1,596 research outputs found

    Dissipated energy in undrained cyclic triaxial tests

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    Energy-based methods are an emerging tool for the evaluation of liquefaction potential. These methods relate excess pore water pressure build-up to seismic energy dissipated per unit volume. Further development of these methods require their validation through laboratory testing. In this paper, a comprehensive study of energy dissipated during cyclic triaxial tests is undertaken. Results of undrained cyclic triaxial tests performed on air-pluviated samples of Hostun sand prepared with different initial densities and subjected to several confining pressures and loading amplitudes are presented. The energy dissipated per unit volume is estimated from the experimental results and correlated to the generated excess pore water pressure. The correlation between those quantities appear to be independent of the initial relative density of the sample, isotropic consolidation pressure and cyclic stress ratio used in the tests. Moreover, the relationship between observed doubleamplitude axial strain and the energy dissipated per unit volume is examined. It is found that this relationship is greatly dependent on the relative density of the sample

    A Luciferase-expressing Leishmania Braziliensis Line That Leads To Sustained Skin Lesions In Balb/c Mice And Allows Monitoring Of Miltefosine Treatment Outcome

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    Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Leishmania braziliensis is the most prevalent species isolated from patients displaying cutaneous and muco-cutaneous leishmaniasis in South America. However, there are difficulties for studying L. braziliensis pathogenesis or response to chemotherapy in vivo due to the natural resistance of most mouse strains to infection with these parasites. The aim of this work was to develop an experimental set up that could be used to assess drug efficacy against L. braziliensis. The model was tested using miltefosine. Methodology/Principal Findings A L. braziliensis line, originally isolated from a cutaneous leishmaniasis patient, was passaged repeatedly in laboratory rodents and further genetically manipulated to express luciferase. Once collected from a culture of parasites freshly transformed from amastigotes, 10(6) wild type or luciferase-expressing stationary phase promastigotes were inoculated subcutaneously in young BALB/c mice or golden hamsters. In both groups, sustained cutaneous lesions developed at the site of inoculation, no spontaneous self-healing being observed 4 months post-inoculation, if left untreated. Compared to the wild type line features, no difference was noted for the luciferase-transgenic line. Infected animals were treated with 5 or 15 mg/kg/day miltefosine orally for 15 days. At the end of treatment, lesions had regressed and parasites were not detected. However, relapses were observed in animals treated with both doses of miltefosine. Conclusions/Significance Here we described experimental settings for a late-healing model of cutaneous leishmaniasis upon inoculation of a luciferase-expressing L. braziliensis line that can be applied to drug development projects. These settings allowed the monitoring of the transient efficacy of a short-term miltefosine administration.10Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2011/20484-7, 2015/09080-2]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil [473343/2012-6]CNPqFAPESP [2012/14629-5, 2015/05130-5, 2011/219702, 2011/18858-6]Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

    Validation of the Portuguese version of impulsive-premeditated aggression scale in an inmate population

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    Aggression is one of the core symptoms of antisocial personality disorder (ASPD) with therapeutic and prognostic relevance. ASPD is highly prevalent among inmates, being responsible for adverse events and elevated direct and indirect economic costs for the criminal justice system. The Impulsive/Premeditated Aggression Scale (IPAS) is a self-report instrument that characterizes aggression as either predominately impulsive or premeditated. This study aims to determine the validity and reliability of the IPAS in a sample of Portuguese inmates. A total of 240 inmates were included in the study. A principal component factor analysis was performed so as to obtain the construct validity of the IPAS impulsive aggression (IA) and premeditated aggression (PM) subscales; internal consistency was determined by Cronbach's alpha coefficient; convergent and divergent validity of the subscales were determined analyzing correlations with the Barratt Impulsiveness scale, 11th version (BIS-11), and the Psychopathic Checklist Revised (PCL-R). The rotated matrix with two factors accounted for 49.9% of total variance. IA subscale had 11 items and PM subscale had 10 items. The IA and PM subscales had a good Cronbach's alpha values of 0.89 and 0.88, respectively. The IA subscale is correlated with BIS-11 attentional, motor, and non-planning impulsiveness dimensions (p < 0.05). The PM subscale is correlated with BIS-11 attentional, motor impulsiveness dimensions (p < 0.05). The PM subscale is correlated with PCL-R interpersonal, lifestyle, and antisocial dimensions (p < 0.05). The IA subscale is not correlated with PCL-R. The Portuguese translated version of IPAS has adequate psychometric properties, allowing the measurement of impulsive and premeditated dimensions of aggression

    Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

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    Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

    Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

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    The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

    Challenges of Ageing in Portugal: Data from the EpiDoC Cohort

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    Introduction: Portuguese adults have a long lifespan, but it is unclear whether they live a healthy life in their final years. We aimed to determine the prevalence of multimorbidity and characterize lifestyle and other health outcomes among older Portuguese adults. Material and Methods: We performed a cross-sectional evaluation of 2393 adults, aged 65 and older, during the second wave of follow-up of the EpiDoC cohort, a population-based study involving long-term follow-up of a representative sample of the Portuguese population. Subjects completed a structured questionnaire during a telephone interview. Socioeconomic, demographic, lifestyle behaviours, chronic diseases, and health resources consumption were assessed. Cluster analysis was done to identify dietary patterns. Descriptive and analytic analysis was performed to estimate multimorbidity prevalence and its associated factors. Results: Multimorbidity prevalence among older adults was 78.3%, increased with age strata (72.8% for 65 - 69 years to 83.4% for >= 80 years), and was highest in Azores (84.9%) and Alentejo (83.6%). The most common chronic diseases were hypertension (57.3%), rheumatic disease (51.9%), hypercholesterolemia (49.4%), and diabetes (22.7%). Depression symptoms were frequent (11.8%) and highest in the oldest strata. The mean health-related quality of life (EQ-5D-3L) score was 0.59 +/- 0.38. Hospitalization in the previous 12 months was reported by 25.8% of individuals. Overall, 66.6% of older adults were physically inactive. 'Fruit and vegetables dietary pattern' was followed by 85.4% of individuals; however, regional inequalities were found (69% in Azores). Obesity prevalence was 22.3% overall and was highest among Azoreans (33%). Conclusion: The high prevalence of multimorbidity, combined with unhealthy lifestyle behaviours, suggests that the elderly population constitutes a vulnerable group warranting dedicated intervention
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