Postoperative pain relief using intermittent intrapleural analgesia following thoracoscopic anterior correction for progressive adolescent idiopathic scoliosis

Background Thoracoscopic anterior scoliosis instrumentation is a safe and viable surgical option for corrective fusion of progressive adolescent idiopathic scoliosis (AIS) and has been performed at our centre on 205 patients since 2000. However, there is a paucity of literature reporting on or examining optimum methods of analgesia following this type of surgery. A retrospective study was designed to present the authors’ technique for delivering intermittent local anaesthetic boluses via an intrapleural catheter following thoracoscopic scoliosis surgery; report the pain levels that may be expected and any adverse effects associated with the use of intrapleural analgesia, as part of a combined postoperative analgesia regime. Methods Records for 32 patients who underwent thoracoscopic anterior correction for AIS were reviewed. All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Patient’s perceptions of their pain control was measured using the visual analogue pain scale scores which were recorded before and after local anaesthetic administration and the quantity and time of day that any other analgesia was taken, were also recorded. Results 28 female and four male patients (mean age 14.5 ± 1.5 years) had a total of 230 boluses of local anaesthetic administered in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p < 0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal due to leakage; there were no other associated complications with the intermittent intrapleural analgesia method. Conclusions Local anaesthetic administration via an intrapleural catheter is a safe and effective method of analgesia following thoracoscopic anterior scoliosis correction. Post-operative pain following anterior thoracic scoliosis surgery can be reduced to ‘mild’ levels by combined analgesia regimes. Keywords: Adolescent idiopathic scoliosis; Thoracoscopic anterior spinal fusion; Anterior fusion; Intrapleural analgesia; Endoscopic anterior surgery; Pain relief; Scoliosis surgery

Outcomes of an early feeding practices intervention to prevent childhood obesity

Objective Use a randomised controlled trial (RCT) to evaluate outcomes of a universal intervention to promote protective feeding practices, which commenced in infancy and aimed to prevent childhood obesity Subjects and Methods The NOURISH RCT enrolled 698 first-time mothers (mean age 30.1 years, SD=5.3) with healthy term infants (51% female) aged 4.3 (SD=1.0) months at baseline. Mothers were randomly allocated to self-directed access to usual care or to attend two 6-session interactive group education modules that provided anticipatory guidance on early feeding practices. Outcomes were assessed six months after completion of the second information module, 20 months from baseline and when the children were two years old. Maternal feeding practices were self-reported using validated questionnaires and study-developed items. Study-measured child height and weight were used to calculate BMI Z-score. Results Retention at follow-up was 78%. Mothers in the intervention group reported using responsive feeding more frequently on 6/9 subscales and 8/8 items (Ps ≤.03) and overall less ‘controlling feeding practices’ (P<.001). They also more frequently used feeding practices (3/4 items; Ps <.01) likely to enhance food acceptance. No statistically significant differences were noted in anthropometric outcomes (BMI Z-score: P=.11), nor in prevalence of overweight/obesity (control 17.9% vs. intervention 13.8%, P=.23). Conclusions Evaluation of NOURISH at child age two years found that anticipatory guidance on complementary feeding, tailored to developmental stage, increased use by first-time mothers of 'protective' feeding practices that potentially support the development of healthy eating and growth patterns in young children.

Are we missing opportunities? Understanding health behaviours associated with overweight in pregnancy

