Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells

The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor（GM-CSF）, monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.

Waist circumference cut-off values for the prediction of cardiovascular risk factors clustering in Chinese school-aged children : a cross-sectional study

Background: Waist circumference has been identified as a valuable predictor of cardiovascular risk in children. The development of waist circumference percentiles and cut-offs for various ethnic groups are necessary because of differences in body composition. The purpose of this study was to develop waist circumference percentiles for Chinese children and to explore optimal waist circumference cut-off values for predicting cardiovascular risk factors clustering in this population.----- ----- Methods: Height, weight, and waist circumference were measured in 5529 children (2830 boys and 2699 girls) aged 6-12 years randomly selected from southern and northern China. Blood pressure, fasting triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and glucose were obtained in a subsample (n = 1845). Smoothed percentile curves were produced using the LMS method. Receiver-operating characteristic analysis was used to derive the optimal age- and gender-specific waist circumference thresholds for predicting the clustering of cardiovascular risk factors.----- ----- Results: Gender-specific waist circumference percentiles were constructed. The waist circumference thresholds were at the 90th and 84th percentiles for Chinese boys and girls respectively, with sensitivity and specificity ranging from 67% to 83%. The odds ratio of a clustering of cardiovascular risk factors among boys and girls with a higher value than cut-off points was 10.349 (95% confidence interval 4.466 to 23.979) and 8.084 (95% confidence interval 3.147 to 20.767) compared with their counterparts.----- ----- Conclusions: Percentile curves for waist circumference of Chinese children are provided. The cut-off point for waist circumference to predict cardiovascular risk factors clustering is at the 90th and 84th percentiles for Chinese boys and girls, respectively.

The molecular mechanisms utilised by mesenchymal stem cells in migration to acute myocardial infarction

Heart damage caused by acute myocardial infarction (AMI) is a leading cause of death and disability in Australia. Novel therapies are still required for the treatment of this condition due to the poor reparative ability of the heart. As such, cellular therapies that assist in the recovery of heart muscle are of great current interest. Culture expanded mesenchymal stem cells (MSC) represent a stem and progenitor cell population that has been shown to promote tissue recovery in pre-clinical studies of AMI. For MSC-based therapies in the clinic, an intravenous route of administration would ideally be used due to the low cost, ease of delivery and relative safety. The study of MSC migration is therefore clinically relevant for a minimally invasive cell therapy to promote regeneration of damaged tissue. C57BL/6, UBI-GFP-BL/6 and CD44-/-/GFP+/+ mice were utilised to investigate mMSC migration. To assist in murine models of MSC migration, a novel method was used for the isolation of murine MSC (mMSC). These mMSC were then expanded in culture and putative mMSC were positive for Sca-1, CD90.2, and CD44 and were negative for CD45 and CD11b. Furthermore, mMSC from C57BL/6 and UBI-GFP-BL/6 mice were shown to differentiate into cells of the mesodermal lineage. Cells from CD44-/-/GFP+/+ mice were positive for Sca-1 and CD90.2, and negative for CD44, CD45 and CD11b however, these cells were unable to differentiate into adipocytes and chondrocytes and express lineage specific genes, PLIN and ACAN. Analysis of mMSC chemokine receptor (CR) expression showed that although mMSC do express chemokine receptors, (including those specific for chemokines released after AMI), these were low or undetectable by mRNA. However, protein expression could be detected, which was predominantly cytoplasmic. It was further shown that in both healthy (unperturbed) and inflamed tissues, mMSC had very little specific migration and engraftment after intravenous injection. To determine if poor mMSC migration was due to the inability of mMSC to respond to chemotactic stimuli, chemokine expression in bone marrow, skin injury and hearts (healthy and after AMI) was analysed at various time points by quantitative real-time PCR (qRT PCR). Many chemokines were up-regulated after skin biopsy and AMI, but the highest acute levels were found for CXCL12 and CCL7. Due to their high expression in infarcted hearts, the chemokines CXCL12 and CCL7 were tested for their effect on mMSC migration. Despite CR expression at both protein and mRNA levels, migration in response to CXCL12 and CCL7 was low in mMSC cultured on Nunclon plastic. A novel tissue culture plastic technology (UpCellTM) was then used that allowed gentle non-enzymatic dissociation of mMSC, thus preserving surface expression of the CRs. Despite this the in vitro data indicated that CXCL12 fails to induce significant migration ability of mMSC, while CCL7 induces significant, but low-level migration. We speculated this may be because of low levels of surface expression of chemokine receptors. In a strategy to increase cell surface expression of mMSC chemokine receptors and enhance their in vitro and in vivo migration capacity, mMSC were pre-treated with pro-inflammatory cytokines. Increased levels of both mRNA and surface protein expression were found for CRs by pre-treating mMSC with pro-inflammatory cytokines including TNF-á, IFN-ã, IL-1á and IL-6. Furthermore, the chemotactic response of mMSC to CXCL12 and CCL7 was significantly higher with these pretreated cells. Finally, the effectiveness of this type of cell manipulation was demonstrated in vivo, where mMSC pre-treated with TNF-á and IFN-ã showed significantly increased migration in skin injury and AMI models. Therefore this thesis has demonstrated, using in vitro and in vivo models, the potential for prior manipulation of MSC as a possible means for increasing the utility of intravenously delivery for MSC-based cellular therapies.

