Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.     

Experimental evidence that ground‐disturbance benefits Woodlark Lullula arborea

To determine whether ground‐disturbance increased Woodlark Lullula arborea abundance, we examined responses over 3 years to four treatments varying in establishment method (shallow‐ or deep‐cultivated) and complexity (homogeneous or ‘complex‐mosaics’ comprising fallow and recently cultivated subplots), plus controls, replicated across the largest lowland grass‐heath in the UK. Abundance increased through the study and was higher on plots closer to woodland and across all treatments. Within complex‐mosaics, Woodlark preferentially used recently cultivated subplots over 1‐ or 2‐year‐old fallows. Regardless of treatment detail, providing suitable foraging habitat within c. 45 m of woodland, through annual ground‐disturbance, can increase Woodlark abundance within lowland grass‐heaths characterized by closed swards.     

Comparative phylogeographic summary statistics for testing simultaneous vicariance

Testing for simultaneous vicariance across comparative phylogeographic data sets is a notoriously difficult problem hindered by mutational variance, the coalescent variance, and variability across pairs of sister taxa in parameters that affect genetic divergence. We simulate vicariance to characterize the behaviour of several commonly used summary statistics across a range of divergence times, and to characterize this behaviour in comparative phylogeographic datasets having multiple taxon-pairs. We found Tajima's D to be relatively uncorrelated with other summary statistics across divergence times, and using simple hypothesis testing of simultaneous vicariance given variable population sizes, we counter-intuitively found that the variance across taxon pairs in Nei and Li's net nucleotide divergence (pi(net)), a common measure of population divergence, is often inferior to using the variance in Tajima's D across taxon pairs as a test statistic to distinguish ancient simultaneous vicariance from variable vicariance histories. The opposite and more intuitive pattern is found for testing more recent simultaneous vicariance, and overall we found that depending on the timing of vicariance, one of these two test statistics can achieve high statistical power for rejecting simultaneous vicariance, given a reasonable number of intron loci (> 5 loci, 400 bp) and a range of conditions. These results suggest that components of these two composite summary statistics should be used in future simulation-based methods which can simultaneously use a pool of summary statistics to test comparative the phylogeographic hypotheses we consider here.     

Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice

These preclinical studies aimed to 1) increase our understanding the dietary induction of nonalcoholic steatohepatitis (NASH), and, 2) further explore the utility and mechanisms of glucagon-like peptide-1 receptor (GLP-1R) agonism in NASH. We compared the effects of a high trans-fat (HTF) or high lard fat (HLF) diet on key facets of nonalcoholic fatty liver disease (NAFLD)/NASH in Lep(ob)/Lep(ob) and C57BL6J (B6) mice. Although HLF-fed mice experienced overall greater gains in weight and adiposity, the addition of trans-fat better mirrored pathophysiological features of NASH (e.g., hepatomegaly, hepatic lipid, and fibrosis). Administration of AC3174, an exenatide analog, and GLP-1R agonist to Lep(ob)/Lep(ob) and B6 ameliorated hepatic endpoints in both dietary models. Next, we assessed whether AC3174-mediated improvements in diet-induced NASH were solely due to weight loss in HTF-fed mice. AC3174-treatment significantly reduced body weight (8.3%), liver mass (14.2%), liver lipid (12.9%), plasma alanine aminotransferase, and triglycerides, whereas a calorie-restricted, weight-matched group demonstrated only modest nonsignificant reductions in liver mass (9%) and liver lipid (5.1%) relative to controls. Treatment of GLP-1R-deficient (GLP-1RKO) mice with AC3174 had no effect on body weight, adiposity, liver or plasma indices pointing to the GLP-1R-dependence of AC3174's effects. Interestingly, the role of endogenous GLP-1Rs in NASH merits further exploration as the GLP-1RKO model was protected from the deleterious hepatic effects of HTF. Our pharmacological data further support the clinical evaluation of the utility of GLP-1R agonists for treatment of NASH.     

Melatonin suppresses AOM/DSS-induced large bowel oncogenesis in rats

The inhibitory effects of exogenous melatonin (MEL) on colon oncogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) rat model. Male F344 rats initiated with a single intraperitoneal injection of AOM (20 mg/kg bw) were promoted by 1% (w/v) DSS in drinking water for 7 days. They were then given 0.4, 2 or 10 ppm MEL in drinking water for 17 weeks. At week 20, the development of colonic adenocarcinoma was significantly inhibited by the administration with MEL dose-dependently. MEL exposure modulated the mitotic and apoptotic indices in the colonic adenocarcinomas that developed and lowered the immunohistochemical expression of nuclear factor kappa B, tumor necrosis factor α, interleukin-1β and STAT3 in the epithelial malignancies. These results may indicate the beneficial effects of MEL on colitis-related colon carcinogenesis and a potential application for inhibiting colorectal cancer development in the inflamed colon.     

