465 research outputs found

    The community counts: a participatory approach to social audits

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    Community matters – community responds. Yet many health planners still consider people as passive recipients of programs. Social audits respond to the voice of different stakeholders, including intended beneficiaries, in order to improve health planning and service delivery. The introductory and concluding papers of a special supplement to BioMed Central, discusses the evolution of Centro de Investigación de Enfermedades Tropicales (CIET)’s social audit methods, the lessons learned, and the way forward to the next generation of social audits

    Mutations in CIC and IDH1 cooperatively regulate 2-hydroxyglutarate levels and cell clonogenicity

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    The majority of oligodendrogliomas (ODGs) exhibit combined losses of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH1-R132H or IDH2-R172K). Approximately 70% of ODGs with 1p19q co-deletions harbor somatic mutations in the Capicua Transcriptional Repressor (CIC) gene on chromosome 19q13.2. Here we show that endogenous long (CIC-L) and short (CIC-S) CIC proteins are predominantly localized to the nucleus or cytoplasm, respectively. Cytoplasmic CIC-S is found in close proximity to the mitochondria. To study wild type and mutant CIC function and motivated by the paucity of 1p19q co-deleted ODG lines, we created HEK293 and HOG stable cell lines ectopically co-expressing CIC and IDH1. Non-mutant lines displayed increased clonogenicity, but cells co-expressing the mutant IDH1-R132H with either CIC-S-R201W or -R1515H showed reduced clonogenicity in an additive manner, demonstrating cooperative effects in our assays. Expression of mutant CIC-R1515H increased cellular 2-Hydroxyglutarate (2HG) levels compared to wild type CIC in IDH1-R132H background. Levels of phosphorylated ATP-citrate Lyase (ACLY) were lower in cell lines expressing mutant CIC-S proteins compared to cells expressing wild type CIC-S, supporting a cytosolic citrate metabolism-related mechanism of reduced clonogenicity in our in vitro model systems. ACLY or phospho-ACLY were similarly reduced in CIC-mutant 1p19q co-deleted oligodendroglioma patient samples

    Development of a multi-locus sequence typing scheme for Laribacter hongkongensis, a novel bacterium associated with freshwater fish-borne gastroenteritis and traveler's diarrhea

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    <p>Abstract</p> <p>Background</p> <p>Laribacter hongkongensis is a newly discovered, facultative anaerobic, Gram-negative, motile, sea gull-shaped rod associated with freshwater fish borne gastroenteritis and traveler's diarrhea. A highly reproducible and discriminative typing system is essential for better understanding of the epidemiology of <it>L. hongkongensis</it>. In this study, a multilocus sequence typing (MLST) system was developed for <it>L. hongkongensis</it>. The system was used to characterize 146 <it>L. hongkongensis </it>isolates, including 39 from humans and 107 from fish.</p> <p>Results</p> <p>Fragments (362 to 504 bp) of seven housekeeping genes were amplified and sequenced. Among the 3068 bp of the seven loci, 332 polymorphic sites were observed. The median number of alleles at each locus was 34 [range 22 (<it>ilvC</it>) to 45 (<it>thiC</it>)]. All seven genes showed very low <it>d</it><sub><it>n</it></sub>/<it>d</it><sub><it>s </it></sub>ratios of < 0.04, indicating that no strong positive selective pressure is present. A total of 97 different sequence types (STs) were assigned to the 146 isolates, with 80 STs identified only once. The overall discriminatory power was 0.9861. eBURST grouped the isolates into 12 lineages, with six groups containing only isolates from fish and three groups only isolates from humans. Standardized index of association (<it>I</it><sup><it>S</it></sup><sub><it>A</it></sub>) measurement showed significant linkage disequilibrium in isolates from both humans and fish. The <it>I</it><sup><it>S</it></sup><sub><it>A </it></sub>for the isolates from humans and fish were 0.270 and 0.636, indicating the isolates from fish were more clonal than the isolates from humans. Only one interconnected network (<it>acnB</it>) was detected in the split graphs. The P-value (P = 0) of sum of the squares of condensed fragments in Sawyer's test showed evidence of intragenic recombination in the <it>rho, acnB </it>and <it>thiC </it>loci, but the P-value (P = 1) of maximum condensed fragment in these gene loci did not show evidence of intragenic recombination. Congruence analysis showed that all the pairwise comparisons of the 7 MLST loci were incongruent, indicating that recombination played a substantial role in the evolution of <it>L. hongkongensis</it>. A website for <it>L. hongkongensis </it>MLST was set up and can be accessed at <url>http://mlstdb.hku.hk:14206/MLST_index.html</url>.</p> <p>Conclusion</p> <p>A highly reproducible and discriminative MLST system was developed for <it>L. hongkongensis</it>.</p

