Polymorphisms in the 5 '-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression

We present evidence of complex balancing regulation of HTR1B transcription by common polymorphisms in its promoter. Computational analysis of the HTR1B gene predicted that a 50 segment, spanning common DNA sequence variations, T-261G, A-161T, and -182INS/DEL-181, contained a putative functional promoter. Using a secreted alkaline phosphatase (SEAP) reporter gene system, we found that the haplotype -261G_-182INS-181_A-161 enhanced transcriptional activity 2.3-fold compared with the haplotype T-261_-182INS-181_A-161. Conversely, -161T reversed this, and the net effect when -261G and -161T were in the same haplotype (-261G_-182INS-181_-161T) was equivalent to the major haplotype (T-261_-182INS-181_A-161). Electrophoretic mobility shift experiments showed that -261G and -161T modify the binding of transcription factors (TFs): -261G generates a new AP2 binding site, while alleles A-161 and -161T exhibit different binding characteristics to AP1. T-261G and A-161T were found to be in linkage disequilibrium (LD) with G861C in a European ancestry population. Interestingly, G861C has been reported to be associated with several psychiatric disorders. Our results indicate that HTR1B is the target of substantial transcriptional genetic regulation by common haplotypes, which are in LD with the HTR1B single-nucleotide polymorphism (SNP) most commonly used in association studies.

Population effects on individual systolic blood pressure: A multilevel analysis of the World Health Organization MONICA project

Individuals from the same population share a number of contextual circumstances that may condition a common level of blood pressure over and above individual characteristics. Understanding this population effect is relevant for both etiologic research and prevention strategies. Using multilevel regression analyses, the authors quantified the extent to which individual differences in systolic blood pressure (SBP) could be attributed to the population level. They also investigated possible cross-level interactions between the population in which a person lived and pharmacological (antihypertensive medication) and nonpharmacological (body mass index) effects on individual SBP. They analyzed data on 23,796 men and 24,986 women aged 35-64 years from 39 worldwide Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study populations participating in the final survey of this World Health Organization project (1989-1997). SBP was positively associated with low educational achievement, high body mass index, and use of antihypertensive medication and, for women, was negatively associated with smoking. About 7-8% of all SBP differences between subjects were attributed to the population level. However, this population effect was particularly strong (i.e., 20%) in antihypertensive medication users and overweight women. This empirical evidence of a population effect on individual SBP emphasizes the importance of developing population-wide strategies to reduce individual risk of hypertension.

Hypermethylation of the 5 ' CpG island of the gene encoding the serine protease Testisin promotes its loss in testicular tumorigenesis

The Testisin gene (PRSS21) encodes a glycosylphosphatidylinositol (GPI)-linked serine protease that exhibits testis tissue-specific expression. Loss of Testisin has been implicated in testicular tumorigenesis, but its role in testis biology and tumorigenesis is not known. Here we have investigated the role of CpG methylation in Testisin gene inactivation and tested the hypothesis that Testisin may act as a tumour suppressor for testicular tumorigenesis. Using sequence analysis of bisulphite-treated genomic DNA, we find a strong relationship between hypermethylation of a 385 bp 50 CpG rich island of the Testisin gene, and silencing of the Testisin gene in a range of human tumour cell lines and in 100% (eight/eight) of testicular germ cell tumours. We show that treatment of Testisin-negative cell lines with demethylating agents and/or a histone deacetylase inhibitor results in reactivation of Testisin gene expression, implicating hypermethylation in Testisin gene silencing. Stable expression of Testisin in the Testisin-negative Tera-2 testicular cancer line suppressed tumorigenicity as revealed by inhibition of both anchorage-dependent cell growth and tumour formation in an SCID mouse model of testicular tumorigenesis. Together, these data show that loss of Testisin is caused, at least in part, by DNA hypermethylation and histone deacetylation, and suggest a tumour suppressor role for Testisin in testicular tumorigenesis.