While maternal obesity, excess pregnancy weight gain and lifestyle behaviours are associated with future overweight for both mothers and babies, there is limited research on how best to intervene. An evidence base that identifies behavioural influences is crucial to the development of effective interventions. This thesis aims to gain an understanding of maternal behavioural outcomes of healthy eating, physical activity and gestational weight gain (GWG), the psychosocial influences on these and to examine differences according to pre-pregnancy weight status. The New Beginnings Healthy Mothers and Babies Study was a prospective observational study using the PRECEDE-PROCEED model of health promotion planning as a framework. A consecutive sample of 715 women was recruited. Height and weight were measured and women completed questionnaires at approximately 16 and 36 weeks gestation. This thesis presents three chapters of original research across four study domains. While healthy eating was widely regarded as important during pregnancy and had become more so, there was more variability in attitudes towards physical activity. Ninety-two percent of participants achieved the maximum knowledge score relating to the influence of nutrition on pregnancy. However, 8% and 36% respectively knew how many serves of fruit and vegetables should be consumed daily. Six percent of participants met the recommendations for fruit consumption, 4% achieved the recommended vegetable intake and 44% achieved sufficient physical activity. There were few differences between healthy and overweight women for measures of physical activity and healthy eating. Many predisposing, reinforcing and enabling factors with a positive influence on health behaviours were lower in women commencing pregnancy overweight and those factors with a negative influence on health behaviours were higher when compared to healthy weight women. Some of these antecedents to health behaviours that were different according to prepregnancy weight status were associated with diet quality and physical activity. While self efficacy was consistently associated with diet quality and physical activity for both weight groups, other associations between specific predisposing, reinforcing and enabling factors differed with behaviour and weight status group. These results highlight the complexity of supporting behaviour change in a one-size-fits-all approach. Sixty-four percent of participants gained weight outside of recommendations. Compared to healthy weight women, those women who were already overweight at the beginning of pregnancy were more likely to gain too much weight (30% vs 56%, p<0.001). Only 35% of participants reported their correct recommended weight gain. Excess GWG was associated with few predisposing factors, however, these were not consistent between prepregnancy weight status groups. Less than 50% of women reported sometimes/usually/always receiving advice from health professionals relating to healthy eating, physical activity or GWG. These results indicate that there are opportunities to improve the advice and support provided by health care professionals in the antenatal period. Evidence from this PhD research suggests that there is a need for effective prevention and management of excess weight in pregnancy. Effective management of this problem is likely to require a multidisciplinary approach with multi-level strategies. Importantly, the strategies may need to be tailored according to pre-pregnancy weight status. Collectively, the evidence derived from this thesis suggests that opportunities to support healthy lifestyles and prevent future overweight are being missed during pregnancy.

The HealthyTexts study : A randomized controlled trial to improve skin cancer prevention behaviors among young people

Several randomized trials have found behavior change programs delivered via text messaging to be efficacious to improve preventive health behaviors such as physical activity and stopping smoking; however few have assessed its value in skin cancer prevention or early detection. The HealthyTexts study enrolled 678 participants 18–42 years, and assigned them to receive 21 text messages about skin cancer prevention, skin self-examination or physical activity(attention control) over the course of one year. Baseline data have been collected and outcomes will be assessed at three months and twelve months post intervention. The trial aims to increase the mean overall sun protection habits index score from 2.3 to 2.7 with a standard deviation of 0.5 (effect size of 0.5) and the proportion of people who conduct a whole-body skin self-examination by an absolute 10%. This paper describes the study design and participants' baseline characteristics. In addition, participants' goals for their health, and strategies they apply to achieve those goals are summarized.