    A prospective cohort study of the long-term effects of CPAP on carotid artery intima-media thickness in Obstructive sleep apnea syndrome

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    <p>Abstract</p> <p>Objective</p> <p>To examine the long-term effect of CPAP on carotid artery intima-media thickness (IMT) in patients with Obstructive sleep apnea syndrome(OSAS).</p> <p>Methods</p> <p>A prospective observational study over 12 months at a teaching hospital on 50 patients newly diagnosed with OSAS who received CPAP or conservative treatment (CT). Carotid IMT was assessed with B-mode Doppler ultrasound from both carotid arteries using images of the far wall of the distal 10 mm of the common carotid arteries at baseline, 6 months and 12 months.</p> <p>Measurements and results [mean (SE)]</p> <p>Altogether 28 and 22 patients received CPAP and CT respectively without significant differences in age 48.8(1.8) vs 50.5(2.0)yrs, BMI 28.2(0.7) vs 28.0(1.2)kg/m2, ESS 13.1(0.7) vs 12.7(0.6), AHI 38(3) vs 39(3)/hr, arousal index 29(2) vs 29(2)/hr, minimum SaO<sub>2 </sub>75(2) vs 77(2)% and existing co-morbidities. CPAP usage was 4.6(0.3) and 4.7(0.4)hrs/night over 6 months and 1 year respectively. Carotid artery IMT at baseline, 6 months, and 12 months were 758(30), 721(20), and 705(20)micron for the CPAP group versus 760(30), 770(30), and 778(30)micron respectively for the CT group, p = 0.002.</p> <p>Among those free of cardiovascular disease(n = 24), the carotid artery IMT at baseline, 6 months and 12 months were 722(40), 691(40), and 659(30)micron for the CPAP group (n = 12) with usage 4.5(0.7) and 4.7(0.7) hrs/night over 6 months and 12 months whereas the IMT data for the CT group(n = 12) were 660(20), 685(10), and 690(20)micron respectively, p = 0.006.</p> <p>Conclusions</p> <p>Reduction of carotid artery IMT occurred mostly in the first 6 months and was sustained at 12 months in patients with reasonable CPAP compliance.</p

    New Lymphogranuloma Venereum Chlamydia trachomatis Variant, Amsterdam

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    We retrospectively conducted a study of men who have sex with men who visited the Amsterdam, the Netherlands, sexually transmitted diseases clinic from January 2002 to December 2003 and had rectal Chlamydia trachomatis infections. We found that symptomatic (73%) as well as asymptomatic (43%) patients were infected with a new C. trachomatis LGV variant

    SARS Coronavirus Detection Methods

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    Using clinical samples from patients with severe acute respiratory syndrome, we showed that the sensitivities of a quantitative reverse transcription–polymerase chain reaction (80% for fecal samples and 25% for urine samples) were higher than those of the polyclonal (50% and 5%) and monoclonal (35% and 8%) antibody-based nucleocapsid antigen capture enzyme-linked immunosorbent assays

    Loss of CIC promotes mitotic dysregulation and chromosome segregation defects

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    Background: CIC is a transcriptional repressor inactivated by loss-of-function mutations in several cancer types, including gliomas, lung cancers, and gastric adenocarcinomas. CIC alterations and/or loss of CIC activity have been associated with poorer outcomes and more aggressive phenotypes across cancer types, which is consistent with the notion that CIC functions as a tumour suppressor across a wide range of contexts. Results: Using mammalian cells lacking functional CIC, we found that CIC deficiency was associated with chromosome segregation (CS) defects, resulting in chromosomal instability and aneuploidy. These CS defects were associated with transcriptional dysregulation of spindle assembly checkpoint and cell cycle regulators. We also identified novel CIC interacting proteins, including core members of the SWI/SNF complex, and showed that they cooperatively regulated the expression of genes involved in cell cycle regulation. Finally, we showed that loss of CIC and ARID1A cooperatively increased CS defects and reduced cell viability. Conclusions: Our study ascribes a novel role to CIC as an important regulator of the cell cycle and demonstrates that loss of CIC can lead to chromosomal instability and aneuploidy in human and murine cells through defects in CS, providing insight into the underlying mechanisms of CIC's increasingly apparent role as a "pan-cancer" tumour suppressor

