Modulation of LPS-induced chorioamnionitis by ureaplasma parvum in sheep chorioamnionitis in sheep

ABSTRACT Objective: Ureaplasma parvum colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that ureaplasma colonization of amniotic fluid will modulate chorioamnionitis induced by E.coli lipopolysaccharide (LPS). Methods: Sheep received intra-amniotic (IA) injections of media (control) or live ureaplasma either 7 or 70d before delivery. Another group received IA LPS 2d before delivery. To test for interactions, U.parvum exposed animals were challenged with IA LPS, and delivered 2d later. All animals were delivered preterm at 125±1 day gestation. Results: Both IA ureaplasmas and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of pro-inflammatory cytokines and myeloperoxidase in leukocytes, while ureaplasmas alone caused modest responses. Interestingly, 7d but not 70d ureaplasma exposure significantly downregulated LPS induced pro-inflammatory cytokines and myeloperoxidase expression in the chorioamnion. Conclusion: U.parvum can suppress LPS induced experimental chorioamnionitis.

Alternative models of cardiac rehabilitation : a systematic review

The traditional hospital-based model of cardiac rehabilitation faces substantial challenges, such as cost and accessibility. These challenges have led to the development of alternative models of cardiac rehabilitation in recent years. The aim of this study was to identify and critique evidence for the effectiveness of these alternative models. A total of 22 databases were searched to identify quantitative studies or systematic reviews of quantitative studies regarding the effectiveness of alternative models of cardiac rehabilitation. Included studies were appraised using a Critical Appraisal Skills Programme tool and the National Health and Medical Research Council's designations for Level of Evidence. The 83 included articles described interventions in the following broad categories of alternative models of care: multifactorial individualized telehealth, internet based, telehealth focused on exercise, telehealth focused on recovery, community- or home-based, and complementary therapies. Multifactorial individualized telehealth and community- or home-based cardiac rehabilitation are effective alternative models of cardiac rehabilitation, as they have produced similar reductions in cardiovascular disease risk factors compared with hospital-based programmes. While further research is required to address the paucity of data available regarding the effectiveness of alternative models of cardiac rehabilitation in rural, remote, and culturally and linguistically diverse populations, our review indicates there is no need to rely on hospital-based strategies alone to deliver effective cardiac rehabilitation. Local healthcare systems should strive to integrate alternative models of cardiac rehabilitation, such as brief telehealth interventions tailored to individual's risk factor profiles as well as community- or home-based programmes, in order to ensure there are choices available for patients that best fit their needs, risk factor profile, and preferences.

A novel device using the Nordic hamstring exercise to assess eccentric knee flexors strength : a reliability and retrospective injury study

STUDY DESIGN: Reliability and case-control injury study. OBJECTIVES: 1) To determine if a novel device, designed to measure eccentric knee flexors strength via the Nordic hamstring exercise (NHE), displays acceptable test-retest reliability; 2) to determine normative values for eccentric knee flexors strength derived from the device in individuals without a history of hamstring strain injury (HSI) and; 3) to determine if the device could detect weakness in elite athletes with a previous history of unilateral HSI. BACKGROUND: HSIs and reinjuries are the most common cause of lost playing time in a number of sports. Eccentric knee flexors weakness is a major modifiable risk factor for future HSIs, however there is a lack of easily accessible equipment to assess this strength quality. METHODS: Thirty recreationally active males without a history of HSI completed NHEs on the device on 2 separate occasions. Intraclass correlation coefficients (ICCs), typical error (TE), typical error as a co-efficient of variation (%TE), and minimum detectable change at a 95% confidence interval (MDC95) were calculated. Normative strength data were determined using the most reliable measurement. An additional 20 elite athletes with a unilateral history of HSI within the previous 12 months performed NHEs on the device to determine if residual eccentric muscle weakness existed in the previously injured limb. RESULTS: The device displayed high to moderate reliability (ICC = 0.83 to 0.90; TE = 21.7 N to 27.5 N; %TE = 5.8 to 8.5; MDC95 = 76.2 to 60.1 N). Mean±SD normative eccentric flexors strength, based on the uninjured group, was 344.7 ± 61.1 N for the left and 361.2 ± 65.1 N for the right side. The previously injured limbs were 15% weaker than the contralateral uninjured limbs (mean difference = 50.3 N; 95% CI = 25.7 to 74.9N; P < .01), 15% weaker than the normative left limb data (mean difference = 50.0 N; 95% CI = 1.4 to 98.5 N; P = .04) and 18% weaker than the normative right limb data (mean difference = 66.5 N; 95% CI = 18.0 to 115.1 N; P < .01). CONCLUSIONS: The experimental device offers a reliable method to determine eccentric knee flexors strength and strength asymmetry and revealed residual weakness in previously injured elite athletes.

