Ureaplasma species multiple banded antigen (MBA) variation is associated with the severity of chorioamnionitis in late preterm placentas

Background: Intra-amniotic infection accounts for 30% of all preterm births (PTB), with the human Ureaplasma species being the most frequently identified microorganism from the placentas of women who deliver preterm. The highest prevalence of PTB occurs late preterm (32-36 weeks) but no studies have investigated the role of infectious aetiologies associated with late preterm birth. Method: Placentas from women with late PTB were dissected aseptically and samples of chorioamnion tissue and membrane swabs were collected. These were tested for Ureaplasma spp. and aerobic/anaerobic bacteria by culture and real-time PCR. Western blot was used to assess MBA variation in ureaplasma clinical isolates. The presence of microorganisms was correlated with histological chorioamnionitis. Results: Ureaplasma spp. were isolated from 33/466 (7%) of placentas by culture or PCR. The presence of ureaplasmas, but not other microorganisms, was associated with histological chorioamnionitis (21/33 ureaplasma-positive vs. 8/42 other bacteria; p= 0.001). Ureaplasma clinical isolates demonstrating no MBA variation were associated with histological chorioamnionitis. By contrast, ureaplasmas displaying MBA variation were isolated from placentas with no significant histological chorioamnionitis (p= 0.001). Conclusion: Ureaplasma spp. within placentas delivered late preterm (7%) is associated with histological chorioamnionitis (p = 0.001). Decreased inflammation within chorioamnion was observed when the clinical ureaplasma isolates demonstrated variation of their surface-exposed lipoproteins (MBA). This variation may be a mechanism by which ureaplasmas modulate and evade the host immune response. So whilst ureaplasmas are present intra-amniotically they are not suspected because of the normal macroscopic appearance of the placentas and the amniotic fluid.

Principal component and linkage analysis of cardiovascular risk traits in the Norfolk isolate

OBJECTIVE(S): An individual's risk of developing cardiovascular disease (CVD) is influenced by genetic factors. This study focussed on mapping genetic loci for CVD-risk traits in a unique population isolate derived from Norfolk Island. METHODS: This investigation focussed on 377 individuals descended from the population founders. Principal component analysis was used to extract orthogonal components from 11 cardiovascular risk traits. Multipoint variance component methods were used to assess genome-wide linkage using SOLAR to the derived factors. A total of 285 of the 377 related individuals were informative for linkage analysis. RESULTS: A total of 4 principal components accounting for 83% of the total variance were derived. Principal component 1 was loaded with body size indicators; principal component 2 with body size, cholesterol and triglyceride levels; principal component 3 with the blood pressures; and principal component 4 with LDL-cholesterol and total cholesterol levels. Suggestive evidence of linkage for principal component 2 (h(2) = 0.35) was observed on chromosome 5q35 (LOD = 1.85; p = 0.0008). While peak regions on chromosome 10p11.2 (LOD = 1.27; p = 0.005) and 12q13 (LOD = 1.63; p = 0.003) were observed to segregate with principal components 1 (h(2) = 0.33) and 4 (h(2) = 0.42), respectively. CONCLUSION(S): This study investigated a number of CVD risk traits in a unique isolated population. Findings support the clustering of CVD risk traits and provide interesting evidence of a region on chromosome 5q35 segregating with weight, waist circumference, HDL-c and total triglyceride levels.

Changes in health profiles of participants in an Australian police department’s Wellness program

Background: Little is known about the health effects of worksite wellness programs on police department staff. Objective: To examine 1-2 year changes in health profiles of participants in the Queensland Police Service’s wellness program. Methods: Participants underwent yearly physical assessments. Health profile data collected during assessments from 2008 to 2012 were included in the analysis. Data Analysis: Repeated-measures ANOVA was used for continuous outcome variables, related-samples Wilcoxon Signed Rank test for non-normally continuous variables, and McNemar’s test for binary variables. Results: Significant changes in physical measures included decreases in waist circumference and percent body fat, and increases in cardiorespiratory fitness and flexibility (p<0.01). Changes in serum cholesterol, haemoglobin, total cholesterol ratios, HDL, LDL and Triglyceride levels were also significant (p<0.01). Conclusion: Participants’ health profiles mostly improved between cycles although most changes were not clinically significant. As this evaluation used a single-group pre-test post-test design, it provides initial indications that wellness programs can benefit staff in police departments.

