Association study of calcitonin gene-related polypeptide-alpha (CALCA) gene polymorphism with migraine

Migraine is a neurological disorder that is associated with increased levels of calcitonin gene-related peptide (CGRP) in plasma. CGRP, being one of the mediators of neurogenic inflammation and a phenomenon implicated in the pathogenesis of migraine headache, is thus suggested to have an important role in migraine pathophysiology. Polymorphisms of the CALCA gene have been linked to Parkinson's disease, ovarian cancer and essential hypertension, suggesting a functional role for these polymorphisms. Given the strong evidence linking CGRP and migraine, it is hypothesised that polymorphisms in the CALCA gene may play a role in migraine pathogenesis. Seemingly non functional intronic polymorphisms are capable of disrupting normal RNA processing or introducing a splice site in the transcript. A 16 bp deletion in the first intron of the CALCA gene has been reported to be a good match for the binding site for a transcription factor expressed strongly in neural crest derived cells, AP-2. This deletion also eliminates an intron splicing enhancer (ISE) that may potentially cause exon skipping. This study investigated the role of the 16 bp intronic deletion in the CALCA gene in migraineurs and matched control individuals. Six hundred individuals were genotyped for the deletion by polymerase chain reaction followed by fragment analysis on the 3130 Genetic Analyser. The results of this study showed no significant association between the intronic 16 bp deletion in the CALCA gene and migraine in the tested Australian Caucasian population. However, given the evidence linking CGRP and migraine, further investigation of variants with this gene may be warranted.

Alcohol-related violence presenting to the emergency department : is ‘glassing’ the big issue?

Objective Describe the characteristics of patients presenting to Emergency Departments (EDs) within Queensland, Australia with injuries due to assault with a glass implement (‘glassing’) and to set this within the broader context of presentations due to alcohol-related violence. Methods Analysis of prospectively collected ED injury surveillance data collated by the Queensland Injury Surveillance Unit (QISU) between 1999 and 2011. Cases of injury due to alcohol-related violence were identified and analysed using coded fields supplemented with qualitative data contained within the injury description text. Descriptive statistics were used to assess the characteristics of injury presentations due to alcohol-related violence. Violence included interpersonal violence and aggression (verbal aggression and object violence). Results A total of 4629 cases were studied. The study population was predominantly male (72%) and aged 18 to 24 (36%), with males in this age group comprising more than a quarter of the study population (28%). Nine percent of alcohol-related assault injuries were a consequence of ‘glassing’. The home was the most common location for alcohol-related violence (31%) and alcohol-related ‘glassings’ (33%). Overall, the most common glass object involved was a bottle (75%), however, within licensed venues an even mix of a drinking glass (44%) and glass bottle (45%) were identified. Conclusions Contrary to public perception generated by media, ‘glassing’ incidents, particularly at licensed venues, constitute a relatively small proportion of all alcohol-related violence. The current study highlights the predominance of young men injured following alcohol-related violence, demonstrating a key focus area within the population for aiming prevention strategies.

Quality of life for older people in residential care is related to connectedness, willingness to enter care, and co-residents

Aim: To establish associations with quality of life (QOL) of older people in long-term residential care facilities in two New Zealand cities. Methods: The outcome measure of QOL was the Life Satisfaction Index. We used multiple linear regression to explore how broad categories of factors might contribute to QOL. Results: A total of 599 people (median age of 85 years; 74% women) participated. Response rates were 85% for facilities and 83% for residents. A resident's QOL was significantly related to the QOL of co-residents. QOL was higher for people who were more positive about entry to residential care, more physically able, and not depressed, and for those with more family and emotional support. Conclusion: Attending to the circumstances around entry to residential care may enhance QOL, as may promoting physical activity, treating depression and ensuring older people remain emotionally connected to their families. In choosing a facility, noting the QOL of co-residents is important.

