1,495 research outputs found

    Nontuberculous Mycobacterial Infections: Negligent and Emerging Pathogens

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    Nontuberculous mycobacteria (NTM) are a heterogeneous group of microorganisms other than Mycobacterium tuberculosis (M. tuberculosis) complex and Mycobacterium leprae. NTM infections have increased globally and are now considered an emerging infection as they are often encountered in developed countries. NTMs require extended treatment adding considerably to the economic burden. The increasing number of patients with immunocompromised disorders, increasing usage of immunosuppressive agents, general awareness of the NTM diseases due to the advancement in molecular diagnostic techniques and aging of the population increase the prevalence rate of NTM infections. However, several barriers such as the requirement of better diagnostic techniques, settled treatment guidelines, clinician awareness and knowledge of pathogenesis are limiting and NTM infections are often not treated promptly. Etiology and epidemiology of NTM infections [Mmycobacterium avium complex (slowly growing mycobacteria, SGM) and rapidly growing mycobacteria (RGM)] are discussed in this chapter. Clinical features, diagnosis and currently available treatment guidelines for these infections in skin, eye and lung are summarized. Suggestions for future research directions are suggested particularly for the better understanding of host-pathogen crosstalk and new therapeutic strategies

    Outcomes of HIV treatment from the private sector in low-income and middle-income countries: a systematic review protocol

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    Introduction: Private sector provision of HIV treatment is increasing in low-income and middle-income countries (LMIC). However, there is limited documentation of its outcomes. This protocol reports a proposed systematic review that will synthesise clinical outcomes of private sector HIV treatment in LMIC. Methods and analysis: This review will be conducted in accordance with the preferred reporting items for systematic review and meta-analyses protocols. Primary outcomes will include: (1) proportion of eligible patients initiating antiretroviral therapy (ART); (2) proportion of those on ART with 90% ART adherence (based on any measure reported); (3) proportion screened for non-communicable diseases (specifically cervical cancer, diabetes, hypertension and mental ill health); (iv) proportion screened for tuberculosis. A search of five electronic bibliographical databases (Embase, Medline, PsychINFO, Web of Science and CINAHL) and reference lists of included articles will be conducted to identify relevant articles reporting HIV clinical outcomes. Searches will be limited to LMIC. No age, publication date, study-design or language limits will be applied. Authors of relevant studies will be contacted for clarification. Two reviewers will independently screen citations and abstracts, identify full text articles for inclusion, extract data and appraise the quality and bias of included studies. Outcome data will be pooled to generate aggregative proportions of primary and secondary outcomes. Descriptive statistics and a narrative synthesis will be presented. Heterogeneity and sensitivity assessments will be conducted to aid interpretation of results. Ethics and dissemination: The results of this review will be disseminated through a peer-reviewed scientific manuscript and at international scientific conferences. Results will inform quality improvement strategies, replication of identified good practices, potential policy changes, and future research

    Capacity building of sea level and climate monitoring in the Pacific region: Fiji case study

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    In order to enhance capacity building in the Pacific region, and to raise awareness on climate change and sea level issues, teaching and training modules were made available to the Pacific community through the “South pacific sea level and climate monitoring project” funded by AusAID. Numerous training workshops have been conducted through the project since its inception in 1991 and the project is now in its fourth and final phase. It was hoped that the goals of capacity building for the stakeholders on correct information of climate change and sea level have been understood and taken heed of. In addition, “The scientific educational resources and experience associated with the deployment of Argo” (SEREAD) project was also set up especially for ocean science in the Pacific island schools in 2001. However, it has been realized that the data from this project is more relevant to tertiary level rather than to secondary level students. Consequently, a survey was carried out to gauge the students’ outlook towards the physical side of marine science. The survey revealed that more than 80% of both tertiary level and high school non-physical science students decided not to take the physical aspect of marine science sighting reasons that it is either a difficult subject, boring, too hard to understand or difficult to pass in the examination. Even amongst students taking physical science, only about 50% believe that the physical aspect of marine science is enjoyable. A minority of students at USP and high school take science as a subject and a small proportion from them take the physical science. From this scenario, it can be predicted that there will be a shortage of physical science graduates in the future. The confidence of the Pacific community in the work of scientists is built on faith. They appreciate the effect of science on their lives and support it but are unaware of the scientific methods involved. Therefore, for the sustainability of physical aspect of marine science in the future for the Pacific region, public awareness of climate change and sea level is vitally important and it should be widely promoted in the community as a matter of urgency

    Hypoglycaemia in type 2 diabetes treated with pre-mixed insulin

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    The burden of hypoglycaemia in type 2 diabetes is increasingly recognised, regardless of treatment regimen.1-3 However, time in hypoglycaemia for individuals with type 2 diabetes who use pre-mixed (biphasic) insulin remains unclear. The aim of our prospective, open-label, single arm, pilot, observational study was to determine the amount of time individuals in this cohort spent in hypoglycaemia (ISRCTN 10603608). The primary endpoint was sensor derived time in hypoglycaemia (TBR

    Comparisons on the nutritive values of local and introduced forages and feed mixture for ruminant feed in central dry zone of Myanmar

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    This study aimed to compare nutritive values of local (Sorghum) and introduced (Mombasa) forages and their feed mixtures for ruminant feed in central dry zone of Myanmar. Sorghum based feed mixtures (FeedMix-1, 2 and 3) were the commonly used feed mixtures for cattle in dry zone of Myanmar and other feed mixtures (FeedMix-4, 5 and 6) were based on Mombasa. The lower CP and higher fibre contents (P<0.05) were observed in sorghum and its feed mixtures. The highest gas volumes (P<0.05) were observed in the FeedMix-4 and 6, and then the lowest gas volume (P<0.05) was observed in FeedMix-3. The gas production from quickly soluble fraction (a) of sorghum was significantly higher (P<0.05) than that of Mombasa, inversely the gas production from insoluble fraction (b) of sorghum was significantly lower (P<0.05) than that of Mombasa. Moreover, potential gas production (a+b), ME, OMD and SCFA of sorghum were also significantly lower (P<0.05) than those of Mombasa. The value of “a” was lowest (P<0.05) in FeedMix-1, whereas the highest value was found in FeedMix-6. The lowest values (P<0.05) of “b”, “a+b”, ME, OMD and SCFA were observed in FeedMix-3 and the highest values (P<0.05) of those parameters were found in FeedMix-4. Thus, the higher nutritive values observed in the introduced forage, Mombasa and its feed mixtures were indicating that Mombasa should be used instead of sorghum for the feed of cattle in dry zone of Myanmar.&nbsp

    A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase

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    l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as the primary AEP cleavage site. Sole modification at this site rendered ASNase resistant to AEP cleavage and suggested a key role for the flexible active loop in determining ASNase activity. We therefore propose what we believe to be a novel mechanism of drug resistance to ASNase. Our results may help to identify alternative therapeutic strategies with the potential of further improving outcome in childhood ALL
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