Cross-sectional study of a microsatellite marker in the low densitity lipoprotein receptor gene in obese normotensives

1. The low density lipoprotein receptor is an important regulator of serum cholesterol which may have implications for the development of both hypertension and obesity. In this study, genotypes for a low density lipoprotein receptor gene (LDLR) dinucleotide polymorphism were determined in both lean and obese normotensive populations. 2. In previous cross-sectional association studies an ApaLI and a HincII polymorphism for LDLR were shown to be associated with obesity in essential hypertensives. However, these polymorphisms did not show an association with obesity in normotensives. 3. In contrast, this study reports that preliminary results for an LDLR microsatellite marker, located more towards the 3' end of the gene, show a significant association with obesity in the normotensive population studied. These results indicate that LDLR could play an important role in the development of obesity, which might be independent of hypertension.

Association of a low density lipoprotein receptor microsatellite variant with obesity

OBJECTIVE To determine whether a microsatellite polymorphism located towards the 3' end of the low density lipoprotein receptor gene (LDLR) is associated with obesity. DESIGN A cross-sectional case-control study. SUBJECTS One hundred and seven obese individuals, defined as a body mass index (BMI) ≤ 26 kg/m2, and 163 lean individuals, defined as a BMI < 26 kg/m2. MEASUREMENTS BMI, blood pressure, serum lipids, alleles of LDLR microsatellite (106 bp, 108 bp and 112 bp). RESULTS There was a significant association between variants of the LDLR microsatellite and obesity, in the overall tested population, due to a contributing effect in females (χ2 = 12.3, P = 0.002), but not in males (χ2 = 0.3, P = 0.87). In females, individuals with the 106 bp allele were more likely to be lean, while individuals with the 112 bp and/or 108 bp alleles tended to be obese. CONCLUSIONS These results suggest that in females, LDLR may play a role in the development of obesity.

Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives

Obese (BMI ≥ 26 kg/m 2; n = 51) and lean (BMI <26 kg/m 2; n = 61) Caucasian patients with severe, familial essential hypertension, were compared with respect to genotype and allele frequencies of a HincII RFLP of the low density lipoprotein receptor gene (LDLR). A similar analysis was performed in obese (n = 28) and lean (n = 68) normotensives. A significant association of the C allele of the T→C variant responsible for this RFLP was seen with obesity (χ 2 = 4.6, P = 0.029) in the hypertensive, but not in the normotensive, group (odds ratio = 3.0 for the CC genotype and 2.7 for CT). Furthermore, BMI tracked with genotypes of this allele in the hypertensives (P = 0.046). No significant genotypic relationship was apparent for plasma lipids. Significant linkage disequilibrium was, moreover, noted between the HincII RFLP and an ApaLI RFLP (χ 2 = 33, P<0.0005) that has previously shown even stronger association with obesity (odds ratio 19.6 for cases homozygous for the susceptibility allele and 15.2 for het-erozygotes). The present study therefore adds to our previous evidence implicating LDLR as a locus for obesity in patients with essential hypertension.

Corticosterone accelerates atherosclerosis in the apolipoprotein E-deficient mouse

Chronic stress is an important risk factor for atherosclerosis, which is a chief process in the development of cardiovascular disease. Increased circulating levels of corticosterone have been documented in several animal models of chronic stress. However, it remains to be established whether corticosterone is sufficient to exacerbate atherosclerosis. To test this hypothesis, apolipoprotein E (ApoE)-deficient mice were fed a high-fat diet for 13 weeks with exposure to either corticosterone or vehicle in the drinking water (CORT and Con). Corticosterone treatment significantly increased atherosclerotic plaque area at the aortic root. Such exacerbation of atherosclerosis was accompanied by significantly lower levels of circulating white blood cells and serum interleukin-1β (IL-1β), and significantly elevated serum concentrations of total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and small dense low-density lipoprotein (sd-LDL) in CORT mice when compared to Con mice. These findings demonstrate that corticosterone is sufficient to exacerbate atherosclerosis in vivo despite its anti-inflammatory properties and that this marked pro-atherogenic phenotype is primarily associated with increased dyslipidaemia.