The effect of exercise training on sleep quality in heart failure

Background: Heart failure is a serious condition estimated to affect 1.5-2.0% of the Australian population with a point prevalence of approximately 1% in people aged 50-59 years, 10% in people aged 65 years or more and over 50% in people aged 85 years or over (National Heart Foundation of Australian and the Cardiac Society of Australia and New Zealand, 2006). Sleep disturbances are a common complaint of persons with heart failure. Disturbances of sleep can worsen heart failure symptoms, impair independence, reduce quality of life and lead to increased health care utilisation in patients with heart failure. Previous studies have identified exercise as a possible treatment for poor sleep in patients without cardiac disease however there is limited evidence of the effect of this form of treatment in heart failure. Aim: The primary objective of this study was to examine the effect of a supervised, hospital-based exercise training programme on subjective sleep quality in heart failure patients. Secondary objectives were to examine the association between changes in sleep quality and changes in depression, exercise performance and body mass index. Methods: The sample for the study was recruited from metropolitan and regional heart failure services across Brisbane, Queensland. Patients with a recent heart failure related hospital admission who met study inclusion criteria were recruited. Participants were screened by specialist heart failure exercise staff at each site to ensure exercise safety prior to study enrolment. Demographic data, medical history, medications, Pittsburgh Sleep Quality Index score, Geriatric Depression Score, exercise performance (six minute walk test), weight and height were collected at Baseline. Pittsburgh Sleep Quality Index score, Geriatric Depression Score, exercise performance and weight were repeated at 3 months. One hundred and six patients admitted to hospital with heart failure were randomly allocated to a 3-month disease-based management programme of education and self-management support including standard exercise advice (Control) or to the same disease management programme as the Control group with the addition of a tailored physical activity program (Intervention). The intervention consisted of 1 hour of aerobic and resistance exercise twice a week. Programs were designed and supervised by an exercise specialist. The main outcome measure was achievement of a clinically significant change (.3 points) in global Pittsburgh Sleep Quality score. Results: Intervention group participants reported significantly greater clinical improvement in global sleep quality than Control (p=0.016). These patients also exhibited significant improvements in component sleep disturbance (p=0.004), component sleep quality (p=0.015) and global sleep quality (p=0.032) after 3 months of supervised exercise intervention. Improvements in sleep quality correlated with improvements in depression (p<0.001) and six minute walk distance (p=0.04). When study results were examined categorically, with subjects classified as either "poor" or "good" sleepers, subjects in the Control group were significantly more likely to report "poor" sleep at 3 months (p=0.039) while Intervention participants were likely to report "good" sleep at this time (p=0.08). Conclusion: Three months of supervised, hospital based, aerobic and resistance exercise training improved subjective sleep quality in patients with heart failure. This is the first randomised controlled trial to examine the role of aerobic and resistance exercise training in the improvement of sleep quality for patients with this disease. While this study establishes exercise as a therapy for poor sleep quality, further research is needed to investigate the effect of exercise training on objective parameters of sleep in this population.

Mortality and cost outcomes of elderly trauma patients admitted to intensive care and the general wards of an Australian tertiary referral hospital

Mortality and cost outcomes of elderly intensive care unit (ICU) trauma patients were characterised in a retrospective cohort study from an Australian tertiary ICU. Trauma patients admitted between January 2000 and December 2005 were grouped into three major age categories: aged ≥65 years admitted into ICU (n=272); aged ≥65 years admitted into general ward (n=610) and aged <65 years admitted into ICU (n=1617). Hospital mortality predictors were characterised as odds ratios (OR) using logistic regression. The impact of predictor variables on (log) total hospital-stay costs was determined using least squares regression. An alternate treatment-effects regression model estimated the mortality cost-effect as an endogenous variable. Mortality predictors (P ≤0.0001, comparator: ICU ≥65 years, ventilated) were: ICU <65 not-ventilated (OR 0.014); ICU <65 ventilated (OR 0.090); ICU age ≥65 not-ventilated (OR 0.061) and ward ≥65 (OR 0.086); increasing injury severity score and increased Charlson comorbidity index of 1 and 2, compared with zero (OR 2.21 [1.40 to 3.48] and OR 2.57 [1.45 to 4.55]). The raw mean daily ICU and hospital costs in A$ 2005 (US$) for age <65 and ≥65 to ICU, and ≥65 to the ward were; for year 2000: ICU, $2717 (1462) and $2777 (1494); hospital, $1837 (988) and $1590 (855); ward $933 (502); for year 2005: ICU, $3202 (2393) and $3086 (2307); hospital, $1938 (1449) and $1914 (1431); ward $1180 (882). Cost increments were predicted by age ≥65 and ICU admission, increasing injury severity score, mechanical ventilation, Charlson comorbidity index increments and hospital survival. Mortalitycost-effect was estimated at -63% by least squares regression and -82% by treatment-effects regression model. Patient demographic factors, injury severity and its consequences predict both cost and survival in trauma. The cost mortality effect was biased upwards by conventional least squares regression estimation.

