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Endogenous nucleotides produced by various group of cells under inflammatory conditions act as potential danger signals in vivo. Extracellularly released nucleotides such as ATP are rapidly hydrolyzed to adenosine by the coordinated ectonucleotidase activities of CD39 and CD73. Leishmania is an obligate intracellular parasite of macrophages and capable of modulating host immune response in order to survive and multiply within host cells. In this study, the activity of CD73 induced by Leishmania amazonensis in infected macrophages has been investigated and correlated with parasite survival and infection in vitro. For this, the expression of CD39 and CD73, by flow cytometry, in murine peritoneal macrophages infected with metacyclic promastigotes of L. amazonensis has been analyzed. Our results showed that L. amazonensis-infected macrophages, unlike LPS-treated macrophages, increased CD73 expression. It was also noted that when CD73 enzymatic activity was blocked by α, β-methyleneadenosine 5 ′ -diphosphate sodium salt (APCP), macrophage parasitism was significantly decreased. Interestingly, these effects were not associated with the production of TNF-α, IL-10, or nitric oxide (NO). Together, these data demonstrate that L. amazonensis induces a regulatory phenotype in macrophages, which by activating the CD39/CD73 pathway allows parasite survival through the action of immunomodulatory adenosine receptors.

BackgroundThe global elimination of leprosy transmission by 2030 is a World Health Organization (WHO) target. Nepal’s leprosy elimination program depends on early case diagnosis and the performance of health workers and facilities. The knowledge and skills of paramedical staff (Leprosy Focal Person, LFP) and case documentation and management of health facilities is therefore key to the performance of health care services.MethodsThe performance of health workers and facilities was evaluated through a combined cross-sectional and retrospective study approach of 31 health facilities and their LFPs in Dhanusa and Mahottari Districts in Madhesh Province. An average of 6 patients (paucibacillary, PB, or multibacillary, MB) per health facility registered within the 2018/2019 fiscal year were also enrolled in the study. LFP knowledge (e.g., of the three cardinal signs) and skills (e.g., nerve palpation) and facility processes (e.g., record keeping) were scored (e.g., 0, 1) and then rescaled to a proportion, where 1 is perfect. Internal benchmarking was used to guide performance management.ResultsThe overall performance of health care services was 0.43 (95% confidence interval (CI), 0.40-0.46), ranging from 0.33 (95% CI, 0.25-0.40) for LFP knowledge and skills, 0.37 (95% CI, 0.32-0.43) for documentation and 0.60 (95% CI, 0.58-0.61) for case management scores of health facilities. Leprosy-related training was significantly related to the knowledge and skill of the health workers. All identified cases (n =187) adhered to the complete treatment and release after treatment (RFT) scheme, out of which 84.5% were satisfied with the service they were provided. Leprosy disability and Ear Hand and Feet (EHF) scores were not significantly reduced in treated patients, but counseling by LFPs significantly improved cases’ positive belief and practices regarding self-care.ConclusionOverall leprosy care performance was low (43%) and can be improved by evidenced-based training, onsite coaching, monitoring, and supervision to facilitate leprosy transmission elimination. The results highlight many of the challenges facing leprosy elimination programs.

BackgroundNepal has achieved and sustained elimination of leprosy as a public health problem since 2009, but 17 districts and 3 provinces have yet to eliminate the disease. Pediatric cases and grade-2 disabilities (G2D) indicate recent transmission and late diagnosis respectively, which necessitate active and early case detection. This operational research was performed to identify approaches best suited for early case detection, determine community-based leprosy epidemiology, and identify hidden leprosy cases early and respond with prompt treatment.MethodsActive case detection was performed by: house-to-house visits among vulnerable populations (n=26,469), contact examination and tracing (n=7,608) and screening prison populations (n=4,428) in Siraha, Bardiya, Rautahat, Banke, Lalitpur and Kathmandu districts of Nepal.ResultsNew case detection rates were highest for contact tracing (250), followed by house-to-house visits (102) and prison screening (45) per 100,000 population screened. However, cost per case identified was cheapest for house-to-house visits (Nepalese rupee (NPR) 76,500/case), then contact tracing (NPR90,286/case) and prison screening (NPR298,300/case). House-to-house and contact tracing case paucibacillary/multibacillary (PB:MB) ratios were 59:41 and 68:32; female/male ratios 63:37 and 57:43; pediatric cases 11% in both approaches; and G2D 11% and 5% respectively. Developing leprosy was similar among household and neighbor contacts (Odds ratios (OR)=1.4, 95% confidence interval (CI), 0.24-5.85) and for contacts of MB versus PB cases (OR=0.7, 0.26-2.0). Attack rates were similar among household contacts of MB cases (0.32%, 0.07-0.94%) and PB cases (0.13%, 0.03-0.73) and neighbor contacts of MB cases (0.23%, 0.1-0.46) and PB cases (0.48%, 0.19-0.98). BCG vaccination with scar presence had a significant protective effect against leprosy (OR=0.42, 0.22-0.81).ConclusionsThe most effective case identification approach here is contact tracing, followed by house-to-house visits in vulnerable populations and screening in prisons. The findings suggest hidden cases, recent transmission, and late diagnosis in the community exist and highlight the importance of early case detection.