Importance of sustainability-related cost components in highway infrastructure : perspective of stakeholders in Australia

Highway infrastructure development typically requires major capital input. Unless planned properly, such requirements can cause serious financial constraints for investors. The push for sustainability adds a new dimension to the complexity of evaluating highway projects. Finding environmentally and socially responsible solutions for highway construction will improve its potential for acceptance by the society and in many instances the infrastructure's life span. Even so, the prediction and determination of a project's long-term financial viability can be a precarious exercise. Existing studies in this area have not indicated details of how to identify and deal with costs incurred in pursuing sustainability measures in highway infrastructure. This paper provides insights into the major challenges of implementing sustainability in highway project development in terms of financial concerns and obligations. It discusses the results from recent research through a literature study and a questionnaire survey of key industry stakeholders involved in highway infrastructure development. The research identified critical cost components relating to sustainability measures based on perspectives of industry stakeholders. All stakeholders believe sustainability related costs are an integral part of the decision making. However, the importance rating of these costs is relative to each stakeholder's core business objectives. This will influence the way these cost components are dealt with during the evaluation of highway investment alternatives and financial implications. This research encourages positive thinking among the highway infrastructure practitioners about sustainability. It calls for the construction industry to maximise sustainability deliverables while ensuring financial viability over the life cycle of highway infrastructure projects.

Child-related factors that influence teacher-child relationships using an Australian national sample

This study assessed the extent to which child-related factors had an impact on teacher-child relationships in Australian childcare settings. Analyses used data from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC). The sample consisted of 1577 two to three year old children (M= 33.9 months, SD=2.93; 51.5% male). Two separate hierarchical multiple regression analyses were conducted to examine the relation between teachers’ perceptions of their relationships with children and (a) gender, (b), indigenous status, (c), language background other than English, (d), socio-economic position, (e) special health care needs, (f) expression and receptive language concerns, (g) psychosocial competence and problems and (h) temperament factors (approach, persistence and reactivity). Results indicated that special health care needs, receptive language concerns and all three temperament scales (approach, persistence and reactivity) significantly predicted conflict in teacher-child relationships. Close relationships were predicted by being female, indigenous status, higher socio-economic position, not having a special health care need and no expressive language concerns.

Age-related changes in cardiac adenosine receptor expression

Adenosine is an important cardioprotective agent that works via several adenosine receptor (ADOR) subtypes to regulate cardiovascular activity. It is well established that functional responses to adenosine decline with age. What is unclear, though, is whether these changes occur at the receptor, second messenger or translational level. In this study we determined the effect of age on cardiac adenosine receptor expression using the housekeeping gene 18S rRNA versus the adenosine A2B receptor gene as internal controls. Absolute quantification showed that no age-related changes occurred in the expression of 18S rRNA or adenosine A2B receptor internal control genes. Subsequently, relative analysis of the adenosine receptor subtypes using 18S rRNA found a significant age-related reduction in the expression of the adenosine A1 receptor (5.5-fold), with no changes in the expression of the adenosine A2A, A2B and A3 receptors. When using the expression of the adenosine A2B receptor as the internal control gene, a significant down regulation of both the adenosine A1 (5.4-fold) and A2A (2.2-fold) receptors with no change in the expression of adenosine A3 receptor was found. Therefore, the high level of expression of the 18S rRNA housekeeping gene was found to mask a significant change in expression of the adenosine A2A receptor with age. Ultimately, these findings show an age-related reduction in adenosine A1 and A2A receptor expression in rat heart.

The role of adenosine-related genes variants in susceptibility to essential hypertension

OBJECTIVE: To test markers within adenosine-related genes: A1 and A2a receptors (ADORA1, ADORA2a) and adenosine deaminase (ADA) for potential involvement in essential hypertension (EH). DESIGN: Case-control association study investigating gene variants for the ADORA1, ADORA2a and ADA genes. PARTICIPANTS: The study used a cohort of 249 unrelated hypertensive individuals who were diagnosed with hypertension, and an age, sex and ethnically matched group of 249 normotensive controls. RESULTS: The association analysis indicated that both allele and genotype frequencies did not differ significantly between the case and control groups (P > 0.05) for any of the markers tested. CONCLUSION: The adenosine-related gene variants do not appear to alter susceptibility to the disease in this group of essential hypertensives. However, involvement of these genes and the adenosine system cannot be conclusively excluded from essential hypertension pathogenesis as other gene variants may still be involved.