Relationships between preventive activities, psychosocial factors and recurrence of venous leg ulcers : a prospective study

Aim To identify relationships between preventive activities, psychosocial factors and leg ulcer recurrence in patients with chronic venous leg ulcers. Background Chronic venous leg ulcers are slow to heal and frequently recur, resulting in years of suffering and intensive use of health care resources. Methods A prospective longitudinal study was undertaken with a sample of 80 patients with a venous leg ulcer recruited when their ulcer healed. Data were collected from 2006–2009 from medical records on demographics, medical history and ulcer history; and from self-report questionnaires on physical activity, nutrition, preventive activities and psychosocial measures. Follow-up data were collected via questionnaires every three months for 12 months after healing. Median time to recurrence was calculated using the Kaplan-Meier method. A Cox proportional-hazards regression model was used to adjust for potential confounders and determine effects of preventive strategies and psychosocial factors on recurrence. Results: There were 35 recurrences in a sample of 80 participants. Median time to recurrence was 27 weeks. After adjustment for potential confounders, a Cox proportional hazards regression model found that at least an hour/day of leg elevation, six or more days/week in Class 2 (20–25mmHg) or 3 (30–40mmHg) compression hosiery, higher social support scale scores and higher General Self-Efficacy scores remained significantly associated (p<0.05) with a lower risk of recurrence, while male gender and a history of DVT remained significant risk factors for recurrence. Conclusion Results indicate that leg elevation, compression hosiery, high levels of self-efficacy and strong social support will help prevent recurrence.

A Raman spectroscopic study of bukovskýite Fe2(AsO4)(SO4)(OH)•7H2O-a mineral phase with a significant role in arsenic migration

The Raman spectrum of bukovskýite, Fe3+2(OH)(SO4)(AsO4)•7H2O has been studied and compared with the Raman spectrum of an amorphous gel containing specifically Fe, As and S elements and is understood as an intermediate product in the formation of bukovskýite. Observed bands are assigned to the stretching and bending vibrations of (SO4)2- and (AsO4)3- units, stretching and bending vibrations and librational modes of hydrogen bonded water molecules, stretching and bending vibrations of hydrogen bonded (OH)- ions and Fe3+-(O,OH) units. Approximate range of O-H...O hydrogen bond lengths is inferred from the Raman spectra. Raman spectra of crystalline bukovskýite and of the amorphous gel differ in that the bukovskýite spectrum is more complex, observed bands are sharp, the degenerate bands of (SO4)2- and (AsO4)3- are split and more intense. Lower wavenumbers of  H2O bending vibration in the spectrum of the amorphous gel may indicate the presence of weaker hydrogen bonds compared with those in bukovskýite.

Characteristics of utility cyclists in Queensland, Australia : an examination of the associations between individual, social and environmental factors and utility cycling

Background: Initiatives to promote utility cycling in countries like Australia and the US, which have low rates of utility cycling, may be more effective if they first target recreational cyclists. This study aimed to describe patterns of utility cycling and examine its correlates, among cyclists in Queensland, Australia. Methods: An online survey was administered to adult members of a state-based cycling community and advocacy group (n=1813). The survey asked about demographic characteristics and cycling behavior, motivators and constraints. Utility cycling patterns were described, and logistic regression modeling was used to examine associations between utility cycling and other variables. Results: Forty-seven percent of respondents reported utility cycling: most did so to commute (86%). Most journeys (83%) were >5 km. Being male, younger, employed full-time, or university-educated increased the likelihood of utility cycling (p<0.05). Perceiving cycling to be a cheap or a convenient form of transport were associated with utility cycling (p<0.05). Conclusions: The moderate rate of utility cycling among recreational cyclists highlights a potential to promote utility cycling among this group. To increase utility cycling, strategies should target female and older recreational cyclists and focus on making cycling a cheap and convenient mode of transport.

A Bayesian approach to assess interaction between known risk factors: The risk of lung cancer from exposure to asbestos and smoking

We review the literature on the combined effect of asbestos exposure and smoking on lung cancer, and explore a Bayesian approach to assess evidence of interaction. Previous approaches have focussed on separate tests for an additive or multiplicative relation. We extend these approaches by exploring the strength of evidence for either relation using approaches which allow the data to choose between both models. We then compare the different approaches.