Effective leadership in salient groups: Revisiting leader-member exchange theory from the perspective of the social identity theory of leadership

Two studies compared leader-member exchange (LMX) theory and the social identity theory of leadership. Study 1 surveyed 439 employees of organizations in Wales, measuring Work group salience, leader-member relations, and perceived leadership effectiveness. Study 2 surveyed 128 members of organizations in India, measuring identification not salience and also individualism/collectivism. Both studies provided good support for social identity predictions. Depersonalized leader-member relations were associated with greater leadership effectiveness among high- than low-salient groups (Study 1) and among high than low identifiers (Study 2). Personalized leadership effectiveness was less affected by salience (Study 1) and unaffected by identification (Study 2). Low-salience groups preferred personalized leadership more than did high-salience groups (Study 1). Low identifiers showed no preference but high identifiers preferred depersonalized leadership (Study 2). In Study 2, collectivists did not Prefer depersonalized as opposed to personalized leadership, whereas individualists did, probably because collectivists focus more on the relational self.

Some economic dimensions of the mental health jigsaw in Australia

The purpose of this paper is to demonstrate that, although there are some unique features associated with mental illness, such special features do not preclude economic analysis. As a mechanism for understanding how individual economic studies fit into the mental health sector, a conceptual framework of the components of mental health service provision is outlined. Emphasis is placed on, not simply institutional and market resources, but also on the services provided by relatives, self-help groups, etc. Australian data on parts of the mental health sector are employed to illustrate that some (and different) economic analyses can be undertaken in mental health. First, time-series data on public psychiatric hospitals are employed to demonstrate trends associated with deinstitutionalisation. Other data (for Queensland alone) indicate that there are state-based differences in the provision of such services. Second, attention is then directed to the analysis of time-series data on private fee-for-service psychiatric services. Various concepts and measures from industrial economics are applied to analyse the relative size of this service industry, the pricing behaviour of the profession, the service-mix of "the psychiatry firms" operating in Australia.

Eating disorders and oral health: A review of the literature

This article is a review of the recent literature pertaining to the oral sequelae of eating disorders (EDs). Dentists are recognized as being some of the first health care professionals to whom a previously undiagnosed eating disorder patient (EDP) may present. However, despite the prevalence (up to 4 per cent) of such conditions in teenage girls and young adult females, there is relatively little published in the recent literature regarding the oral sequelae of EDs. This compares unfavourably with the attention given recently in the dental literature to conditions such as diabetes mellitus, which have a similar prevalence in the adult population. The incidence of EDs is increasing and it would be expected that dentists who treat patients in the affected age groups would encounter more individuals exhibiting EDs. Most of the reports in the literature concentrate on the obvious clinical features of dental destruction (perimolysis), parotid swelling and biochemical abnormalities particularly related to salivary and pancreatic amylase. However, there is no consistency in explanation of the oral phenomena and epiphenomena seen in EDs. Many EDPs are nutritionally challenged; there is a relative lack of information pertaining to non-dental, oral lesions associated with nutritional deficiencies.

Identification of two evolutionarily conserved and functional regulatory elements in intron 2 of the human BRCA1 gene

Cross-species comparative genomics is a powerful strategy for identifying functional regulatory elements within noncoding DNA. In this paper, comparative analysis of human and mouse intronic sequences in the breast cancer susceptibility gene (BRCA1) revealed two evolutionarily conserved noncoding sequences (CNS) in intron 2, 5 kb downstream of the core BRCA1 promoter. The functionality of these elements was examined using homologous-recombination-based mutagenesis of reporter gene-tagged cosmids incorporating these regions and flanking sequences from the BRCA1 locus. This showed that CNS-1 and CNS-2 have differential transcriptional regulatory activity in epithelial cell lines. Mutation of CNS-1 significantly reduced reporter gene expression to 30% of control levels. Conversely mutation of CNS-2 increased expression to 200% of control levels. Regulation is at the level of transcription and shows promoter specificity. Both elements also specifically bind nuclear proteins in vitro. These studies demonstrate that the combination of comparative genomics and functional analysis is a successful strategy to identify novel regulatory elements and provide the first direct evidence that conserved noncoding sequences in BRCA1 regulate gene expression. (c) 2005 Elsevier Inc. All rights reserved.