Predictors of physical and mental health-related quality of life outcomes among myocardial infarction patients

Background Health-related quality of life (HRQoL) is an important outcome for patients diagnosed with coronary heart disease. This report describes predictors of physical and mental HRQoL at six months post-hospitalisation for myocardial infarction. Methods Participants were myocardial infarction patients (n=430) admitted to two tertiary referral centres in Brisbane, Australia who completed a six month coronary heart disease secondary prevention trial (ProActive Heart). Outcome variables were HRQoL (Short Form-36) at six months, including a physical and mental summary score. Baseline predictors included demographics and clinical variables, health behaviours, and psychosocial variables. Stepwise forward multiple linear regression analyses were used to identify significant independent predictors of six month HRQoL. Results Physical HRQoL was lower in participants who: were older (p<0.001); were unemployed (p=0.03); had lower baseline physical and mental HRQoL scores (p<0.001); had lower confidence levels in meeting sufficient physical activity recommendations (p<0.001); had no intention to be physically active in the next six months (p<0.001); and were more sedentary (p=0.001). Mental HRQoL was lower in participants who: were younger (p=0.01); had lower baseline mental HRQoL (p<0.001); were more sedentary (p=0.01) were depressed (p<0.001); and had lower social support (p=0.001). Conclusions This study has clinical implications as identification of indicators of lower physical and mental HRQoL outcomes for myocardial infarction patients allows for targeted counselling or coronary heart disease secondary prevention efforts. Trial registration Australian Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, CTRN12607000595415. Keywords: Myocardial infarction; Secondary prevention; Cardiac rehabilitation; Telephone-delivered; Health-related quality of life; Health coaching; Tele-health

Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer

We assessed whether alternative transcripts (using KLK2, KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance

Genetic variation in cytokine-related genes and migraine susceptibility

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (LTA), and lymphotoxin β (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNFα contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.

Beyond normal competencies : understanding organisation designs to develop and sustain IT-related capabilities

It is apparent that IT resources are important for organisations. It is also clear that organisations unique competencies, their IT-related capabilities, leverage the IT resources uniquely to create and sustain competitive advantage. However, IT resources are dynamic, and evolve at an exponential rate. This means that organisations will need to sustain their competencies to leverage opportunities offered by new IT resources. Research on ways to sustain IT-related capabilities is limited and a deeper understanding of this situation is important. Amongst other factors, a possible reason for this lack of progress in this area could be due to the lack of validated measurement items of the theoretical constructs to conduct such studies. We suggest an environment in which organisations could build new and sustain their existing IT-related capabilities. We then report on the development of valid and reliable measures for this environment. The validated measures would be useful in extending our understanding on how firms could sustain their IT-related capabilities. This effort will provide a deeper understanding of how firms can secure sustainable IT-related business value from their acquired IT resources.

Natural, engineered and synthetic inhibitors of kallikrein-related peptidases

There is a rapidly growing appreciation of the important physiological roles played by kallikreins and kallikrein-related peptidases (KLKs). Recent studies have revealed that these enzymes control key events in processes as diverse as inflammation and skin desquamation. Accordingly, there is considerable interest in developing tools to further dissect kallikrein activity, and a burgeoning effort aimed at producing lead inhibitors for therapeutic development. Indeed, several candidate inhibitors are already in clinical trials. This chapter surveys the naturally occurring kallikrein inhibitors, together with strategies for employing these molecules as bioscaffolds, as well as current progress in the development of small-molecule kallikrein inhibitors.

