Depression and cardiovascular morbidity and mortality: cause or consequence?

Background Depression after myocardial infarction has been associated with increased cardiovascular mortality. This study assessed whether depressive symptoms were associated with adverse outcomes in people with a history of an acute coronary syndrome, and evaluated possible explanations for such an association. Methods and results Depressive symptoms were assessed using the General Health Questionnaire at least 5 months after hospital admission for acute myocardial infarction or unstable angina in 1130 participants of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study, a multicentre, placebo-controlled, clinical trial of cholesterol-lowering treatment. Cardiovascular symptoms, self-rated general health, cardiovascular risk factors, employment status, social support and life events were also assessed at the baseline visit. Cardiovascular death (n=114), non-fatal myocardial infarction (n=108), non-fatal stroke (n=53) and unstable angina (n=274) were documented during a median follow-up period of 8.1 years. Individuals with depressive symptoms (General. Health Questionnaire score greater than or equal to5; 22% of participants) were more likely to report angina, dyspnoea, claudication, poorer general health, not being in paid employment, few social contacts and/or adverse life events (P

Laparoscopic Swenson procedure - An optimal approach for both primary and secondary pull-through for Hirschsprung's disease

Background/Purpose: Several pull-through procedures are available for the surgical management of Hirschsprung's disease (HD) in children. The authors have adopted a laparoscopic approach since 1995, including laparoscopic Swenson procedure (LSw), both for one-stage primary and 2-stage secondary procedures. The aim of this study was to examine the role of LSw in children with HD in both primary and secondary procedures. Methods: From January 1995 to December 2001, 42 children with biopsy-proven HD underwent laparoscopic pull-through procedure for HD. This group included 29 children who underwent LSw, a detailed analysis of which forms the basis of this report. Results: Sixteen children underwent a single-stage neonatal LSw; the median weight of this group at the time of surgery was 3.2 kg and the median age was 5 days. Secondary LSw was performed in the remaining 13 children, which included 3 children with total colonic HD who underwent laparoscopic total colectomy and LSw. The median operating time was 105 minutes (range, 66 to 175 minutes). The median time to commence full diet was 48 hours (range, 24 to 86 hours), and median time to return to normal play and activity was 72 hours (range, 48 hours to 5 days). There was no difference in operating time between primary and secondary pull-through procedures. There were no intraoperative complications, and no patient required open conversion. Postoperative ileus was noted in 3 children and enterocolitis in 2. The median hospital stay was 4 days (range, 2 to 6 days). Follow-up was between 6 months to 7 years with a median follow-up of 2.2 years. At follow-up, 2 children required laparoscopic antegrade continence enema procedure. A satisfactory continence was noted in 15 of the 19 children who were older than 3 years at the time of last follow-up. Conclusions: LSw seems to be a suitable procedure for laparoscopic management of HD in children. LSw is safe and effective, both for primary and secondary type of pull-through procedures, with good short-term results.

Divergent environments and population bottlenecks fail to generate premating isolation in Drosophila pseudoobscura

While the feasibility of bottleneck-induced speciation is in doubt, population bottlenecks may still affect the speciation process by interacting with divergent selection. To explore this possibility, I conducted a laboratory speciation experiment using Drosophila pseudoobscura involving 78 replicate populations assigned in a two-way factorial design to both bottleneck (present vs. absent) and environment (ancestral vs. novel) treatments. Populations independently evolved under these treatments and were then tested for assortative mating and male mating success against their common ancestor. Bottlenecks alone did not generate any premating isolation, despite an experimental design that was conducive to bottleneck-induced speciation. Premating isolation also did not evolve in the novel environment treatment, neither in the presence nor absence of bottlenecks. However, male mating success was significantly reduced in the novel environment treatment, both as a plastic response to this environment and as a result of environment-dependent inbreeding effects in the bottlenecked populations. Reduced mating success of derived males will hamper speciation by enhancing the mating success of immigrant, ancestral males. Novel environments are generally thought to promote ecological speciation by generating divergent natural selection. In the current experiment, however, the novel environment did not cause the evolution of any premating isolation and it reduced the likelihood of speciation through its effects on male mating success.