Effect of a single session of exercise on lipoprotein(a)

Lipoprotein(a) (Lp(a)) is bound to apolipoprotein B-100 by disulfide linkage and is associated in the upper density range of low density lipoprotein cholesterol. Persons with elevated concentrations of Lp(a) are regarded as having an increased risk for premature coronary artery disease. Although many studies exist evaluating the effects of a single session of exercise on lipids and lipoproteins, little information is available concerning the effects of exercise on Lp(a). Therefore, the purpose of this study was to determine the effects of a single exercise session on plasma Lp(a). Twelve physically active men completed two 30-min submaximal treadmill exercise sessions: low intensity (LI, 50% VO2max) and high intensity (HI, 80% VO2max). Blood samples were obtained immediately before and after exercise. Total cholesterol (LI: before 4.22 +/- 0.26, after 4.24 +/- 0.28; HI: before 4.24 +/- 0.31, after 4.11 +/- 0.28 mmol . l(-1), mean +/- SE) and triglyceride (LI: before 1.14 +/- 0.16, after 1.06 +/- 0.16; HI: before 1.12 +/- 0.19, after 1.21 +/- 0.19 mmol . l(-1)) concentrations did not differ immediately after either exercise session, nor did Lp(a) concentrations differ immediately after either exercise session (LI: before 4.1 +/- 2.2, after 4.0 +/- 2.1; HI: before 3.9 +/- 2.2, after 3.7 +/- 2.0 mg . dl(-1)). These results suggest that neither a low nor a high intensity exercise session lasting 30 min in duration has an immediate effect on plasma Lp(a).

Going live : building academic capacity in blended learning using web-conferencing technologies

This paper reports on a current initiative at Queensland University of Technology to provide timely, flexible and sustainable training and support to academic staff in blended learning and associated techno-pedagogies via a web-conferencing classroom and collaboration tool, Elluminate Live!. This technology was first introduced to QUT in 2008 as part of the university‘s ongoing commitment to meeting the learning needs of diverse student cohorts. The centralised Learning Design team, in collaboration with the university‘s department of eLearning Services, was given the task of providing training and support to academic staff in the effective use of the technology for teaching and learning, as part of the team‘s ongoing brief to support and enhance the provision of blended learning throughout the university. The resulting program, ―Learning Design Live‖ (LDL) is informed by Rogers‘ theory of innovation and diffusion (2003) and structured according to Wilson‘s framework for faculty development (2007). This paper discusses the program‘s design and structure, considers the program‘s impact on academic capacity in blended learning within the institution, and reflects on future directions for the program and emerging insights into blended learning and participant engagement for both staff and students.

Instant coffee with high chlorogenic acid levels protects humans against oxidative damage of macromolecules

Scope: Coffee is among the most frequently consumed beverages. Its consumption is inversely associated to the incidence of diseases related to reactive oxygen species; the phenomenon may be due to its antioxidant properties. Our primary objective was to investigate the impact of consumption of a coffee containing high levels of chlorogenic acids on the oxidation of proteins, DNA and membrane lipids; additionally, other redox biomarkers were monitored in an intervention trial. Methods and results: The treatment group (n=36) consumed instant coffee co-extracted from green and roasted beans, whereas the control consumed water (800 mL/P/day, 5 days). A global statistical analysis of four main biomarkers selected as primary outcomes showed that the overall changes are significant. 8-Isoprostaglandin F2α in urine declined by 15.3%, 3-nitrotyrosine was decreased by 16.1%, DNA migration due to oxidized purines and pyrimidines was (not significantly) reduced in lymphocytes by 12.5 and 14.1%. Other markers such as the total antioxidant capacity were moderately increased; e.g. LDL and malondialdehyde were shifted towards a non-significant reduction. Conclusion: The oxidation of DNA, lipids and proteins associated with the incidence of various diseases and the protection against their oxidative damage may be indicative for beneficial health effects of coffee.

No indications of persistent oxidative stress in response to an ironman triathlon

Introduction: Training for and competing in ultraendurance exercise events is associated with an improvement in endogenous antioxidant defenses as well as increased oxidative stress. However, consequences on health are currently unclear. Purpose: We aimed to examine the impact of training- and acute exercise-induced changes in the antioxidant capacity on the oxidant/antioxidant balance after an ironman triathlon and whether there are indications for sustained oxidative damage. Methods: Blood samples were taken from 42 well-trained male triathletes 2 d before an ironman triathlon, then immediately postrace, 1, 5, and 19 d later. Blood was analyzed for conjugated dienes (CD), malondialdehyde (MDA), oxidized low-density lipoprotein (oxLDL), oxLDL:LDL ratio, advanced oxidation protein products (AOPP), AOPP:total protein (TP) ratio, Trolox equivalent antioxidant capacity (TEAC), uric acid (UA) in plasma, and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in erythrocytes. Results: Immediately postrace, there were significant increases in CD, AOPP, TEAC, UA (for all P < 0.001), and AOPP:TP (P < 0.01). MDA rose significantly (P < 0.01) 1 d postrace, whereas CD (P < 0.01), AOPP (P = 0.01), AOPP:TP (P < 0.05), and TEAC (P < 0.001) remained elevated. OxLDL:LDL trended to increase, whereas oxLDL significantly (P < 0.01) decreased 1 d postrace. Except for GSH-Px (P = 0.08), activities of SOD (P < 0.001) and CAT (P < 0.05) significantly decreased postrace. All oxidative stress markers had returned to prerace values 5 d postrace. Furthermore, several relationships between training status and oxidative stress markers, TEAC, and antioxidant enzyme activities were noted. Conclusions: This study indicates that despite a temporary increase in most (but not all) oxidative stress markers, there is no persistent oxidative stress in response to an ironman triathlon, probably due to training- and exercise-induced protective alterations in the antioxidant defense system.