Vitamin D related behaviours among pregnant women in Australia

Vitamin D deficiency is common in pregnancy, and it has numerous health implications in both the mother and the baby. Vitamin D is made by skin from sun exposure or ingested from the diet. As there is a high prevalence of vitamin D deficiency in pregnant women, it is important to understand how pregnant women behave in relation to sun exposure and for vitamin D intake. This thesis aimed to answer this question. Through this study, public health and other intervention strategies to facilitate appropriate sun exposure and vitamin D intake will be developed.

Drinking and riding: is subjective workload related to performance?

Introduction: Within the context of road safety it is important that workload (the portion of a driver’s resources expended to perform a task) remains at a manageable level, preventing overloading and consequently performance decrements. Motorcyclists are over represented in crash statistics where the vehicle operator has a positive, low blood alcohol concentration (BAC) (e.g., 0.05%). The NASA task load index (NASA-TLX) comprises sub-scales that purportedly assess different aspects of subjective workload. It was hypothesized that, compared to a zero BAC condition, low BACs would be associated with increases in workload ratings, and decrements in riding performance. Method: Forty participants (20 novice, 20 experienced) completed simulated motorcycle rides in urban and rural scenarios under low dose BAC conditions (0.00%, 0.02%, 0.05% BAC), while completing a safety relevant peripheral detection task (PDT). Six sub-scales of the NASA-TLX were completed after each ride. Riding performance was assessed using standard deviation of lateral position (SDLP). Hazard perception was assessed by response time to the PDT. Results: Riding performance and hazard perception were affected by alcohol. There was a significant increase in SDLP in the urban scenario and of PDT reaction time in the rural scenario under 0.05% BAC compared to 0.00% BAC. Overall NASA-TLX score increased at 0.02% and 0.05% BAC in the urban environment only, with a trend for novices to rate workload higher than experienced riders. There was a significant main effect of sub-scale on workload ratings in both the urban and rural scenarios. Discussion: 0.05% BAC was associated with decrements in riding performance in the urban environment, decrements in hazard perception in the rural environment, and increases in overall ratings of subjective workload in the urban environment. The workload sub-scales of the NASA-TLX appear to be measuring distinct aspects of motorcycle riding-related workload. Issues of workload and alcohol impaired riding performance are discussed.

Self-management of chemotherapy-related nausea and vomiting : a cross-sectional survey of Chinese cancer patients

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV) remain prevalent among cancer patients despite pharmacological advances in CINV therapy. Patients can initiate nonpharmacologic strategies, which potentially play an important role as adjuncts to pharmacological agents in alleviating CINV. Some studies have explored nausea and vomiting self-management (NVSM) behaviors among patients in Western settings; however, little is known about the NVSM behaviors of patients in China. OBJECTIVES This study examines NVSM behaviors of Chinese cancer patients. METHODS A cross-sectional survey was conducted in a specialist cancer hospital in southeast China. RESULTS A sample of 255 cancer patients was recruited. A mean of 8.56 (±3.15) NVSM behaviors was reported. Most NVSM behaviors were rated as moderately effective and were implemented with moderate self-efficacy. Higher distress levels, better functional status, previous similar symptom experiences, receiving chemotherapy as an inpatient, and greater support from multiple levels were related to greater engagement in NVSM; higher self-efficacy levels pertaining to NVSM behaviors were associated with reports of more relief from specific NVSM behaviors. CONCLUSIONS A range of NVSM strategies was initiated by Chinese cancer patients and provided some relief. A range of individual, health status, and environmental factors influenced engagement with and relief from NVSM behaviors. IMPLICATIONS FOR PRACTICE To enhance Chinese patients' NVSM, patients should be supported to engage in behaviors including taking antiemetics, modifying their diet, using psychological strategies, and creating a pleasant environment. The findings highlight the importance of enhancing patients' self-efficacy in NVSM, alleviating symptom distress, and improving social support to achieve better outcomes.