Time to change consumer involvement in nursing research

The experiences of people affected by cancer are at the very heart of nursing research efforts. Because much of our work is focused on understanding how to improve experiences and outcomes for people with cancer, it is easy for us to believe that our research is inherently "person centered" and thus collaborative. Let's reflect on what truly collaborative approaches to cancer nursing research could be like, and how we measure up to such goals. Collaboration between people affected by cancer (consumers) and nurses in research is much more than providing a voice for individuals as participants in a research study. Today, research governing bodies in many countries require us to seek a different kind of consumer participation, where consumers and researchers work in partnership with one another to shape decisions about research priorities, policies, and practices.1 Most granting bodies now require explanations of how consumer and community participation will occur within a study. Ethical imperatives and the concept of patient advocacy also require that we give more considered attention to what is meant by consumer involvement.2 Consumers provide perspective on what will be relevant, acceptable, feasible, and sensitive research, having lived the experience of cancer. As a result, they offer practical insights that can ensure the successful conduct and better outcomes from research. Some granting bodies now even allocate a proportion of final score or assign a "public value" weighting for a grant, to recognize the importance of consumer involvement and reflect the quality of patient involvement in all stages of the research process.3

A micro-level indexing model for the assessment of sustainable urban ecosystems

During the last several decades, the quality of natural resources and their services have been exposed to significant degradation from increased urban populations combined with the sprawl of settlements, development of transportation networks and industrial activities (Dorsey, 2003; Pauleit et al., 2005). As a result of this environmental degradation, a sustainable framework for urban development is required to provide the resilience of natural resources and ecosystems. Sustainable urban development refers to the management of cities with adequate infrastructure to support the needs of its population for the present and future generations as well as maintain the sustainability of its ecosystems (UNEP/IETC, 2002; Yigitcanlar, 2010). One of the important strategic approaches for planning sustainable cities is „ecological planning‟. Ecological planning is a multi-dimensional concept that aims to preserve biodiversity richness and ecosystem productivity through the sustainable management of natural resources (Barnes et al., 2005). As stated by Baldwin (1985, p.4), ecological planning is the initiation and operation of activities to direct and control the acquisition, transformation, disruption and disposal of resources in a manner capable of sustaining human activities with a minimum disruption of ecosystem processes. Therefore, ecological planning is a powerful method for creating sustainable urban ecosystems. In order to explore the city as an ecosystem and investigate the interaction between the urban ecosystem and human activities, a holistic urban ecosystem sustainability assessment approach is required. Urban ecosystem sustainability assessment serves as a tool that helps policy and decision-makers in improving their actions towards sustainable urban development. There are several methods used in urban ecosystem sustainability assessment among which sustainability indicators and composite indices are the most commonly used tools for assessing the progress towards sustainable land use and urban management. Currently, a variety of composite indices are available to measure the sustainability at the local, national and international levels. However, the main conclusion drawn from the literature review is that they are too broad to be applied to assess local and micro level sustainability and no benchmark value for most of the indicators exists due to limited data availability and non-comparable data across countries. Mayer (2008, p. 280) advocates that by stating "as different as the indices may seem, many of them incorporate the same underlying data because of the small number of available sustainability datasets". Mori and Christodoulou (2011) also argue that this relative evaluation and comparison brings along biased assessments, as data only exists for some entities, which also means excluding many nations from evaluation and comparison. Thus, there is a need for developing an accurate and comprehensive micro-level urban ecosystem sustainability assessment method. In order to develop such a model, it is practical to adopt an approach that uses a method to utilise indicators for collecting data, designate certain threshold values or ranges, perform a comparative sustainability assessment via indices at the micro-level, and aggregate these assessment findings to the local level. Hereby, through this approach and model, it is possible to produce sufficient and reliable data to enable comparison at the local level, and provide useful results to inform the local planning, conservation and development decision-making process to secure sustainable ecosystems and urban futures. To advance research in this area, this study investigated the environmental impacts of an existing urban context by using a composite index with an aim to identify the interaction between urban ecosystems and human activities in the context of environmental sustainability. In this respect, this study developed a new comprehensive urban ecosystem sustainability assessment tool entitled the „Micro-level Urban-ecosystem Sustainability IndeX‟ (MUSIX). The MUSIX model is an indicator-based indexing model that investigates the factors affecting urban sustainability in a local context. The model outputs provide local and micro-level sustainability reporting guidance to help policy-making concerning environmental issues. A multi-method research approach, which is based on both quantitative analysis and qualitative analysis, was employed in the construction of the MUSIX model. First, a qualitative research was conducted through an interpretive and critical literature review in developing a theoretical framework and indicator selection. Afterwards, a quantitative research was conducted through statistical and spatial analyses in data collection, processing and model application. The MUSIX model was tested in four pilot study sites selected from the Gold Coast City, Queensland, Australia. The model results detected the sustainability performance of current urban settings referring to six main issues of urban development: (1) hydrology, (2) ecology, (3) pollution, (4) location, (5) design, and; (6) efficiency. For each category, a set of core indicators was assigned which are intended to: (1) benchmark the current situation, strengths and weaknesses, (2) evaluate the efficiency of implemented plans, and; (3) measure the progress towards sustainable development. While the indicator set of the model provided specific information about the environmental impacts in the area at the parcel scale, the composite index score provided general information about the sustainability of the area at the neighbourhood scale. Finally, in light of the model findings, integrated ecological planning strategies were developed to guide the preparation and assessment of development and local area plans in conjunction with the Gold Coast Planning Scheme, which establishes regulatory provisions to achieve ecological sustainability through the formulation of place codes, development codes, constraint codes and other assessment criteria that provide guidance for best practice development solutions. These relevant strategies can be summarised as follows: • Establishing hydrological conservation through sustainable stormwater management in order to preserve the Earth’s water cycle and aquatic ecosystems; • Providing ecological conservation through sustainable ecosystem management in order to protect biological diversity and maintain the integrity of natural ecosystems; • Improving environmental quality through developing pollution prevention regulations and policies in order to promote high quality water resources, clean air and enhanced ecosystem health; • Creating sustainable mobility and accessibility through designing better local services and walkable neighbourhoods in order to promote safe environments and healthy communities; • Sustainable design of urban environment through climate responsive design in order to increase the efficient use of solar energy to provide thermal comfort, and; • Use of renewable resources through creating efficient communities in order to provide long-term management of natural resources for the sustainability of future generations.

