Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Testing and comparing two self-care-related instruments among older Chinese adults

Objectives The study aimed to test and compare the reliability and validity, including sensitivity and specificity of the two self-care-related instruments, the Self-care Ability Scale for the Elderly (SASE), and the Appraisal of Self-care Agency Scale-Revised (ASAS-R), among older adults in the Chinese context. Methods A cross-sectional design was used to conduct this study. The sample consisted of 1152 older adults. Data were collected by a questionnaire including the Chinese version of SASE (SASE-CHI), the Chinese version of ASAS-R (ASAS-R-CHI) and the Exercise of Self-Care Agency scale (ESCA). Homogeneity and stability, content, construct and concurrent validity, and sensitivity and specificity were assessed. Results The Cronbach's alpha (α) of SASE-CHI was 0.89, the item-to-total correlations ranged from r = 0.15 to r = 0.81, and the test-retest correlation coefficient (intra-class correlation coefficient, ICC) was 0.99 (95% CI, 0.99±1.00; P<0.001). The Cronbach's α of ASAS-R-CHI was 0.78, the item-to-total correlations ranged from r = 0.20 to r = 0.65, and the test-retest ICC was 0.95 (95% CI, 0.92±0.96; P<0.001). The content validity index (CVI) of SASE-CHI and ASAS-R-CHI was 0.96 and 0.97, respectively. The findings of exploratory and confirmatory factor analyses (EFA and CFA) confirmed a good construct validity of SASE-CHI and ASAS-R-CHI. The Pearson's rank correlation coefficients, as a measure of concurrent validity, between total score of SASE-CHI and ESCA and ASAS-R-CHI and ESCA were assessed to 0.65 (P<0.001) and 0.62 (P<0.001), respectively. Regarding ESCA as the criterion, the area under the receiver operator characteristic (ROC) curve for the cut-point of SASE-CHI and ASAS-R-CHI were 0.93 (95% CI, 0.91±0.94) and 0.83 (95% CI, 0.80±0.86), respectively. Conclusion There is no significant difference between the two instruments. Each has its own characteristics, but SASE-CHI is more suitable for older adults. The key point is that the users can choose the most appropriate scale according to the specific situation.publishedVersionNivå

Pan-Atlantic analysis of the overlap of a highly migratory species, the leatherback turtle, with pelagic longline fisheries

