Transcriptional memory-like imprints and enhanced functional activity in gamma delta T cells following resolution of malaria infection

Gamma delta T cells play an essential role in the immune response to many pathogens, including Plasmodium. However, long-lasting effects of infection on the gamma delta T cell population still remain inadequately understood. This study focused on assessing molecular and functional changes that persist in the gamma delta T cell population following resolution of malaria infection. We investigated transcriptional changes and memory-like functional capacity of malaria pre-exposed gamma delta T cells using a Plasmodium chabaudi infection model. We show that multiple genes associated with effector function (chemokines, cytokines and cytotoxicity) and antigen-presentation were upregulated in P. chabaudi-exposed gamma delta T cells compared to gamma delta T cells from naive mice. This transcriptional profile was positively correlated with profiles observed in conventional memory CD8(+) T cells and was accompanied by enhanced reactivation upon secondary encounter with Plasmodium-infected red blood cells in vitro. Collectively our data demonstrate that Plasmodium exposure result in "memory-like imprints" in the gamma delta T cell population and also promotes gamma delta T cells that can support antigen-presentation during subsequent infections

De novo HNF4A-associated atypical Fanconi renal tubulopathy syndrome

Nephrolog

Randomised controlled trial of GP-led in-hospital management of homeless people ('Pathway')

The study was funded by the National Institute for Health Researc

Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study

Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design: RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Results: Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5–7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion: Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required

Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007

Simon Hay and colleagues derive contemporary estimates of the global clinical burden of Plasmodium falciparum malaria (the deadliest form of malaria) using cartography-based techniques

Research Methodologies and Business Discourse Teaching

This chapter will:; ; ; Define English for specific purposes and indicate the specific ways in which it has been influential on business discourse teaching;; ; ; Discuss the most relevant approaches to genre analysis that have been used in business discourse teaching;; ; ; Explore the most relevant approaches to critical discourse analysis and organizational rhetoric for business discourse teaching;; ; ; Identify the most relevant aspects of multimodal discourse analysis for business discourse teaching;; ; ; Provide a case study that illustrates the use of one approach to business discourse teaching, showing how practitioners can incorporate it into their classroom- or consultancy-based ideas