Is intermittent intrapleural analgesia safe and effective following thoracoscopic anterior scoliosis correction surgery?

Introduction: Thoracoscopic anterior instrumented fusion (TASF) is a safe and viable surgical option for corrective stabilisation of progressive adolescent idiopathic scoliosis (AIS) [1-2]. However, there is a paucity of literature examining optimum methods of analgesia following this type of surgery. The aim of this study was to identify; if local anaesthetic bolus via an intrapleural catheter provides effective analgesia following thoracoscopic scoliosis correction; what pain levels may be expected; and any adverse effects associated with the use of intermittent intrapleural analgesia at our centre. Methods: A subset of the most recent 80 patients from a large single centre consecutive series of 201 patients (April 2000 to present) who had undergone TASF had their medical records reviewed. 32 patients met the inclusion criteria for the analysis (i.e. pain scores must have been recorded within the hour prior and within two hours following an intrapleural bolus being given). All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia as required. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Visual analogue pain scale scores were recorded before and after the bolus of local anaesthetic and the quantity and time of day that any other analgesia was taken, were also recorded. Results and Discussion: 28 female and four male patients (mean age 14.5 ± 1.5 years) had a total of 230 boluses of local anaesthetic administered intrapleurally, directly onto the spine, in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p<0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal at 26 hours postop due to leakage; there were no other associated complications with the intermittent intrapleural analgesia method. Post-operative pain following anterior scoliosis correction was decreased significantly with the administration of regular local anaesthetic boluses and can be reduced to ‘mild’ levels by combined analgesia regimes. The intermittent intrapleural analgesia method was not associated with any adverse events or complications in the full cohort of 201 patients.