This is the final version of the article. Available from the publisher via the DOI in this record.Large oceanic migrants play important roles in ecosystems, yet many species are of conservation concern as a result of anthropogenic threats, of which incidental capture by fisheries is frequently identified. The last large populations of the leatherback turtle, Dermochelys coriacea, occur in the Atlantic Ocean, but interactions with industrial fisheries could jeopardize recent positive population trends, making bycatch mitigation a priority. Here, we perform the first pan-Atlantic analysis of spatio-temporal distribution of the leatherback turtle and ascertain overlap with longline fishing effort. Data suggest that the Atlantic probably consists of two regional management units: northern and southern (the latter including turtles breeding in South Africa). Although turtles and fisheries show highly diverse distributions, we highlight nine areas of high susceptibility to potential bycatch (four in the northern Atlantic and five in the southern/equatorial Atlantic) that are worthy of further targeted investigation and mitigation. These are reinforced by reports of leatherback bycatch at eight of these sites. International collaborative efforts are needed, especially from nations hosting regions where susceptibility to bycatch is likely to be high within their exclusive economic zone (northern Atlantic: Cape Verde, Gambia, Guinea Bissau, Mauritania, Senegal, Spain, USA and Western Sahara; southern Atlantic: Angola, Brazil, Namibia and UK) and from nations fishing in these high-susceptibility areas, including those located in international waters.Work in Gabon was financially supported by the Large Pelagics Research Center through National Oceanographic and Atmospheric Agency award no. NA04NMF4550391, the UK Defra Darwin Initiative, the Shellshock Campaign (European Association for Zoos and Aquaria) and the UK Natural Environment Research Council. Sea turtle monitoring programmes in Gabon were financially supported by the Wildlife Conservation Society and by the Gabon Sea Turtle Partnership with funding from the Marine Turtle Conservation Fund (United States Fish and Wildlife Service, US Department of the Interior). Four of the satellite tags were deployed in Canadian waters by M. James (Dalhousie University) and the Canadian Sea Turtle Network, with the funding support of Canadian Sea Turtle Network leatherback field research provided by R. A. Myers, the Canadian Wildlife Federation, Environment Canada and WWF-Canada. Work in French Guiana was financially supported by CNES, DEAL and the European Union.This study results from the collaborative effort of 10 data providers, which have satellite-tracked leatherback turtles in the Atlantic Ocean since 1995, through their voluntary participation in the Trans-Atlantic Leatherback Conservation Initiative (TALCIN), a WWF-led initiative. We thank C. Drews (WWF-International) and Jean-Yves Georges (IPHC-CNRS) for having initiated this project. Significant contributions were made by A. Fonseca and M. L. Felix and the WWF Guianas office in fostering this project to secure its continuation. We thank those involved in the sea turtle restoration plan in French Guiana (DEAL, ONCFS, Kulalasi NGO, Kwata, the Reserve Naturelle de l'Amana, Chiefs of Awala and Yalimapo), Yvon Le Maho (IPHC-CNRS) for having initiated the leatherback tracking programme in French Guiana, colleagues from the Regional Program for Sea Turtles Research and Conservation of Argentina–PRICTMA, Aquamarina and Fundación Mundo Marino, the onboard scientific observers from PNOFA-DINARA, the crew and owner of the F/V Torres del Paine, the artisanal fishermen from Kiyú, San José, Uruguay, D. del Bene (PROFAUMA), Z. Di Rienzo and colleagues from Karumbé, the University of Pisa for initiating the satellite tagging programmes in South Africa, and the South African Department of Environmental Affairs for continuing the work in cooperation with Dr Nel from the Nelson Mandela Metropolitan University, Port Elizabeth and Ezemvelo KZN Wildlife. We thank M. L. Felix for her efforts in the deployment of satellite tags in Suriname and the Nature Conservation Division Suriname for facilitating these research efforts. P.M. thanks C. Palma for his help in dealing with ICCAT's database, C. Ere, as well as the GIS training and support received from SCGIS and the ESRI Conservation Program, which allowed processing of fishing-effort data. We thank J. Parezo for her careful reading of the manuscript. All authors designed the study and contributed data; S.F, M.S.C., P.M. and M.J.W. compiled the data; S.F., M.A.N. and A.L. coordinated and supervised the project; S.F., M.J.W., P.M. and B.J.G. led the data analysis and interpretation with contributions from all authors; the manuscript was developed by S.F. and M.J.W. as lead authors, with contributions from all authors

Smoking in preeclamptic women is associated with higher birthweight for gestational age and lower soluble fms-like tyrosine kinase-1 levels: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers.</p> <p>Methods</p> <p>From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit.</p> <p>Results</p> <p>In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054).</p> <p>Conclusions</p> <p>Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1.</p

Jogo educativo sobre drogas para cegos: construção e avaliação

Estudo realizado com o objetivo de construir e avaliar um jogo educativo sobre drogas psicoativas acessível a pessoas cegas, desenvolvido em três etapas: construção do jogo educativo, avaliação por três especialistas em educação especial e doze cegos. Foi construído um jogo de tabuleiro denominado Drogas: jogando limpo . Na Versão Alfa os especialistas fizeram sugestões em relação às e instruções e ao tabuleiro: textura das casas, peças do jogo e escrita em Braille. Na Versão Beta, procedeu-se à avaliação pelos cegos, os quais sugeriram alterações na textura das casas e colocação de velcro para fixação do pino no tabuleiro. Passou-se, então, à Versão Gama, jogada pelas últimas três duplas de cegos e considerada adequada. Na avaliação dos juízes, o jogo revelou-se adequado, pois permite o acesso à informação sobre drogas psicoativas de maneira lúdica

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Probing natural SUSY from stop pair production at the LHC

We consider the natural supersymmetry scenario in the framework of the R-parity conserving minimal supersymmetric standard model (called natural MSSM) and examine the observability of stop pair production at the LHC. We first scan the parameters of this scenario under various experimental constraints, including the SM-like Higgs boson mass, the indirect limits from precision electroweak data and B-decays. Then in the allowed parameter space we study the stop pair production at the LHC followed by the stop decay into a top quark plus a lightest neutralino or into a bottom quark plus a chargino. From detailed Monte Carlo simulations of the signals and backgrounds, we find the two decay modes are complementary to each other in probing the stop pair production, and the LHC with $\sqrt{s}= 14$ TeV and 100 $fb^{-1}$ luminosity is capable of discovering the stop predicted in natural MSSM up to 450 GeV. If no excess events were observed at the LHC, the 95% C.L. exclusion limits of the stop masses can reach around 537 GeV.Comment: 19 pages, 10 figures, version accepted by JHE