    A Gestão Estratégica dos Recursos Humanos nas Autarquias Locais: estudo de caso na Câmara Municipal de Cantanhede

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    Os Recursos Humanos são fundamentais para o prosseguimento da missão e dos objetivos de qualquer organização. A Gestão Estratégica dos Recursos Humanos, permite que uma organização alcance os seus objetivos, através do aumento da probabilidade de realização dos mesmos. Esta lógica de Gestão dos Recursos Humanos, revela-se como uma promessa explícita de eficácia organizacional, que pode ser alcançada pelo desenvolvimento do conjunto de práticas de RH internamente consistentes e adequadas aos contextos organizacionais. O concretizar de uma Gestão Estratégica dos Recursos Humanos nas organizações da Administração Pública, considerando a complexidade humana e o valor inerente, é uma via para o desenvolvimento a todos os níveis. Nas Câmaras Municipais, enquanto órgãos executivos de uma das formas de Autarquias Locais que é o Município, a Gestão Estratégica dos Recursos Humanos torna-se um investimento necessário para a melhoria contínua na prestação de serviços públicos. Isso, tendo em conta que a descentralização de competências da Administração Pública Central, para as Autarquias Locais, acarreta um aumento de responsabilidades e requer maior capacidade de resposta às demandas sociais. É no contexto da Administração Pública, em particular das Autarquias Locais, que se realiza o estudo de caso na Câmara Municipal de Cantanhede. O objetivo desta investigação é compreender a dinâmica do sector dos Recursos Humanos nas Autarquias Locais, sob a perspetiva da Gestão Estratégica dos Recursos Humanos, e perceber a importância que esta tem no desempenho global dessas organizações. O tipo de pesquisa que se materializa é qualitativo e exploratório, com a realização de observação direta, análise documental e entrevistas semiestruturadas. Verifica-se com este estudo, que é preocupação da Câmara Municipal de Cantanhede e do sector dos Recursos Humanos, desenvolver procedimentos estratégicos de Gestão dos Recursos Humanos. Apesar de ser um processo limitado pelos problemas relativos à atualização das carreiras, baixa remuneração, ausência de compensações e prémio de desempenho. Para que a Gestão Estratégica dos Recursos Humanos tenha efetivamente campo de ação, é preciso que a Gestão dos Recursos Humanos seja desmistificada enquanto conceito e experienciada de forma expressiva nas Autarquias Locais, em conjunto com o reforço da autonomia dessas organizações. / Human Resources are fundamental for the pursuit of the mission and goals of any organization. The Strategic Management of Human Resources allows an organization to achieve its objectives by increasing the probability of achieving them. This Human Resource Management logic is an explicit promise of organizational effectiveness that can be achieved by developing a set of HR practices that are internally consistent and appropriate to organizational contexts. The realization of a Strategic Management of Human Resources in Public Administration organizations, considering the human complexity and the inherent value, is a way for development at all levels. In the Municipal Councils, as an executive bodies of one of the forms of Local Authorities that is the Municipality, the Strategic Management of Human Resources becomes a necessary investment for the continuous improvement in the provision of public services. This, taking into account that the decentralization of competences of the Central Public Administration, for Local Authorities, entails an increase in responsibilities and requires greater capacity to respond to social demands. It is in the context of the Public Administration, in particular the Local Authorities, that the case study is carried out in Cantanhede Town Hall. The objective of this research is to understand the dynamics of the Human Resources sector in Local Authorities, from the perspective of the Strategic Management of Human Resources, and realize the importance it has in the overall performance of these organizations. The type of research that materializes is qualitative and exploratory, with direct observation, documental analysis and semi-structured interviews. It is verified with this study, that is concern of the Cantanhede Town Hall and of the Human Resources sector to develop strategic human resources management procedures. Although it is a process limited by the problems related to the updating of the careers, low remuneration, absence of compensations and performance bonus. In order for the Strategic Management of Human Resources to have an effective field of action, it is necessary that the Human Resources Management be demystified as a concept and experienced in an expressive way in Local Authorities, together with the reinforcement of the autonomy of these organizations
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