Editorial: the burden and aetiology of liver cirrhosis, and the risk of death

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122429/1/apt13658_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122429/2/apt13658.pd

Einstein vs Hawking: Black hole binaries and cosmological expansion

This note aims at investigating two different situations where the classical general relativistic dynamics compete with the evolution driven by Hawking evaporation. We focus, in particular, on binary systems of black holes emitting gravitational waves and gravitons, and on the cosmological evolution when black holes are immersed in their own radiation bath. Several non-trivial features are underlined in both cases.Comment: 13 pages, 13 figure

Rapeseed and milk protein exhibit a similar overall nutritional value but marked difference in postprandial regional nitrogen utilization in rats

Background: Rapeseed is an emerging and promising source of dietary protein for human nutrition and health. We previously found that rapeseed protein displayed atypical nutritional properties in humans, characterized by low bioavailability and a high postprandial biological value. The objective of the present study was to investigate the metabolic fate of rapeseed protein isolate (RPI) and its effect on protein fractional synthesis rates (FSR) in various tissues when compared to a milk protein isolate (MPI). Methods: Rats (n = 48) were given a RPI or MPI meal, either for the first time or after 2-week adaptation to a MPI or RPI-based diet. They were divided in two groups for measuring the fed-state tissue FSR 2 h after the meal (using a flooding dose of (13)C-valine) and the dietary N postprandial distribution at 5 h (using (15)N-labeled meals). Results: RPI and MPI led to similar FSR and dietary nitrogen (N) losses (ileal and deamination losses of 4% and 12% of the meal, respectively). By contrast, the dietary N incorporation was significantly higher in the intestinal mucosa and liver (+36% and +16%, respectively) and lower in skin (-24%) after RPI than MPI. Conclusions: Although RPI and MPI led to the same overall level of postprandial dietary N retention in rats (in line with our findings in humans), this global response conceals marked qualitative differences at the tissue level regarding dietary N accretion. The fact that FSR did not however differed between groups suggest a differential modulation of proteolysis after RPI or MPI ingestion, or other mechanisms that warrant further study

Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin

Background: Human gut bacteria can synthesize proteinogenic amino acids and produce a range of metabolites via protein fermentation, some known to exert beneficial or harmful physiological effects on the host. However, the effects of the type and amount of dietary protein consumed on these metabolic processes, as well as the effects of the microbiota-derived amino acids and related metabolites on the host health are still predominantly unknown. Scope and approach:This review provides an up-to-date description of the dominant pathways/genes involved in amino acid metabolism in gut bacteria, and provides an inventory of metabolic intermediates derived from bacterial protein fermentation that may affect human health. Advances in understanding bacterial protein fermentation pathways and metabolites generated at a global level via the implementation of ‘omics’ technologies are reviewed. Finally, the impact of dietary protein intake and high-protein diets on human health is discussed. Key findings and conclusions:The intestinal microbiota is able to synthesize amino acids, but the net result of amino acid production and utilization, according to dietary patterns still needs to be determined. The amount of ingested dietary protein appears to modify both the diversity and composition of the intestinal microbiota as well as the luminal environment of the intestinal epithelium and peripheral tissues. The understanding of the consequences of such changes on the host physiology and pathophysiology is still in an early stage but major progress is expected in the near future with the investigation of host-microbe omics profiles from well-controlled human intervention studies.This works is supported by the European Union's Seventh Framework Program under the grant agreement no 613979 (MyNewGut).Peer reviewe

Liver cirrhosis in England--an observational study: are we measuring its burden occurrence correctly?

Objectives: Mortality due to liver disease (of which cirrhosis is the end‐stage) is increasing more than any other chronic condition in the UK. This study aims to demonstrate that (i) exclusive reliance on mortality rates may not reveal the true burden of liver cirrhosis, and (ii) diverse use of diagnostic coding may produce misleading estimates. Design: Observational study Setting: The Office for National Statistics death registry was interrogated to investigate liver cirrhosis mortality trends in England and Wales, from 1968 to 2011. Main outcome: Standardised mortality trends according to three different definitions of liver cirrhosis based on the specificity of diagnostic codes were calculated: 1(chronic liver diseases), 2 (alcoholic and unspecified cirrhosis only) and 3 (cirrhosis as end‐stage liver disease). The mortality trends were compared to incidence rates established in a previous population‐based study (based on definition 3), from 1998 to 2009, to investigate discrepancies between these two measures. Results: Over the study period, the overall standardised liver cirrhosis mortality rates were 8·8, 5∙1 and 5∙4 per 100,000 person‐years for definitions 1, 2 and 3 of respectively. The mortality rates for definition 3 in 1998 and 2009 were 6∙2 and 5∙9 per 100,000 person‐years respectively; whilst the equivalent incidence rates were at least three‐ and six‐fold higher: 23∙4 and 35∙9 per 100,000 person-years respectively. This discrepancy between incidence and mortality rates was also at least three‐fold in men and women separately, and across age‐groups. Conclusion: Mortality rates underestimated the incidence of liver cirrhosis by at least three‐fold between 1998 and 2009 and varied with differing definitions of disease. Mortality data should not be used exclusively as an indicator for the occurrence of liver cirrhosis in the population. Routinely collected healthcare data are available to measure occurrence of this disease. Careful consideration should be taken when selecting diagnostic codes for cirrhosis

The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Bile duct-ligated mice exhibit multiple phenotypic similarities to acute decompensation patients despite histological differences

DWG is a Wellcome Trust senior research fellow and support for work presented here was provided by the Wellcome Trust

Self-Reported Sleep Duration, Napping, and Incident Heart Failure: Prospective Associations in the British Regional Heart Study.

OBJECTIVES: To examine the associations between self-reported nighttime sleep duration and daytime sleep and incident heart failure (HF) in men with and without preexisting cardiovascular disease (CVD). DESIGN: Population-based prospective study. SETTING: General practices in 24 British towns. PARTICIPANTS: Men aged 60-79 without prevalent HF followed for 9 years (N = 3,723). MEASUREMENTS: Information on incident HF cases was obtained from primary care records. Assessment of sleep was based on self-reported sleep duration at night and daytime napping. RESULTS: Self-reported short nighttime sleep duration and daytime sleep of longer than 1 hour were associated with preexisting CVD, breathlessness, depression, poor health, physical inactivity, and manual social class. In all men, self-reported daytime sleep of longer than 1 hour duration was associated with significantly greater risk of HF after adjustment for potential confounders (adjusted hazard ratio (aHR) = 1.69, 95% CI = 1.06-2.71) than in those who reported no daytime napping. Self-reported nighttime sleep duration was not associated with HF risk except in men with preexisting CVD (<6 hours: aHR = 2.91, 95% CI = 1.31-6.45; 6 hours: aHR = 1.89, 95% CI = 0.89-4.03; 8 hours: aHR = 1.29, 95% CI = 0.61-2.71; ≥9 hours: aHR = 1.80, 905% CI = 0.71-4.61 vs nighttime sleep of 7 hours). Snoring was not associated with HF risk. CONCLUSION: Self-reported daytime napping of longer than 1 hour is associated with greater risk of HF in older men. Self-reported short sleep (<6 hours) in men with CVD is associated with particularly high risk of developing HF