    <div><p>Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in <i>Cftr<sup>F508del</sup></i> homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the <i>F508del-CFTR</i> mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from <i>F508del</i> homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both <i>in vivo</i>, in mice, and <i>in vitro</i>, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 <i>F508del-CFTR</i> homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells <i>in vivo</i>, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of <i>TNF/TNF-alpha (tumor necrosis factor)</i> and <i>CXCL8</i> (<i>chemokine [C-X-C motif] ligand 8</i>) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the <i>F508del-CFTR</i> mutation.</p></div

    Death notiïŹcation: a digital communication platform for simulated patient-based training with medical students

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    This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Medical simulation experiences, focused on enhancing essential communication skills, provide high value to trainees. These communication-based simulations often require little equipment and instead use trained faculty facilitators who can impart clinical significance and expertise to trainees. Teaching communication skills and techniques remotely is theoretically possible but has been largely unexplored in medical education.1 The COVID-19 pandemic and the subsequent restrictions imposed by shelter-in-place orders and social distancing created a need to expand traditional training methods and experiment with remote simulation training for communication skills. In this brief report, we explore the experience, outcomes and barriers to implementing a simulated communication skill curriculum focused on death notification to a cohort of remote medical students
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