Background/aimsIntestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown.Methods/designWe analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively.ResultsIn ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments.ConclusionsIn ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the ‘leaky’ gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients.

Since a warmer climate is predicted in the future, the incidence of heat wave should increase, and more comprehensive measures, both medical and social, should be adopted to prevent the effects of extreme heat on the population, particularly the elderly.

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During the last few years great attention has been paid to the evaluation of the impact of extreme temperatures on human health. This paper examines the effect of extreme winter temperature on mortality in Madrid for people older than 65, using ARIMA and GAM models. Data correspond to 1,815 winter days over the period 1986-1997, during which time a total of 133,000 deaths occurred. The daily maximum temperature (T(max)) was shown to be the best thermal indicator of the impact of climate on mortality. When total mortality was considered, the maximum impact occurred 7-8 days after a temperature extreme; for circulatory diseases the lag was between 7 and 14 days. When respiratory causes were considered, two mortality peaks were evident at 4-5 and 11 days. When the impact of winter extreme temperatures was compared with that associated with summer extremes, it was found to occur over a longer term, and appeared to be more indirect.

The aim of the present research was to determine the effect of low protein diets on growth performance, carcass traits and ammonia emission from barrows and gilts during the growing and finishing periods. For each period, three diets were formulated. A control diet (C) with 160 and 155 g crude protein (CP)/kg for the growing and finishing, respectively, a medium level diet (M) and a low level diet (L) with 10 and 20 g CP/kg less than the C, respectively. All the diets were supplemented with crystalline amino acids on an ideal protein basis. Barrows (90) and gilts (90) were sorted by bodyweight and sex and housed in three identical manually ventilated chambers. No significant effects of diet on pig performance were observed. In the finishing period, barrows were heavier (P < 0.001) and had higher average daily gain (P < 0.01) and average daily feed intake (P < 0.01) than gilts. Pigs fed the L diet had higher backfat thickness than those fed the other diets in the growing period (P < 0.05). Backfat thickness was higher (P < 0.01) in barrows than in gilts. Muscle depth decreased in pigs fed the L diet in the finishing period. Muscle depth was not affected (P > 0.05) by sex. Average ammonia emissions during the last 6 days were 117.7, 94.2 and 85.5 mg ammonia/kg pig.day for pigs fed the C, M and L diets, respectively. The results show that a reduction in dietary CP of 10 g/kg, accompanied by supplementation with crystalline amino acid reduced ammonia emission by 19.9% with no detrimental effects on growth performance and carcass characteristics, and a reduction of 20 g/kg reduced ammonia emission by 27.3% with no detrimental effects on growth performance but reduced muscle depth at slaughter.