Predictive genetic test decisions for Huntington's disease: context, appraisal and new moral imperatives

Predictive testing is one of the new genetic technologies which, in conjunction with developing fields such as pharmacogenomics, promises many benefits for preventive and population health. Understanding how individuals appraise and make genetic test decisions is increasingly relevant as the technology expands. Lay understandings of genetic risk and test decision-making, located within holistic life frameworks including family or kin relationships, may vary considerably from clinical representations of these phenomena. The predictive test for Huntington's disease (HD), whilst specific to a single-gene, serious, mature-onset but currently untreatable disorder, is regarded as a model in this context. This paper reports upon a qualitative Australian study which investigated predictive test decision-making by individuals at risk for HD, the contexts of their decisions and the appraisals which underpinned them. In-depth interviews were conducted in Australia with 16 individuals at 50% risk for HD, with variation across testing decisions, gender, age and selected characteristics. Findings suggested predictive testing was regarded as a significant life decision with important implications for self and others, while the right not to know genetic status was staunchly and unanimously defended. Multiple contexts of reference were identified within which test decisions were located, including intra- and inter-personal frameworks, family history and experience of HID, and temporality. Participants used two main criteria in appraising test options: perceived value of, or need for the test information, for self and/or significant others, and degree to which such information could be tolerated and managed, short and long-term, by self and/or others. Selected moral and ethical considerations involved in decision-making are examined, as well as the clinical and socio-political contexts in which predictive testing is located. The paper argues that psychosocial vulnerabilities generated by the availability of testing technologies and exacerbated by policy imperatives towards individual responsibility and self-governance should be addressed at broader societal levels. (C) 2003 Elsevier Science Ltd. All rights reserved.

Adaptation to being at-risk for Huntington's disease and the availability of genetic testing: Application of a stress and coping model

This study examined the utility of a stress/coping model in explaining adaptation in two groups of people at-risk for Huntington's Disease (HD): those who have not approached genetic testing services (non-testees) and those who have engaged a testing service (testees). The aims were (1) to compare testees and non-testees on stress/coping variables, (2) to examine relations between adjustment and the stress/coping predictors in the two groups, and (3) to examine relations between the stress/coping variables and testees' satisfaction with their first counselling session. Participants were 44 testees and 40 non-testees who completed questionnaires which measured the stress/coping variables: adjustment (global distress, depression, health anxiety, social and dyadic adjustment), genetic testing concerns, testing context (HD contact, experience, knowledge), appraisal (control, threat, self-efficacy), coping strategies (avoidance, self-blame, wishful thinking, seeking support, problem solving), social support and locus of control. Testees also completed a genetic counselling session satisfaction scale. As expected, non-testees reported lower self-efficacy and control appraisals, higher threat and passive avoidant coping than testees. Overall, results supported the hypothesis that within each group poorer adjustment would be related to higher genetic testing concerns, contact with HD, threat appraisals, passive avoidant coping and external locus of control, and lower levels of positive experiences with HD, social support, internal locus of control, self-efficacy, control appraisals, problem solving, emotional approach and seeking social support coping. Session satisfaction scores were positively correlated with dyadic adjustment, problem solving and positive experience with HD, and inversely related to testing concerns, and threat and control appraisals. Findings support the utility of the stress/coping model in explaining adaptation in people who have decided not to seek genetic testing for HD and those who have decided to engage a genetic testing service.

Ecological speciation

Ecological processes are central to the formation of new species when barriers to gene flow (reproductive isolation) evolve between populations as a result of ecologically-based divergent selection. Although laboratory and field studies provide evidence that 'ecological speciation' can occur, our understanding of the details of the process is incomplete. Here we review ecological speciation by considering its constituent components: an ecological source of divergent selection, a form of reproductive isolation, and a genetic mechanism linking the two. Sources of divergent selection include differences in environment or niche, certain forms of sexual selection, and the ecological interaction of populations. We explore the evidence for the contribution of each to ecological speciation. Forms of reproductive isolation are diverse and we discuss the likelihood that each may be involved in ecological speciation. Divergent selection on genes affecting ecological traits can be transmitted directly (via pleiotropy) or indirectly (via linkage disequilibrium) to genes causing reproductive isolation and we explore the consequences of both. Along with these components, we also discuss the geography and the genetic basis of ecological speciation. Throughout, we provide examples from nature, critically evaluate their quality, and highlight areas where more work is required.