Urinary biomolecular indicators of exercise-induced over exertion injury

Poor health and injury represent major obstacles to the future economic security of Australia. The national economic cost of work-related injury is estimated at $57.5 billion p/a. Since exposure to high physical demands is a major risk factor for musculoskeletal injury, monitoring and managing such physical activity levels in workers is a potentially important injury prevention strategy. Current injury monitoring practices are inadequate for the provision of clinically valuable information about the tissue specific responses to physical exertion. Injury of various soft tissue structures can manifest over time through accumulation of micro-trauma. Such micro-trauma has a propensity to increase the risk of acute injuries to soft-tissue structures such as muscle or tendon. As such, the capacity to monitor biomarkers that result from the disruption of these tissues offers a means of assisting the pre-emptive management of subclinical injury prior to acute failure or for evaluation of recovery processes. Here we have adopted an in-vivo exercise induced muscle damage model allowing the application of laboratory controlled conditions to assist in uncovering biochemical indicators associated with soft-tissue trauma and recovery. Importantly, urine was utilised as the diagnostic medium since it is non-invasive to collect, more acceptable to workers and less costly to employers. Moreover, it is our hypothesis that exercise induced tissue degradation products enter the circulation and are subsequently filtered by the kidney and pass through to the urine. To test this hypothesis a range of metabolomic and proteomic discovery-phase techniques were used, along with targeted approaches. Several small molecules relating to tissue damage were identified along with a series of skeletal muscle-specific protein fragments resulting from exercise induced soft-tissue damage. Each of the potential biomolecular markers appeared to be temporally present within urine. Moreover, the regulation of abundance seemed to be associated with functional recovery following the injury. This discovery may have important clinical applications for monitoring of a variety of inflammatory myopathies as well as novel applications in monitoring of the musculoskeletal health status of workers, professional athletes and/or military personnel to reduce the onset of potentially debilitating musculoskeletal injuries within these professions.

Sleepy driving and pulling over for a rest : investigating individual factors that contribute to these driving behaviours

Driver sleepiness is a substantial crash risk factor and as such, is a major contributor to crash statistics. A number of individual factors (i.e., psychological factors) have been suggested to influence driving while sleepy. However, few studies have examined the influence of these individual factors for sleepy driving in combination. The current study sought to examine how various demographic factors, attitudes, perceived legitimacy, personality constructs, and risk taking variables were associated with self-reported likelihood of driving sleepy and pulling over and resting when sleepy. The results show that being a younger driver, having positive attitudes towards driving sleepy, and high levels of emotional stability were related to self-reported likelihood of driving sleepy. Whereas, being an older driver and having negative attitudes towards driving sleepy were associated with self-reported likelihood of pulling over and resting when sleepy. Overall, the obtained results suggest that the age and attitudes of the driver have greater influence than personality traits or risk taking factors. Campaigns focused on changing attitudes to reflect the dangerousness of sleepy driving could be important for road safety outcomes.

