A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

Many primary immunodeficiency disorders of differing etiologies have been well characterized, and much understanding of immunological processes has been gained by investigating the mechanisms of disease. Here, we have used a whole-genome approach, employing single-nucleotide polymorphism and gene expression microarrays, to provide insight into the molecular etiology of a novel immunodeficiency disorder. Using DNA copy number profiling, we define a hyperploid region on 14q11.2 in the immunodeficiency case associated with the interleukin (IL)-25 locus. This alteration was associated with significantly heightened expression of IL25 following T-cell activation. An associated dominant type 2 helper T cell bias in the immunodeficiency case provides a mechanistic explanation for recurrence of infections by pathogens met by Th1-driven responses. Furthermore, this highlights the capacity of IL25 to alter normal human immune responses.

Prevalence and characteristics of Indigenous drink-driving convictions in Queensland, Australia

Alcohol-involved accidents are one of the leading contributors towards high injury rates among Indigenous Australians. However, there is limited information available to inform existing policies to change current rates. The study aims to provide information about the prevalence and the characteristics of such behaviour. Drink driving convictions from 2006-2010 were extracted from the Queensland Department of Justice and Attorney General database. Convictions were regrouped by gender, age, Accessibility/Remoteness Index of Australia classification (using court location) and sentence severity. A number of cross tabulations were carried out to identify relationships between variables. Standardised adjusted residuals were calculated for each cell in order to determine cell differences that contributed to the chi-square test results. Analysis revealed there were 9,323 convictions, of which the majority were for offences by males (77.5%). In relation to age, 52.6% of the convictions were of persons under 25 years of age. Age was significantly different across the five regions for males only (χ2=90.8, p<0.001), with a larger number of convictions in the ‘very remote’ region of persons over 40+ years of age. Increased remoteness was linked with high range BAC convictions for both males (χ2=168.4, p<0.001) and females (χ2=22.5, p=0.004). Monetary penalties were the primary sentence received for both males and females in all regions. The findings identify the Indigenous drink driving conviction rate to be 6 times that of the general Queensland rate and indicate that a multipronged approach is needed, with tailored strategies for remote offenders, young adults and offenders with alcohol misuse and dependency issues. Further attention is warranted in this area of road safety.

Prevalence and predictors of refractive error in a genetically isolated population : the Norfolk Island Eye Study

BACKGROUND: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. DESIGN: Population-based study on Norfolk Island, South Pacific. PARTICIPANTS: All permanent residents on Norfolk Island aged ≥ 15 years were invited to participate. METHODS: Patients underwent non-cycloplegic autorefraction, slit-lamp biomicroscope examination and biometry assessment. Only phakic eyes were analysed. MAIN OUTCOME MEASURES: Prevalence and multivariate associations of refractive error and myopia. RESULTS: There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7; range 15-81). Three hundred and seventy-six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥ -1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). CONCLUSIONS: The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.

Prevalence and correlates of sleep disturbance in post-menopausal Australian women : the Healthy Aging of Women (HOW) study

Background: Sleep disturbance in midlife women has been studied extensively, although less is known about sleep after menopause. This study examined the relative impact of socio-demographics, modifiable lifestyle factors, and health status on sleep disturbance in post-menopausal women from Queensland, Australia. Methods: The longitudinal Healthy Aging of Women (HOW) study examines health-related quality of life (HRQOL measured by SF-12©), chronic illness, modifiable lifestyle factors such as physical activity, alcohol consumption, smoking, and sleep disturbance (General Sleep Disturbance Scale, GSDS ≥ 43 represent poor sleep) in midlife and older women from low and high socio-economic, rural and urban areas of South-East Queensland, Australia. This paper presents cross-sectional data from the 322 women, aged 60-70 years, participating in the HOW study in 2011. Results: For women in this study, sleep disturbance was relatively common, with 23% (n = 83) reporting poor sleeping (GSDS ≥ 43). Sleep disturbance scores were strongly correlated with being unemployed or on a disability support pension (β = 18.69, P < 0.01), sedentary lifestyle (β = 23.84, P < 0.01), and lower mental (β = -0.60, P <0.01) and physical health-related quality of life scores (β = -0.32, P = 0.01), and these variables explained almost one third of variance in sleep disturbance scores (ηρ² = 29%). Conclusions: Multivariable analysis revealed that sleep disturbance was correlated with physical and mental health-related quality of life, disability, and sedentary lifestyle, but not other lifestyle and socio-demographic characteristics. It may be however, that modifiable lifestyle factors may indirectly impact on sleep by influencing health status.