Endogenous nucleotides produced by various group of cells under inflammatory conditions act as potential danger signals

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is currently a threat to malaria elimination due to risk of primaquine-induced haemolysis in G6PD deficient individuals. The World Health Organization (WHO) recommends G6PD screening before providing primaquine as a radical treatment against vivax malaria. However, evidence regarding the prevalence and causing mutations of G6PD deficiency in Nepal is scarce. Methods A cross-sectional, population-based, prevalence study was carried out from May to October 2016 in 12 malaria-endemic districts of Nepal. The screening survey included 4067 participants whose G6PD status was determined by G6PD Care Start™ rapid diagnostic test and genotyping. Results The prevalence of G6PD deficiency at the national level was 3.5% (4.1% among males and 2.1% among females). When analysed according to ethnic groups, G6PD deficiency was highest among the Janajati (6.2% overall, 17.6% in Mahatto, 7.7% in Chaudhary and 7.5% in Tharu) and low among Brahman and Chhetri (1.3%). District-wise, prevalence was highest in Banke (7.6%) and Chitwan (6.6%). Coimbra mutation (592 C>T) was found among 75.5% of the G6PD-deficient samples analysed and Mahidol (487 G>A) and Mediterranean (563 C>T) mutations were found in equal proportions in the remaining 24.5%. There was no specific geographic or ethnic distribution for the three mutations. Conclusions This study has identified populations with moderate to high prevalence of G6PD deficiency which provides strong evidence supporting the WHO recommendations to screen G6PD deficiency at health facility level before the use of primaquine-based radical curative regimen for Plasmodium vivax.

Additional file 1. Tables S1–S5 and Figure S1.

Mammalian cardiac cells are important targets to the protozoan Trypanosoma cruzi. The inflammatory reaction in the host aims at eliminating this parasite, can lead to cell destruction, fibrosis and hypoxia. Local hypoxia is well-defined stimulus to the production of angiogenesis mediators. Assuming that different genetic T. cruzi populations induce distinct inflammation and disease patterns, the current study aims to investigate whether the production of inflammatory and angiogenic mediators is a parasite strain-dependent condition. C57BL/6 mice were infected with the Y and Colombian strains of T. cruzi and euthanized at the 12th and 32nd days, respectively. The blood and heart tissue were processed in immune assays and/or qPCR (TNF, IL-17, IL-10, CCL2, CCL3, CCL5, CCR2, CCR5 and angiogenic factors VEGF, Ang-1, Ang-2) and in histological assays. The T. cruzi increased the inflammatory and angiogenic mediators in the infected mice when they were compared to non-infected animals. However, the Colombian strain has led to higher (i) leukocyte infiltration, (ii) cardiac TNF and CCL5 production/expression, (iii) cardiac tissue parasitism, and to higher (iv) ratio between heart/body weights. On the other hand, the Colombian strain has caused lower production and expression VEGF, Ang-1 and Ang-2, when it was compared to the Y strain of the parasite. The present study highlights that the T. cruzi-genetic population defines the pattern of angiogenic/inflammatory mediators in the heart tissue, and that it may contribute to the magnitude of the cardiac pathogenesis. Besides, such assumption opens windows to the understanding of the angiogenic mediator's role in association with the experimental T. cruzi infection.

Fiber reinforced polymers are widely used in the transportation, aerospace and chemical industries. In rare instances these materials are produced net-shape, and secondary processing such as machining and assembly may be required to produce a finished product. Because fiber reinforced polymers are heterogeneous materials, they do not machine in a similar way to metals. Thus, the theory of metal machining is not valid for the analysis of machining of fiber- reinforced composites. Previous attempts in modeling this problem have adopted Merchant's theory from metal cutting by assuming that chip formation takes place in a shear plane which inclination angle is determined by the minimum energy principle. This class of models showed that model predictions are valid only for fiber orientations less than 60°. The work presented here focuses on providing predictive models for the cutting forces in unidirectional composites. The models are based on the specific cutting energy principle and account for a wide range of fiber orientations and chip thickness. Results from two forms of non-linear modeling methods, non-linear regression and committee neural networks, were compared. It was found that committee neural networks provide better prediction capability by smoothing and capturing the inherent non-linearity in the data. The model predictions were found to be in good agreement with experimental results over the entire range of fiber orientations from 0 to 180°.

Sheet metal parts are widely used in the assembly of aircraft. The most common method of assembling sheet metal parts is through riveting. Failure of a rivet can have severe consequences in terms of loss of human lives and money. There are many parameters associated with a riveting process that directly affect the quality of rivets including squeeze force, rivet length, rivet diameter, and hole diameter tolerance. Incorrect selection or variations in these parameters could induce excessive residual stresses that result in stress concentration sites and initiate cracks, and also result in improper rivet head deformation leading to loose rivets. This paper presents a study of the effect of the aforementioned riveting parameters on the quality of a formed rivet using finite element simulation. The study was part of a larger project carried out for the local aircraft industry and hence, uses the inch system. The research is conducted on a 1/8″ (0.125″) diameter rivet and a 0.064″ thick aluminum sheet. The results indicate that under normal variations in the riveting process parameters, when using the recommended countersunk depth of 0.042″ for rivet hole, most rivets that are formed will not meet the quality requirements. This is primarily due to the existence of a gap between the formed rivet and the hole. Decreasing the countersunk depth to 0.032″ allows for a higher range of hole and rivet diameter tolerances, as well as an increase in the range of squeeze force that can be applied without violating the quality requirements.