Social influences and the physical activity intentions of parents of young-children families: An extended Theory of Planned Behavior Approach

Evidence within Australia and internationally suggests parenthood as a risk factor for inactivity; however, research into understanding parental physical activity is scarce. Given that active parents can create active families and social factors are important for parents’ decision making, the authors investigated a range of social influences on parents’ intentions to be physically active. Parents (N = 580; 288 mothers and 292 fathers) of children younger than 5 years completed an extended Theory of Planned Behavior questionnaire either online or paper based. For both genders, attitude, control factors, group norms, friend general support, and an active parent identity predicted intentions, with social pressure and family support further predicting mothers’ intentions and active others further predicting fathers’ intentions. Attention to these factors and those specific to the genders may improve parents’ intentions to be physically active, thus maximizing the benefits to their own health and the healthy lifestyle practices for other family members.

The next generation health intervention tool - Can smart phone applications help young people track and moderate alcohol use and potential harms?

Whilst alcohol is a common feature of many social gatherings, there are numerous immediate and long-term health and social harms associated with its abuse. Alcohol consumption is the world’s third largest risk factor for disease and disability with almost 4% of all deaths worldwide attributed to alcohol. Not surprisingly, alcohol use and binge drinking by young people is of particular concern with Australian data reporting that 39% of young people (18-19yrs) admitted drinking at least weekly and 32% drank to levels that put them at risk of alcohol-related harm. The growing market penetration and connectivity of smartphones may be an opportunities for innovation in promoting health-related self-management of substance use. However, little is known about how best to harness and optimise this technology for health-related intervention and behaviour change. This paper explores the utility and interface of smartphone technology as a health intervention tool to monitor and moderate alcohol use. A review of the psychological health applications of this technology will be presented along with the findings of a series of focus groups, surveys and behavioural field trials of several drink-monitoring applications. Qualitative and quantitative data will be presented on the perceptions, preferences and utility of the design, usability and functionality of smartphone apps to monitoring and moderate alcohol use. How these findings have shaped the development and evolution of the OnTrack app will be specifically discussed, along with future directions and applications of this technology in health intervention, prevention and promotion.

Serum 25-hydroxyvitamin D concentration in relation to melanoma progress

Dr Wyatt’s study investigated the complex relationship between vitamin D and melanoma, specifically if vitamin D status is associated with more aggressive melanomas. Exposure to solar ultraviolet radiation is the principal risk factor for melanoma and also the main source of vitamin D. This research found that insufficient vitamin D at time of melanoma diagnosis is significantly associated with poorer prognosis (as defined by tumour thickness). These results will contribute to a more refined public health message concerning melanoma and vitamin D, particularly in Queensland, which has the highest global incidence of melanoma, but vitamin D deficiency is not uncommon.

Role of the apolipoprotein E and catechol-O-methyltransferase genes in prospective and retrospective memory traits

Human memory is a complex neurocognitive process. By combining psychological and molecular genetics expertise, we examined the APOE ε4 allele, a known risk factor for Alzheimer's disease, and the COMT Val 158 polymorphism, previously implicated in schizophrenia, for association with lowered memory functioning in healthy adults. To assess memory type we used a range of memory tests of both retrospective and prospective memory. Genotypes were determined using RFLP analysis and compared with mean memory scores using univariate ANOVAs. Despite a modest sample size (n=197), our study found a significant effect of the APOE ε4 polymorphism in prospective memory. Supporting our hypothesis, a significant difference was demonstrated between genotype groups for means of the Comprehensive Assessment of Prospective Memory total score (p=0.036; ε4 alleles=1.99; all other alleles=1.86). In addition, we demonstrate a significant interactive effect between the APOE ε4 and COMT polymorphisms in semantic memory. This is the first study to investigate both APOE and COMT genotypes in relation to memory in non-pathological adults and provides important information regarding the effect of genetic determinants on human memory.