Reducing the Risk of Alcohol and Other Drugs in Construction : An Australian Assessment

There is increasing concern about the impact of employees’ alcohol and other drug (AOD) consumption on workplace safety, particularly within the construction industry. No known study has scientifically evaluated the relationship between the use of drugs and alcohol and safety impacts in construction, and there has been only limited adoption of nationally coordinated strategies, supported by employers and employees to render it socially unacceptable to arrive at a construction workplace with impaired judgment from AODs. This research aims to scientifically evaluate the use of AODs within the Australian construction industry in order to reduce the potential resulting safety and performance impacts and engender a cultural change in the workforce. Using the Alcohol Use Disorders Identification Test (AUDIT), the study will adopt both quantitative and qualitative methods to evaluate the extent of general AOD use in the industry. Results indicate that a proportion of the construction sector may be at risk of hazardous alcohol consumption. A total of 286 respondents (58%) scored above the cut-off score for risky alcohol use with 43 respondents (15%) scoring in the significantly ‘at risk’ category. Other drug use was also identified as a major issue that must be addressed. Results support the need for evidence-based, preventative educational initiatives that are tailored specifically to the construction industry.

Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of Liu Wei Di Huang Wan detected by UPLC-HDMS

The promise of metabonomics, a new "omics" technique, to validate Chinese medicines and the compatibility of Chinese formulas has been appreciated. The present study was undertaken to explore the excretion pattern of low molecular mass metabolites in the male Wistar-derived rat model of kidney yin deficiency induced with thyroxine and reserpine as well as the therapeutic effect of Liu Wei Di Huang Wan (LW) and its separated prescriptions, a classic traditional Chinese medicine formula for treating kidney yin deficiency in China. The study utilized ultra-performance liquid chromatography/electrospray ionization synapt high definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) in both negative and positive electrospray ionization (ESI). At the same time, blood biochemistry was examined to identify specific changes in the kidney yin deficiency. Distinct changes in the pattern of metabolites, as a result of daily administration of thyroxine and reserpine, were observed by UPLC-HDMS combined with a principal component analysis (PCA). The changes in metabolic profiling were restored to their baseline values after treatment with LW according to the PCA score plots. Altogether, the current metabonomic approach based on UPLC-HDMS and orthogonal projection to latent structures discriminate analysis (OPLS-DA) indicated 20 ions (14 in the negative mode, 8 in the positive mode, and 2 in both) as "differentiating metabolites".

Functional analysis of missense variants in the TRESK (KCNK18) K+ channel

A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.

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.

The human μ-opioid receptor gene polymorphism (A118G) is associated with head pain severity in a clinical cohort of female migraine with aura patients

Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatments work with differing efficacies in migraineurs. The opioid system plays an important role in diverse biological functions including analgesia, drug response and pain reduction. The A118G single nucleotide polymorphism (SNP) in exon 1 of the μ-opioid receptor gene (OPRM1) has been associated with elevated pain responses and decreased pain threshold in a variety of populations. The aim of the current preliminary study was to test whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. This was a preliminary study to determine whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. A total of 153 chronic migraine with aura sufferers were assessed for migraine head pain using the Migraine Disability Assessment Score instrument and classified into high and low pain severity groups. DNA was extracted and genotypes obtained for the A118G SNP. Logistic regression analysis adjusting for age effects showed the A118G SNP of the OPRM1 gene to be significantly associated with migraine pain severity in the test population (P = 0.0037). In particular, G118 allele carriers were more likely to be high pain sufferers compared to homozygous carriers of the A118 allele (OR = 3.125, 95 % CI = 1.41, 6.93, P = 0.0037). These findings suggest that A118G genotypes of the OPRM1 gene may influence migraine-associated head pain in females. Further investigations are required to fully understand the effect of this gene variant on migraine head pain including studies in males and in different migraine subtypes, as well as in response to head pain medication.

Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients

Recent association studies in multiple sclerosis (MS) have identified and replicated several single nucleotide polymorphism (SNP) susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13–14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.