Ethical perspectives of the Australian live export trade

Objective To examine the ethical perspectives of the Australian live export trade. Design and method The perspectives of farmers and other industry personnel, overseas consumers, the Australian public, veterinarians and the assumed interests of transported animals are compared in relation to the ethical consequences. Animal welfare, societal, personal and professional ethics are identified and the ratification of different perspectives considered. Results and conclusions There are positive and negative aspects of the trade for each stakeholder group, and the overall position adopted by any individual reflects their perspective of the balance of these components. The debate as to whether Australia should continue with the trade will be best served by consideration of the interests of all parties in the trade, including the consumers and animals, which are among the most affected by the trade. There is a need for further research to address the major welfare problems for the animals, an openness to inspection on the part of the trade and balance in media reporting.

Identifying the energy gap: Magnitude and determinants of 5-year weight gain in midage women

Objective: The aims of this study were to estimate average yearly weight gain in midage women and to identify the determinants of weight gain and gaining weight at double the average rate. Research Methods and Procedures: The study sample comprised 8071 participants (45 to 55 years old) in the Australian Longitudinal Study on Women's Health who completed mailed surveys in 1996, 1998, and 2001. Results: On average, the women gained almost 0.5 kg per year [average 2.42 kg (95% confidence interval, 2.29 to 2.54) over 5 years]. In multivariate analyses, variables associated with energy balance (physical activity, sitting time, and energy intake), as well as quitting smoking, menopause/hysterectomy, and baseline BMI category were significantly associated with weight gain, but other behavioral and demographic characteristics were not. After adjustment for all of the other biological and behavioral variables, the odds of gaining weight at about twice the average rate (> 5 kg over 5 years) were highest for women who quit smoking (odds ratio = 2.94; 95% confidence interval, 2.17, 3.96). There were also independent relationships between the odds of gaining > 5 kg and lower levels of habitual physical activity, more time spent sitting, energy intake (but only in women with BMI > 25 at baseline), menopause transition, and hysterectomy. Discussion: The average weight gain equates with an energy imbalance of only about 10 kcal or 40 kJ per day, which suggests that small sustained changes in the modifiable behavioral variables could prevent further weight gain.

Health system reform in Mexico 5: Assessing the effect of the 2001-06 Mexican health reform: an interim report card

Since 2001, Mexico has been designing, legislating, and implementing a major health-system reform. A key component was the creation of Seguro Popular, which is intended to expand insurance coverage over 7 years to uninsured people, nearly half the total population at the start of 2001. The reform included five actions: legislation of entitlement per family affiliated which, with full implementation, will increase public spending on health by 0.8-1.0% of gross domestic product; creation of explicit benefits packages; allocation of monies to decentralised state ministries of health in proportion to number of families affiliated; division of federal resources flowing to states into separate funds for personal and non-personal health services; and creation of a fund to protect families against catastrophic health expenditures. Using the WHO health-systems framework, we used a wide range of datasets to assess the effect of this reform on different dimensions of the health system. Key findings include: affiliation is preferentially reaching the poor and the marginalised communities; federal non-social security expenditure in real per-head terms increased by 38% from 2000 to 2005; equity of public-health expenditure across states improved; Seguro Popular affiliates used more inpatient and outpatient services than uninsured people; effective coverage of 11 interventions has improved between 2000 and 2005-06; inequalities in effective coverage across states and wealth deciles has decreased over this period; catastrophic expenditures for Seguro Popular affiliates are lower than for uninsured people even though use of services has increased. We present some lessons for Mexico based on this interim evaluation and explore implications for other countries considering health reforms.