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin

Background-Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. Methods and Results-We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1 X 10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2X10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased ( by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). Conclusions-These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

A comparison of the Yale-Brown obsessive compulsive scale for "Heavy drinking" with a single item craving measure: Construct validity and clinical utility

The measurement of alcohol craving began with single-item scales. Multifactorial scales developed with the intention to capture more fully the phenomenon of craving. This study examines the construct validity of a multifactorial scale, the Yale-Brown Obsessive Compulsive Scale for heavy drinking (Y-BOCS-hd). The study compares its clinical utility with a single item visual-analogue craving scale. The study includes 212 alcohol dependent subjects (127 males, 75 females) undertaking an outpatient treatment program between 1999-2001. Subjects completed the Y-BOCS-hd and a single item visual-analogue scale, in addition to alcohol consumption and dependence severity measures. The Y-BOCS-hd had strong construct validity. Both the visual-analogue alcohol craving scale and Y-BOCS-hd were weakly associated with pretreatment dependence severity. There was a significant association between pretreatment alcohol consumption and the visual-analogue craving scale. Neither craving measure was able to predict total program abstinence or days abstinent. The relationship between obsessive-compulsive behavior in alcohol dependence and craving remains unclear.

Evaluation of eight spring onion genotypes, sulphur nutrition and soil-type effects with an electronic nose

Genotype, sulphur (S) nutrition and soil-type effects on spring onion quality were assessed using a 32-conducting polymer sensor E-nose. Relative changes in sensor resistance ratio (% dR/R) varied among eight spring onion genotypes. The % dR/R was reduced by S application in four of the eight genotypes. For the other four genotypes, S application gave no change in % dR/R in three, and increased % dR/R in the other. E-nose classification of headspace volatiles by a two-dimensional principal component analysis (PCA) plot for spring onion genotypes differed for S fertilisation vs. no S fertilisation. Headspace volatiles data set clusters for cv. 'White Lisbon' grown on clay or on sandy loam overlapped when 2.9 [Mahalanobis distance value (D2) = 1.6], or 5.8-(D2 = 0.3) kg S ha-1 was added. In contrast, clear separation (D2 = 7.5) was recorded for headspace volatile clusters for 0 kg S hd-1 on clay vs. sandy loam. Addition of 5.8 kg S ha-1 increased pyruvic acid content (mmole g-1 fresh weight) by 1.7-fold on average across the eight genotypes. However, increased S from 2.9 to 5.8 kg ha-1 did not significantly (P > 0.05) influence % dR/R, % dry matter (DM) or total soluble solids (TSS) contents, but significantly (P < 0.05) increased pyruvic acid content. TSS was significantly (P < 0.05) reduced by S addition, while % DM was unaffected. In conclusion, the 32-conducting polymer E-nose discerned differences in spring onion quality that were attributable to genotype and to variations in growing conditions as shown by the significant (P < 0.05) interaction effects for % dR/R.

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Gender differences in attitudes among those at risk for Huntington's disease

This report presents and discusses selected findings regarding gender differences from an Australian-based study that investigated attitudes of individuals at risk for Huntington's disease (HD) towards genetic risk and predictive testing. Clear gender differences emerged regarding perceived coping capacity with regard to predictive testing, as well as disclosure of the genetic risk for HD to others. Female participants were more likely to disclose their genetic risk to others, including their medical practitioners, while male participants were three times more fearful of disclosing their genetic risk to others. These findings are of interest in light of gender differences that have consistently been reported regarding the uptake of predictive testing for HD, other genetic conditions, and health services more generally. While gender differences cannot provide a fully explanatory framework for differential uptake of predictive genetic testing, men and women may experience and respond differently to the genetic risk for HD and possibly other inherited disorders. The meanings of genetic risk to men and women warrants further exploration, given anticipated increases in genetic testing for more common conditions, especially if post-test interventions are possible. These issues are also relevant within the context of individuals' concerns about the potential for discrimination on the basis of genetic risk or genetic test information.

Predictive genetic test decisions for Huntington's disease: Elucidating the test/no-test dichotomy

Predictive genetic testing for serious, mature-onset genetic illness represents a unique context in health decision making. This article presents findings from an exploratory qualitative Australian-based study into the decision making of individuals at risk for Huntington's disease (HD) with regard to predictive genetic testing. Sixteen in-depth interviews were conducted with a range of at-risk individuals. Data analysis revealed four discrete decision-making positions rather than a 'to test' or not to test' dichotomy. A conceptual dimension of (non-)openness and (non-)engagement characterized the various decisions. Processes of decision making and a concept of 'test readiness' were identified. Findings from this research, while not generalizable, are discussed in relation to theoretical frameworks and stage models of health decision making, as well as possible clinical implications.

Animal production potential of some new Leucaena accessions in the Markham valley, Papua New Guinea

Signal grass pastures were oversown with four Leucaena spp. planted in hedgerows and evaluated for their agronomic productivity and ability to support steer liveweight gains. Each Leucaena sp. (L. leucocephala, L. pallida, L colli. nst. i., L. trichandra) was planted as seedlings into two I ha paddocks in rows 5 m apart, with I m spacing between trees. Cattle were rotationally grazed on the 2 replicates of each species, as well as on two I ha paddocks of a signal grass on y (Brachiaria decumbens) control, over a 243-day period at a stocking rate of 3 steers/ha. Mean presentation yield and herbage allowance of the Leucaena accessions over the grazing period were highest for L pallida (1100 kg/ha and 0.8 kg DM/kg LW, respectively), followed by L. leucocephala (700 kg/ha and 0.5 kg DM/kg LW), L. collinsii (700 kg/ha and 0.4 kg DM/kg LW) and L. trichandra (300 kg/ha and 0.2 kg DM/kg LW). Despite only moderate presentation yields and herbage allowances, steers grazing L. leucocephala and L. collinsii accessions produced the highest mean liveweight gains (LWG) of 0. and 0.56 kg/hd/d, respectively. While L. pallida produced the highest DM yields, it supported the lowest LWG of 0.36 kg/hd/d. The mean LWGs of steers grazing L. trichandra and the control (grass only) treatments were similar at 0.48 kg/ hd/d. The possible reasons for the differences in steer performance on the different Leucaena accessions are discussed.

Developmental expression of transcription factor genes in a demosponge: insights into the origin of metazoan multicellularity

Demosponges are considered part of the most basal evolutionary lineage in the animal kingdom. Although the sponge body plan fundamentally differs from that of other metazoans, their development includes many of the hallmarks of bilaterian and eumetazoan embryogenesis, namely fertilization followed by a period of cell division yielding distinct cell populations, which through a gastrulation-like process become allocated into different cell layers and patterned within these layers. These observations suggest that the last common ancestor (LCA) to all living animals was developmentally more sophisticated than is widely appreciated and used asymmetric cell division and morphogen gradients to establish localized populations of specified cells within the embryo. Here we demonstrate that members of a range of transcription factor gene classes, many of which appear to be metazoan-specific, are expressed during the development of the demosponge Reniera, including ANTP, Pax, POU, LIM-HD, Sox, nuclear receptor, Fox (forkhead), T-box, Mef2, and Ets genes. Phylogenetic analysis of these genes suggests that not only the origin but the diversification of some of the major developmental metazoan transcription factor classes took place before sponges diverged from the rest of the Metazoa. Their expression during demosponge development suggests that, as in today's sophisticated metazoans, these genes may have functioned in the regulatory network of the metazoan LCA to control cell specification and regionalized gene expression during embryogenesis.

Mapping the emergence of heart disease in a black, urban population in Africa: The Heart of Soweto Study

Background: There is increasing evidence that many populations in the developing world are in epidemiologic transition with the subsequent emergence of more affluent disease states. The Heart of Soweto Study will systematically investigate the emergence of heart disease (HD) in a large urban population in South Africa. Methods: Part of the conurbation of Johannesburg, South Africa, Soweto is a predominantly Black African community of I million individuals. During an initial two year period, all individuals presenting to the local Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic and diagnostic coding data in those with pre-established HD will form an abbreviated clinical registry of > 12,000 prevalent cases. Similarly, socio-demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in newly diagnosed patients will form a more detailed clinical registry of > 5000 incident cases. Sub-studies of the relationship between HIV status and H D and the optimal management of chronic heart failure will also be performed. Results: These data will provide a unique insight into the causes and consequences of a broad spectrum of HD-related conditions in a developing world community in epidemiologic transition. Initially documented Population rates, in addition to detailed examinations of the underlying risk factors and causes of HD-related morbidity/mortality will provide an important platform for future stages of the study: a community-based, population screening program and culturally specific primary and secondary programs of care. Conclusion: There is an urgent need to systematically track the emergence of HD in the developing world. Initially involving more than 15,000 individuals, the unique Heart of Soweto Study has the potential to provide a wealth of information in this regard. (c) 2006 Elsevier Ireland Ltd. All rights reserved.