Analysis of the MTHFR C677T variant with migraine phenotypes

Background The methylenetetrahydrofolate reductase (MTHFR) gene variant C677T has been implicated as a genetic risk factor in migraine susceptibility, particularly in Migraine with Aura. Migraine, with and without aura (MA and MO) have many diagnostic characteristics in common. It is postulated that migraine symptomatic characteristics might themselves be influenced by MTHFR. Here we analysed the clinical profile, migraine symptoms, triggers and treatments of 267 migraineurs previously genotyped for the MTHFR C677T variant. The chi-square test was used to analyse all potential relationships between genotype and migraine clinical variables. Regression analyses were performed to assess the association of C677T with all migraine clinical variables after adjusting for gender. Findings The homozygous TT genotype was significantly associated with MA (P < 0.0001) and unilateral head pain (P = 0.002). While the CT genotype was significantly associated with physical activity discomfort (P < 0.001) and stress as a migraine trigger (P = 0.002). Females with the TT genotype were significantly associated with unilateral head pain (P < 0.001) and females with the CT genotype were significantly associated with nausea (P < 0.001), osmophobia (P = 0.002), and the use of natural remedy for migraine treatment (P = 0.003). Conversely, male migraineurs with the TT genotype experienced higher incidences of bilateral head pain (63% vs 34%) and were less likely to use a natural remedy as a migraine treatment compared to female migraineurs (5% vs 20%). Conclusions MTHFR genotype is associated with specific clinical variables of migraine including unilateral head pain, physical activity discomfort and stress.

Novel NOD2 haplotype strengthens the association between TLR4 Asp299gly and Crohnʼs disease in an Australian population

Background:: The first major Crohn's disease (CD) susceptibility gene, NOD2, implicates the innate intestinal immune system and other pattern recognition receptors in the pathogenesis of this chronic, debilitating disorder. These include the Toll‐like receptors, specifically TLR4 and TLR5. A variant in the TLR4 gene (A299G) has demonstrated variable association with CD. We aimed to investigate the relationship between TLR4 A299G and TLR5 N392ST, and an Australian inflammatory bowel disease cohort, and to explore the strength of association between TLR4 A299G and CD using global meta‐analysis. Methods:: Cases (CD = 619, ulcerative colitis = 300) and controls (n = 360) were genotyped for TLR4 A299G, TLR5 N392ST, and the 4 major NOD2 mutations. Data were interrogated for case‐control analysis prior to and after stratification by NOD2 genotype. Genotype–phenotype relationships were also sought. Meta‐analysis was conducted via RevMan. Results:: The TLR4 A299G variant allele showed a significant association with CD compared to controls (P = 0.04) and a novel NOD2 haplotype was identified which strengthened this (P = 0.003). Furthermore, we identified that TLR4 A299G was associated with CD limited to the colon (P = 0.02). In the presence of the novel NOD2 haplotype, TLR4 A299G was more strongly associated with colonic disease (P < 0.001) and nonstricturing disease (P = 0.009). A meta‐analysis of 11 CD cohorts identified a 1.5‐fold increase in risk for the variant TLR4 A299G allele (P < 0.00001). Conclusions:: TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease. Furthermore, we identified a novel NOD2 haplotype that strengthens the relationship between TLR4 A299G and these phenotypes.

Genetic investigation of methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) in multiple sclerosis

Multiple sclerosis (MS) is a chronic neurological disease characterized by central nervous system (CNS) inflammation and demyelination. The C677T substitution variant in the methylenetetrahydrofolate reductase (MTHFR) gene has been associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Higher blood levels of homocysteine have also been reported in MS. Thus, the C677T mutation of the MTHFR gene may influence MS susceptibility. Noradrenaline, a neurotransmitter believed to play an immunosupressive role in neuroinflammatory disorders, is catabolized by catechol-O-methyl transferase (COMT). The COMT G158A substitution results in a three- to four-fold decreased activity of the COMT enzyme, which may influence CNS synaptic catecholamine breakdown and could also play a role in MS inflammation. We tested DNA from Australian MS patients and unaffected control subjects, matched for gender, age and ethnicity. Specifically, we genotyped the MTHFR C677T and the COMT G158A mutations. Genotype distributions showed that the homozygous mutant MTHFR genotype (T/T) and the COMT (H/H) genotype were slightly over-represented in the MS group (16% versus 11% and 24% versus 19%, respectively), but both variations failed to reach statistical significance (P=0.15 and P=0.32, respectively). Hence, results from the present study do not support a major role for either functional gene mutation in MS susceptibility.

Phenotypical characterisation of the isolated Norfolk Island population focusing on epidemiological indicators of cardiovascular disease

Objectives Only 193 people from Pitcairn Island, all descended from 9 ‘Bounty’ mutineers and 12 Tahitian women, moved to the uninhabited Norfolk Island in 1856. Our objective was to assess the population of Norfolk Island, several thousand km off the eastern coast of Australia, as a genetic isolate of potential use for cardiovascular disease (CVD) gene mapping. Methods A total of 602 participants, approximately two thirds of the island’s present adult population, were characterized for a panel of CVD risk factors. Statistical power and heritability were calculated. Results Norfolk Islander’s possess an increased prevalence of hypertension, obesity and multiple CVD risk factors when compared to outbred Caucasian populations. 64% of the study participants were descendents of the island’s original founder population. Triglycerides, cholesterol, and blood pressures all had heritabilities above 0.2. Conclusions The Norfolk land population is a potentially useful genetic isolate for gene mapping studies aimed at identifying CVD risk factor quantitative trait loci (QTL).

The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura

Background The C677T variant in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that may also be affected by genetically influenced hyperhomocysteinaemia. To determine whether the C677T variant in the MTHFR gene is associated with migraine susceptibility we utilised unrelated and family-based case-control study designs. Methods A total of 652 Caucasian migraine cases were investigated in this study. The MTHFR C677T variant was genotyped in 270 unrelated migraine cases and 270 controls as well as 382 affected subjects from 92 multiplex pedigrees. Results In the unrelated case-control sample we observed an over-representation of the 677T allele in migraine patients compared to controls, specifically for the MA subtype (40% vs. 33%) (χ2 = 5.70, P = 0.017). The Armitage test for trend indicated a significant dosage effect of the risk allele (T) for MA (χ2 = 5.72, P = 0.017). This linear trend was also present in the independent family-based sample (χ2 = 4.25, Padjusted = 0.039). Overall, our results indicate that the T/T genotype confers a modest, yet significant, increase in risk for the MA subtype (odds ratio: 2.0 – 2.5). No increased risk for the MO subtype was observed (P > 0.05). Conclusions In Caucasians, the C677T variant in the MTHFR gene influences susceptibility to MA, but not MO. Investigation into the enzyme activity of MTHFR and the role of homocysteine in the pathophysiology of migraine is warranted.

Perceived barriers to healthy lifestyle activities in midlife and older Australian women with type 2 diabetes

Background Type 2 diabetes is a leading cause of morbidity and mortality in midlife and older Australian women with known modifiable risk factors for type 2 diabetes including smoking, nutrition, physical activity and obesity. In Australia little research has been done to investigate the perceived barriers to healthy lifestyle activities in midlife and older women with type 2 diabetes. Aims The primary aim of this study was to explore the level and type of perceived barriers to health promotion activities. The secondary aim was to explore the relationship of perceived barriers to smoking behaviour, fruit and vegetable intake, physical activity, and body mass index. Methods The study was a cross sectional survey of women, aged over 45 with type 2 diabetes, recruited from four metropolitan community health clinics (n = 41). Data were collected from self-report questionnaires and analysed using quantitative methods. Results Women in the study had average total barriers scores similar to those reported in the literature for women with a range of physical disabilities and illnesses. The leading barriers for this group of women were: lack of interest, concern about safety, too tired, lack of money and feeling what they do does not help. There was no association between total barriers scores and body mass index, physical activity, fruit and vegetable intake or socio-demographic variables. Conclusion This study contributes to understanding the perceptions of midlife and older women with type 2 diabetes about the level and type of barriers to healthy lifestyle activities that they experience. The participants reported a high level perceived barriers with a range of personal, social and environmental issues identified and described. This study suggests that health promotion education and interventions for risk factor reduction in women with type 2 diabetes may be enhanced by explicitly addressing perceived barriers to healthy lifestyle activities.