The impact of pathogen burden on leukocyte telomere length in the Multi-Ethnic Study of Atherosclerosis

Several infections have been linked to telomere shortening and in some cases these associations have varied by sex. We assessed the association between seropositivity to four persistent pathogens (cytomegalovirus (CMV), herpes simplex virus-1, Helicobacter pylori, Chlamydia pneumoniae), and total pathogen burden on leukocyte telomere length in a diverse US sample. Data came from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study. We utilized cross-sectional survey data, and biological samples from participants tested for pathogens and telomere length (N = 163). Linear regression was used to examine the association between seropositivity for individual pathogens as well as total pathogen burden and telomere length, adjusting for various confounders. CMV seropositivity and increased total pathogen burden level were significantly associated with shorter telomere length among females (β = -0·1204 (standard error (s.e.) 0·06), P = 0·044) and (β = -0·1057 (s.e. = 0·05), P = 0·033), respectively. There was no statistically significant association among males. Our findings suggest that prevention or treatment of persistent pathogens, in particular CMV, may play an important role in reducing telomere shortening over the life course among women. Future research is needed to confirm these novel findings in larger longitudinal samples

A lattice model for the kinetics of rupture of fluid bilayer membranes

We have constructed a model for the kinetics of rupture of membranes under tension, applying physical principles relevant to lipid bilayers held together by hydrophobic interactions. The membrane is characterized by the bulk compressibility (for expansion), the thickness of the hydrophobic part of the bilayer, the hydrophobicity and a parameter characterizing the tail rigidity of the lipids. The model is a lattice model which incorporates strain relaxation, and considers the nucleation of pores at constant area, constant temperature, and constant particle number. The particle number is conserved by allowing multiple occupancy of the sites. An equilibrium ``phase diagram'' is constructed as a function of temperature and strain with the total pore surface and distribution as the order parameters. A first order rupture line is found with increasing tension, and a continuous increase in proto-pore concentration with rising temperature till instability. The model explains current results on saturated and unsaturated PC lipid bilayers and thicker artificial bilayers made of diblock copolymers. Pore size distributions are presented for various values of area expansion and temperature, and the fractal dimension of the pore edge is evaluated.Comment: 15 pages, 8 figure

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Mitochondrial DNA mutations in human colonic crypt stem cells

The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell