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Introduction About one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), leading to 1.4 million deaths and 8.8 million new reported cases of pulmonary tuberculosis (TB) every year [...], Parasitic helminth worms, such as Schistosomamansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.

How healthcare providers distribute their time can impact on the quality and safety of care delivered, and this has been widely studied in hospitals providing care to adult patients. Children are different to adults and the workflow of healthcare providers in paediatric settings is largely unknown. The aim of this study was to quantify how clinical pharmacists working in a paediatric hospital spend their time. A direct observational time and motion study was conducted where two independent observers shadowed seven pharmacists covering eight wards for over 60 hours. Pharmacists spent the majority of time performing medication review (32.6%), followed by communication, non-clinical tasks, supply, medication discussion and in-transit. They were interrupted 3.5 times per hour and spent 4.4% of observed time multi-tasking. This is the first study to quantify how pharmacists in a paediatric hospital distribute their time. These results could act as useful baseline data against which to measure the impact of innovations, such as electronic medication management systems, on pharmacists' workflow. [ABSTRACT FROM AUTHOR]

The contribution of self-peptide-MHC signaling in CD4 + T cells to metabolic programming has not been definitively established. In this study, we employed LLO118 and LLO56, two TCRtg CD4 + T cells that recognize the same Listeria epitope. We previously have shown that LLO56 T cells are highly self-reactive and respond poorly in a primary infection, whereas LLO118 cells, which are less self-reactive, respond well during primary infection. We performed metabolic profiling and found that naive LLO118 had a dramatically higher basal respiration rate, a higher maximal respiration rate, and a higher glycolytic rate relative to LLO56. The LLO118 cells also exhibited a greater uptake of 2-NBD-glucose, in vitro and in vivo. We extended the correlation of low self-reactivity (CD5 lo ) with high basal metabolism using two other CD4 + TCRtg cells with known differences in self-reactivity, AND and Marilyn. We hypothesized that the decreased metabolism resulting from a strong interaction with self was mediated through TCR signaling. We then used an inducible knock-in mouse expressing the Scn5a voltage-gated sodium channel. This channel, when expressed in peripheral T cells, enhanced basal TCR-mediated signaling, resulting in decreased respiration and glycolysis, supporting our hypothesis. Genes and metabolites analysis of LLO118 and LLO56 T cells revealed significant differences in their metabolic pathways, including the glycerol phosphate shuttle. Inhibition of this pathway reverts the metabolic state of the LLO118 cells to be more LLO56 like. Overall, these studies highlight the critical relationship between peripheral TCR-self-pMHC interaction, metabolism, and the immune response to infection., (Copyright © 2020 The Authors.)