Tissue requirements for establishing long-term CD4+ T cell-mediated immunity following Leishmania donovani infection

Organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by Leishmania donovani. Experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. CD4+ T cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. In this study, we show that dendritic cells are critical for CD4+ T cell activation and expansion in all tissue sites examined. We found that FTY720-mediated blockade of T cell trafficking early in infection prevented Ag-specific CD4+ T cells from appearing in lymph nodes, but not the spleen and liver, suggesting that early CD4+ T cell priming does not occur in liver-draining lymph nodes. Extended treatment with FTY720 over the first month of infection increased parasite burdens, although this associated with blockade of lymphocyte egress from secondary lymphoid tissue, as well as with more generalized splenic lymphopenia. Importantly, we demonstrate that CD4+ T cells are required for the establishment and maintenance of antiparasitic immunity in the liver, as well as for immune surveillance and suppression of parasite outgrowth in chronically infected spleens. Finally, although early CD4+ T cell priming appeared to occur most effectively in the spleen, we unexpectedly revealed that protective CD4+ T cell-mediated hepatic immunity could be generated in the complete absence of all secondary lymphoid tissues.

Urinary tract infection of mice to model human disease: Practicalities, implications and limitations

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Murine models of human UTI are vital experimental tools that have helped to elucidate UTI pathogenesis and advance knowledge of potential treatment and infection prevention strategies. Fundamentally, several variables are inherent in different murine models, and understanding the limitations of these variables provides an opportunity to understand how models may be best applied to research aimed at mimicking human disease. In this review, we discuss variables inherent in murine UTI model studies and how these affect model usage, data analysis and data interpretation. We examine recent studies that have elucidated UTI host–pathogen interactions from the perspective of gene expression, and review new studies of biofilm and UTI preventative approaches. We also consider potential standards for variables inherent in murine UTI models and discuss how these might expand the utility of models for mimicking human disease and uncovering new aspects of pathogenesis

Co-distribution and co-infection of chikungunya and dengue viruses

BACKGROUND Chikungunya and dengue infections are spatio-temporally related. The current review aims to determine the geographic limits of chikungunya, dengue and the principal mosquito vectors for both viruses and to synthesise current epidemiological understanding of their co-distribution. METHODS Three biomedical databases (PubMed, Scopus and Web of Science) were searched from their inception until May 2015 for studies that reported concurrent detection of chikungunya and dengue viruses in the same patient. Additionally, data from WHO, CDC and Healthmap alerts were extracted to create up-to-date global distribution maps for both dengue and chikungunya. RESULTS Evidence for chikungunya-dengue co-infection has been found in Angola, Gabon, India, Madagascar, Malaysia, Myanmar, Nigeria, Saint Martin, Singapore, Sri Lanka, Tanzania, Thailand and Yemen; these constitute only 13 out of the 98 countries/territories where both chikungunya and dengue epidemic/endemic transmission have been reported. CONCLUSIONS Understanding the true extent of chikungunya-dengue co-infection is hampered by current diagnosis largely based on their similar symptoms. Heightened awareness of chikungunya among the public and public health practitioners in the advent of the ongoing outbreak in the Americas can be expected to improve diagnostic rigour. Maps generated from the newly compiled lists of the geographic distribution of both pathogens and vectors represent the current geographical limits of chikungunya and dengue, as well as the countries/territories at risk of future incursion by both viruses. These describe regions of co-endemicity in which lab-based diagnosis of suspected cases is of higher priority.

Foil rolling : a new interpretation of experimental results

This paper explores a new interpretation of experiments on foil rolling. The assumption that the roll remains convex is relaxed so that the strip profile may become concave, or thicken in the roll gap. However, we conjecture that the concave profile is associated with phenomena which occur after the rolls have stopped. We argue that the yield criterion must be satisfied in a nonconventional manner if such a phenomenon is caused plastically. Finite element analysis on an extrusion problem appears to confirm this conjecture.

Experimental studies on comparison of microwave curing and thermal curing of epoxy resins used for alternative mould materials

In this present work attempts have been made to study the glass transition temperature of alternative mould materials by using both microwave heating and conventional oven heating. In this present work three epoxy resins, namely R2512, R2515 and R2516, which are commonly used for making injection moulds have been used in combination with two hardeners H2403 and H2409. The magnetron microwave generator used in this research is operating at a frequency of 2.45 GHz with a hollow rectangular waveguide. In order to distinguish the effects between the microwave and conventional heating, a number of experiments were performed to test their mechanical properties such as tensile and flexural strengths. Additionally, differential scanning calorimeter technique was implemented to measure the glass transition temperature on both microwave and conventional heating. This study provided necessary evidences to establish that microwave heated mould materials resulted with higher glass transition temperature than the conventional heating. Finally, attempts were also made to study the microstructure of microwave-cured materials by using a scanning electron microscope in order to analyze the morphology of cured specimens.

Correcting for bias when estimating the cost of hospital-acquired infection : an analysis of lower respiratory tract infections in non-surgical patients

Hospital acquired infections (HAI) are costly but many are avoidable. Evaluating prevention programmes requires data on their costs and benefits. Estimating the actual costs of HAI (a measure of the cost savings due to prevention) is difficult as HAI changes cost by extending patient length of stay, yet, length of stay is a major risk factor for HAI. This endogeneity bias can confound attempts to measure accurately the cost of HAI. We propose a two-stage instrumental variables estimation strategy that explicitly controls for the endogeneity between risk of HAI and length of stay. We find that a 10% reduction in ex ante risk of HAI results in an expected savings of £693 ($US 984).