The methylentetrahydrofolate reductase gene variant (C677T) as a risk factor for essential hypertension in Caucasians

Essential hypertension (EH) is a common, multifactorial disorder likely to be influenced by multiple genes of modest effect. The methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation is functionally important, being strongly associated with reduced enzyme activity and increased plasma levels of homocysteine. Mild hyperhomocysteinemia is a known risk factor for cardiovascular disease (CVD) and hypothesised also to be involved in hypertension pathophysiology. The present study was performed to determine the prevalence of the 677T mutation in Australian Caucasian patients diagnosed with EH and to test whether the C677T variant is associated with the disorder. A case-control cohort, consisting of 250 EH patients and 250 age, sex and racially matched normotensive controls, were used for the association study. Comparison of C677T allele frequencies revealed a higher proportion of the mutant allele (T) in the EH group (40%) compared to unaffected controls (34%) (p=0.07). Furthermore, genotypic results indicated that the prevalence of the homozygous mutant genotype (T/T) in the affected group was higher than that of controls (14%:10%) (p=0.17). Interestingly, conditional logistic regression showed that the MTHFR C677T mutation conferred a mild, yet significant increase in risk of essential hypertension after adjusting for body mass index (odds ratio=1.57, 95% confidence interval: 1.04-2.37, p=0.03). These findings require further investigation in large independent samples, but suggest that essential hypertension, like CVD, may be mildly influenced by the MTHFR C677T variant.

Evidence for an X-linked genetic component in familial typical migraine

Migraine is a common complex disorder that shows strong familial aggregation. There is a general increased prevalence of migraine in females compared with males, with recent studies indicating that migraine affects 18% of females compared with 6% of males. This preponderance of females among migraine sufferers coupled with evidence of an increased risk of migraine in first degree relatives of male probands but not in relatives of female probands suggests the possibility of an X-linked dominant gene. We report here the localization of a typical migraine susceptibility locus to the X chromosome. Of three large multigenerational migraine pedigrees two families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigrees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the localization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male probands and may be involved in the increased female prevalence of this disorder.

The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

Prevalence of chronic ocular diseases in a genetic isolate : the Norfolk Island Eye Study (NIES)

Purpose: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18 th century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island. Methods: All permanent residents of Norfolk Island aged ≥ 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy. Results: We recruited 781 people aged ≥ 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged ≥ 40 was 1.5%. Blindness was more common in females (P=0.049) and less common in people with Pitcairn Island ancestry (P<0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P<0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry. Conclusions: The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.

Prevalence, trends and associated socio-economic factors of obesity in South Asia

Aim Worldwide obesity levels have increased unprecedentedly over the past couple of decades. Although the prevalence, trends and associated socio-economic factors of the condition have been extensively reported in Western populations, less is known regarding South Asian populations. Methods A review of articles using Medline with combinations of the MeSH terms: 'Obesity', 'Overweight' and 'Abdominal Obesity' limiting to epidemiology and South Asian countries. Results Despite methodological heterogeneity and variation according to country, area of residence and gender , the most recent nationally representative and large regional data demonstrates that without any doubt there is a epidemic of obesity, overweight and abdominal obesity in South Asian countries. Prevalence estimates of overweight and obesity (based on Asian cut-offs: overweight ≥ 23 kg/m(2), obesity ≥ 25 kg/m(2)) ranged from 3.5% in rural Bangladesh to over 65% in the Maldives. Abdominal obesity was more prevalent than general obesity in both sexes in this ethnic group. Countries with the lowest prevalence had the highest upward trend of obesity. Socio-economic factors associated with greater obesity in the region included female gender, middle age, urban residence, higher educational and economic status. Conclusion South Asia is significantly affected by the obesity epidemic. Collaborative public health interventions to reverse these trends need to be mindful of many socio-economic constraints in order to provide long-term solutions.

A meta-analytic clarification of the relationship between posttraumatic growth and symptoms of posttraumatic distress disorder

Traumatic experiences can have a powerful impact on individuals and communities but the relationship between perceptions of beneficial and pathological outcomes are not known. Therefore, this meta-analysis examined both the strength and the linearity of the relationship between symptoms of posttraumatic stress disorder (PTSD) and perceptions of posttraumatic growth (PTG) as well as identifying the potential moderating roles of trauma type and age. Literature searches of all languages were conducted using the ProQuest, Wiley Interscience, ScienceDirect, Informaworld and Web of Science databases. Linear and quadratic (curvilinear) rs as well as βs were analysed. Forty-two studies (N=11, 469) that examined both PTG and symptoms of PTSD were included in meta-analytic calculations. The combined studies yielded a significant linear relationship between PTG and PTSD symptoms (r=.315, CI = 0.299, 0.331), but also a significantly stronger (as tested by Fisher’s transformation) curvilinear relationship (r=.372, CI = 0.353, 0.391). The strength and linearity of these relationships differed according to trauma type and age. The results remind those working with traumatised people that positive and negative post-trauma outcomes can co-occur. A focus only on PTSD symptoms only may limit or slow recovery and mask the potential for growth.

Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear

Although the endocannabinoid system (ECS) has been implicated in brain development and various psychiatric disorders, precise mechanisms of the ECS on mood and anxiety disorders remain unclear. Here, we have investigated developmental and disease-related expression pattern of the cannabinoid receptor 1 (CB1) and the cannabinoid receptor 2 (CB2) genes in the dorsolateral prefrontal cortex (PFC) of humans. Using mice selectively bred for high and low fear, we further investigated potential association between fear memory and the cannabinoid receptor expression in the brain. The CB1, not the CB2, mRNA levels in the PFC gradually decrease during postnatal development ranging in age from birth to 50 years (r 2 > 0.6 & adj. p < 0.05). The CB1 levels in the PFC of major depression patients were higher when compared to the age-matched controls (adj. p < 0.05). In mice, the CB1, not the CB2, levels in the PFC were positively correlated with freezing behavior in classical fear conditioning (p < 0.05). These results suggest that the CB1 in the PFC may play a significant role in regulating mood and anxiety symptoms. Our study demonstrates the advantage of utilizing data from postmortem brain tissue and a mouse model of fear to enhance our understanding of the role of the cannabinoid receptors in mood and anxiety disorders

Prevalence of depressive symptoms as elicited by Patient Health Questionnaire (PHQ-9) among medical trainees in Oman

Background Despite the increasing recognition that medical training tends to coincide with markedly high levels of stress and distress, there is a dearth of validated measures that are capable of gauging the prevalence of depressive symptoms among medical residents in the Arab/Islamic part of the world. Objective The aim of the present study is two-fold. First is to examine the diagnostic validity of the Patient Health Questionnaire (PHQ-9) using an Omani medical resident population in order to establish a cut-off point. Second is to compare gender, age, and residency level among Omani Medical residents who report current depressive symptomatology versus those who report as non-depressed according to PHQ-9 cut-off threshold. Results A total of 132 residents (42 males and 90 females) consented to participate in this study. The cut-off score of 12 on the PHQ-9 revealed a sensitivity of 80.6% and a specificity of 94.0%. The rate of depression, as elicited by PHQ-9, was 11.4%. The role of gender, age, and residency level was not significant in endorsing depression. Conclusion This study indicated that PHQ-9 is a reliable measure among this cross-cultural population. More studies employing robust methodology are needed to confirm this finding.

Demystifying paradoxical characteristics of narcissistic personality disorder

This letter is aimed for psychotherapy clinicians and researchers who should acknowledge the relationship linking Kohut's self-psychology and Glasser's Choice theory that can demystify relationship difficulties and mental health problems in narcissistic personality disorder (NPD).

Results of the Queensland 2007-2012 roadside drug testing program : the prevalence of three illicit drugs

The purpose of this investigation is to present an overview of roadside drug driving enforcement and detections in Queensland, Australia since the introduction of oral fluid screening. Drug driving is a problematic issue for road safety and investigations of the prevalence and impact of drug driving suggest that, in particular, the use of illicit drugs may increase a driver’s involvement in a road crash when compared to a driver who is drug free. In response to the potential increased crash involvement of drug impaired drivers, Australian police agencies have adopted the use of oral fluid analysis to detect the presence of illicit drugs in drivers. This paper describes the results of roadside drug testing for over 80,000 drivers in Queensland, Australia, from December 2007 to June 2012. It provides unique data on the prevalence of methamphetamine, cannabis and ecstasy in the screened population for the period. When prevalence rates are examined over time, drug driving detection rates have almost doubled from around 2.0% at the introduction of roadside testing operations to just under 4.0% in the latter years. The most common drug type detected was methamphetamine (40.8%) followed by cannabis (29.8%) and methamphetamine/cannabis combination (22.5%). By comparison, the rate of ecstasy detection was very low (1.7%). The data revealed a number of regional, age and gender patterns and variations of drug driving across the state. Younger drivers were more likely to test positive for cannabis whilst older drivers were more likely to test positive for methamphetamine. The overall characteristics of drivers who tested positive to the presence of at least one of the target illicit drugs are they are likely to be male, aged 30-39 years, be driving a car on Friday, Saturday or Sunday between 6:00PM and 6:00AM and to test positive for methamphetamine.