Combined mitochondrial and nuclear data enhance resolution of a rapid radiation of Australian rainbow skinks (Scincidae: Carlia)

In contrast to low diversity seen in many Australian rainforest squamate genera, sclerophyll adapted groups—such as Carlia—show signs of faster diversification. Here we expand upon a previous single-locus mitochondrial DNA phylogenetic study of Carlia which described a major polytomy at an intermediate level of divergence. With additional mtDNA data, two nuclear intron loci and comprehensive taxonomic coverage, we provide support, congruent across loci, for the existence of three major clades. In doing so we recognise three genera for the ‘Carlia group of skinks’: clade 1, Carlia Gray, 1845; 2, Lygisaurus De Vis, 1884 (includes all species formerly known as Lygisaurus, and also includes C. parrhasius); 3, Liburnascincus Wells and Wellington, 1984 (consisting of three boulder-dwelling species). Remaining regions of low bootstrap and posterior probability support are associated with short internodes and apparent conflict among loci, as inferred by Partition Branch Support. Likelihood-based diversification-rate analysis rejects constant rate models, and indicates that Carlia underwent a period of relatively rapid diversification early in the evolution of the group, a rate 3–4 times faster than subsequent rates, and faster than comparable wet forest skinks.     

Characterisation of microsatellite loci in the subtidal habitat-forming alga, Phyllospora comosa (Phaeophyceae, Fucales)

Habitat-forming macroalgae play a central role in the ecology of temperate reefs worldwide but there exists a critical lack of knowledge about important processes such as dispersal and gene flow. Understanding dispersal and gene flow of habitat-forming seaweeds is particularly pertinent given that loss of habitat-forming algae is an increasingly prevalent problem worldwide. Here, we develop 10 microsatellite markers for the monotypic Phyllospora comosa, an important habitat-forming macroalga that has undergone massive declines on urbanised coastlines of Sydney, Australia. We characterise population genetic diversity and structure and estimate levels of dispersal and gene flow between the geographically isolated northern and southern populations in this subtidal macroalga.     

Non-uniform distribution of mitochondria in pancreatic acinar cells

The distribution of mitochondria in pancreatic acinar cells was investigated using confocal fluorescence microscopy and transmission electron microscopy (EM). Acinar cells were studied either after enzymatic isolation or in small segments of undisassociated pancreatic tissue. Loading of isolated acinar cells with Mito Tracker Green or Red, a fluorescence mitochondrial probe, showed that mitochondria are predominantly situated in the perigranular, subplasmalemmal and perinuclear regions. Subsequent applications of EM fixatives induced a leak of the fluorescent indicator to the cytosol but did not change the distribution of mitochondria. EM was then performed on isolated acinar cells and on acinar cells of pancreatic tissue segments. The intracellular distribution of mitochondria was quantified by calculating the percentage of the cross-sectional area that was occupied by mitochondria. In isolated acinar cells the highest density of mitochondria was seen in the perigranular region, where mitochondria occupied 25.69±1.58% of the area, then the subplasmalemmal region with 12.61±0.77% and the perinuclear region with 9.07±0.97% (n=26). Similar results were obtained from acinar cells of pancreatic tissue segments: the perigranular 22.9±1.95%, subplasmalemmal 12.45±0.78% and perinuclear regions 9.07±0.97% (n=26). The outer mitochondrial membranes were frequently positioned close to membranes of the ER, which followed the outer contour of mitochondria. Mitochondria were never found in direct contact with the nuclear envelope: there were usually layers of ER between the mitochondrial and nuclear membranes. Subplasmalemmal mitochondria were found in a very close proximity to the plasma membrane with no ER layers between the mitochondrial and the corresponding plasma membranes. We conclude that in pancreatic acinar cells mitochondria are preferentially distributed to perigranular, subplasmalemmal and perinuclear regions and this distribution is not affected by isolation or fixation procedures.P.R. Johnson and N.J. Dolman contributed equally to the study. This work was supported by a Medical Research Council programme grant. P.R.J. is a Medical Research Council PhD student and N.J.D. is a Wellcome Trust PhD student.