A cell migration device that maintains a defined surface with no cellular damage during wound edge generation

Studying the rate of cell migration provides insight into fundamental cell biology as well as a tool to assess the functionality of synthetic surfaces and soluble environments used in tissue engineering. The traditional tools used to study cell migration include the fence and wound healing assays. In this paper we describe the development of a microchannel based device for the study of cell migration on defined surfaces. We demonstrate that this device provides a superior tool, relative to the previously mentioned assays, for assessing the propagation rate of cell wave fronts. The significant advantage provided by this technology is the ability to maintain a virgin surface prior to the commencement of the cell migration assay. Here, the device is used to assess rates of mouse fibroblasts (NIH 3T3) and human osteosarcoma (SaOS2) cell migration on surfaces functionalized with various extracellular matrix proteins as a demonstration that confining cell migration within a microchannel produces consistent and robust data. The device design enables rapid and simplistic assessment of multiple repeats on a single chip, where surfaces have not been previously exposed to cells or cellular secretions.

An examination of the relationships between lifestyle factors and mental health among Australian midlife and older women

Background It is well known that lifestyle factors including overweight/obesity, physical inactivity, smoking and alcohol use are largely related with morbidity and mortality of chronic diseases including diabetes and cardiovascular diseases. The effect of lifestyle factors on people’s mental health who have a chronic disease is less defined in the research. The World Health Organisation has defined health as “a state of complete physical, mental and social well-being”. It is important, therefore to develop an understanding of the relationships between lifestyle and mental health as this may have implications for maximising the efficacy of health promotion in people with chronic diseases. Objectives The overall aim of the research was to examine the relationships between lifestyle factors and mental health among Australian midlife and older women. Methodology The current research measured four lifestyle factors including weight status, physical activity, smoking and alcohol use. Three interconnecting studies were undertaken to develop a comprehensive understanding of the relationships between lifestyle factors and mental health. Study 1 investigated the longitudinal effect of lifestyle factors on mental health by using midlife and older women randomly selected from the community. Study 2 adopted a cross-sectional design, and compared the effect of lifestyle factors on mental health between midlife and older women with and without diabetes. Study 3 examined the mediating effect of self-efficacy in the relationships between lifestyle factors and mental health among midlife and older women with diabetes. A questionnaire survey was chosen as the means to gather information, and multiple linear regression analysis was conducted as the primary statistical approach. Results The research showed that the four lifestyle factors including weight status, physical activity, smoking and alcohol use did impact on mental health among Australian midlife and older women. First, women with a higher BMI had lower levels of mental health than women with normal weight, but as women age, the mental health of women who were overweight and obese becomes better than that of women with normal weight. Second, women who were physically active had higher levels of mental health than those who were not. Third, smoking adversely impacted on women’s mental health. Finally, those who were past-drinkers had less anxiety symptoms than women who were non-drinkers as they age. Women with diabetes appeared to have lower levels of mental health compared to women without. However, the disparities of mental health between two groups were confounded by low levels of physical activity and co-morbidities. This finding underlines the effect of physical activity on women’s mental health, and highlights the potential of reducing the gap of mental health by promoting physical activity. In addition, self-efficacy was shown to be the mediator of the relationships between BMI, physical activity and depression, suggesting that enhancing people’s self-efficacy may be useful for mental health improvement. Conclusions In conclusion, Australian midlife and older women who live with a healthier lifestyle have higher levels of mental health. It is suggested that strategies aiming to improve people’s mental health may be more effective if they focus on enhancing people’s self-efficacy levels. This study has implications to both health education and policy development. It indicates that health professionals may need to consider clients’ mental health as an integrated part of lifestyle changing process. Furthermore, given that lifestyle factors impact on both physical and mental health, lifestyle modification should continue to be the focus of policy development.

A systematic review of environmental factors and obesogenic dietary intakes among adults : are we getting closer to understanding obesogenic environments?

This study examined whether physical, social, cultural and economical environmental factors are associated with obesogenic dietary behaviours and overweight/obesity among adults. Literature searches of databases (i.e. PubMed, CSA Illumina, Web of Science, PsychInfo) identified studies examining environmental factors and the consumption of energy, fat, fibre, fruit, vegetables, sugar-sweetened drinks, meal patterns and weight status. Twenty-eight studies were in-scope, the majority (n= 16) were conducted in the USA. Weight status was consistently associated with the food environment; greater accessibility to supermarkets or less access to takeaway outlets were associated with a lower BMI or prevalence of overweight/obesity. However, obesogenic dietary behaviours did not mirror these associations; mixed associations were found between the environment and obesogenic dietary behaviours. Living in a socioeconomically-deprived area was the only environmental factor consistently associated with a number of obesogenic dietary behaviours. Associations between the environment and weight status are more consistent than that seen between the environment and dietary behaviours. The environment may play an important role in the development of overweight/obesity, however the dietary mechanisms that contribute to this remain unclear and the physical activity environment may also play an important role in weight gain, overweight and obesity.