The characterisation of Ureaplasma species isolated from the Chorioamnion of women who deliver late Preterm

This thesis investigated, for the first time, the prevalence of Ureaplasma species infection within the placentae of women who delivered in the late preterm stages of pregnancy. The presence of these microorganisms was associated with either severe inflammation within the placenta or, for some women, there were no pregnancy complications and these women delivered at term. Ureaplasmas are able to vary their surface exposed lipoproteins and we demonstrated that different host immune responses were generated in vivo to different sized surface lipoproteins. This may explain why ureaplasma infections do not always result in adverse pregnancy and neonatal outcomes.

The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood

Bone mass acquired during childhood is the primary determinant of adult bone mineral density (BMD) and osteoporosis risk. Bone accrual is subject to genetic influences. Activating and inactivating LRP5 gene mutations elicit extreme bone phenotypes, while more common LRP5 polymorphisms are associated with normal variation of BMD. Our aim was to test the hypothesis that LRP5 gene polymorphisms influence bone mass acquisition during childhood. The association between LRP5 gene polymorphisms and bone size and mineralization was examined in 819 unrelated British Caucasian children (n = 429 boys) aged 9 years. Height, weight, pubertal status (where available), total-body and spinal bone area, bone mineral content (BMC), BMD, and area-adjusted BMC (aBMC) were assessed. Dual-energy X-ray absorptiometry (DXA)-gene associations were assessed by linear regression, with adjustment for age, gender, pubertal status, and body size parameters. There were 140, 79, 12, and 2 girls who achieved Tanner stages I-IV, respectively, and 179 and 32 boys who achieved Tanner stages I and II, respectively. The rs2306862 (N740N) coding polymorphism in exon 10 of the LRP5 gene was associated with spinal BMD and aBMC (each P = 0.01) and total-body BMD and aBMC (P = 0.04 and 0.03, respectively). Adjusting for pubertal stage strengthened associations between this polymorphism and spinal BMD and aBMC (P = 0.01 and 0.002, respectively). Individuals homozygous for the T allele had greater spinal BMD and aBMC scores than those homozygous for the C allele. A dose effect was apparent as the mean spinal BMD and aBMC of heterozygous TC individuals were intermediate between those of their TT and CC counterparts. The N740N polymorphism in exon 10 of LRP5 was associated with spinal BMD and aBMC in pre- and early pubertal children. These results indicate that LRP5 influences volumetric bone density in childhood, possibly through effects on trabecular bone formation.

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: A Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1α and IL-1β); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0·22 SD (95% CI 0·18–0·25; 12·5%; p=9·3 × 10−33), concentrations of interleukin 6 decreased by 0·02 SD (−0·04 to −0·01; −1·7%; p=3·5 × 10−3), and concentrations of C-reactive protein decreased by 0·03 SD (−0·04 to −0·02; −3·4%; p=7·7 × 10−14). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1·15 (1·08–1·22; p=1·8 × 10−6) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1·03 (1·02–1·04; p=3·9 × 10−10). Per-allele odds ratios were 0·97 (0·95–0·99; p=9·9 × 10−4) for rheumatoid arthritis, 0·99 (0·97–1·01; p=0·47) for type 2 diabetes, 1·00 (0·98–1·02; p=0·92) for ischaemic stroke, and 1·08 (1·04–1·12; p=1·8 × 10−5) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Funding UK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7.

Genetic disorders of the LRP5-Wnt signalling pathway affecting the skeleton

Osteoporosis is a common, increasingly prevalent and potentially debilitating condition of men and women. Genetic factors are major determinants of bone mass and the risk of fracture, but few genes have been definitively demonstrated to be involved. The identification of these factors will provide novel insights into the processes of bone formation and loss and thus the pathogenesis of osteoporosis, enabling the rational development of novel therapies. In this article, we present the extensive genetic and functional data indicating that the LRP5 gene and the Wnt signalling pathway are key players in bone formation and the risk of osteoporosis, and that LRP5 signalling is essential for normal morphology, developmental processes and bone health.