Colonization of host mucus surfaces is one of the first steps in the establishment of coral-associated microbial communities. Coral mucus contains a sulfated glycoprotein (in which oligosaccharide decorations are connected to the polypeptide backbone by a mannose residue) and molecules that result from its degradation. Mucus is utilized as a growth substrate by commensal and pathogenic organisms. Two representative coral commensals, Photobacterium mandapamensis and Halomonas meridiana, differed from a white pox pathogen Serratia marcescens PDL100 in the pattern with which they utilized mucus polymers of Acropora palmata. Incubation with the mucus polymer increased mannopyranosidase activity in S. marcescens, suggestive of its ability to cleave off oligosaccharide side chains. With the exception of glucosidase and N-acetyl galactosaminidase, glycosidases in S. marcescens were subject to catabolite regulation by galactose, glucose, arabinose, mannose and N-acetyl-glucosamine. In commensal P. mandapamensis, at least 10 glycosidases were modestly induced during incubation on coral mucus. Galactose, arabinose, mannose, but not glucose or N-acetyl-glucosamine had a repressive effect on glycosidases in P. mandapamensis. Incubation with the mucus polymers upregulated 3 enzymatic activities in H. meridiana; glucose and galactose appear to be the preferred carbon source in this bacterium. Although all these bacteria were capable of producing the same glycosidases, the differences in the preferred carbon sources and patterns of enzymatic activities induced during growth on the mucus polymer in the presence of these carbon sources suggest that to establish themselves within the coral mucus surface layer commensals and pathogens rely on different enzymatic activities.

Access with evidence development (AED) describes the general approach of linking some form of access to the healthcare market with the generation of additional evidence relating to the value of the healthcare intervention under evaluation, with an explicit aim of aiding future decision making. A number of health systems around the world are interested in the potential for such schemes. This article looks in detail at the potential for some form of AED in the UK, focusing on the two major decision-making bodies: the Scottish Medicines Consortium in Scotland and the National Institute for Health and Clinical Excellence in England and Wales. We consider past experience with these approaches and current initiatives that are exploring their potential, and speculate as to how these schemes might develop in the future.

INTRODUCTION: Psychiatric disorders, mainly depression and anxiety, are frequently encountered in primary care and are a major cause of distress and disability. Nearly half of cases go unnoticed and among those that are recognised, many do not receive adequate treatment. In France, there is limited research concerning the prevalence, detection and management of these conditions in primary care. OBJECTIVES: To estimate the prevalence of psychiatric disorders, overall and for the main psychiatric diagnostic categories, encountered in primary care; to describe general practitioners'(GPs') case identification rate; to examine psychotropic medication prescription according to diagnosis, in a regionally representative sample of GP attenders. METHODS: GP practicing standard general practice in an urban area of the city of Montpellier and a nearby semi-rural region were recruited to participate. The response rate was 32.8%(n=41). Five additional GP almost exclusively offering homeopathy and acupuncture were recruited nonrandomly for convenience purposes. In each GP surgery, consecutive patients entering the waiting room were invited by a research assistant to participate until 25 patients per GP were recruited. Each participant completed self-report questionnaires in the waiting time, including the patient health questionnaire (PHQ), which yields provisional DSM-IV diagnoses. The GP completed a brief questionnaire during the consultation, giving his/her rating of the severity of any psychiatric disorder present and action taken. RESULTS: The patient response rate was 89.8%. In all, 14.9% of patients reached DSM-IV criteria for major depression or anxiety disorder on the PHQ (9.1% for major depression, 7.5% for panic disorder; 6% for other anxiety disorders). For the subthreshold categories, 7.4% met criteria for other depressive disorders, 11.8% for somatoform disorders and 10.9% for probable alcohol abuse or dependence. 66.3% of patients with DSM-IV diagnoses of major depression or anxiety disorder were identified by the GP as having a psychiatric disorder. The identification rate was 51% for all depressive disorders, anxiety and somatoform disorders. Of patients receiving a prescription for anxiolytic or antidepressant medication on the survey day, 80% were classified as cases of psychiatric disorder by the GP. Only 48.8% met criteria for major depression or anxiety disorder on the PHQ. CONCLUSION: This study highlights the frequency of psychiatric disorders in a regional study of French general practice. Overall, prevalence rates were similar to those found elsewhere, except for probable alcohol abuse and dependence, which was considerably higher than in the USA PHQ validation study. As in other countries, GP identified roughly half of psychiatric cases. Furthermore, half of patients treated by anxiolytic or antidepressant medication did not meet the diagnostic criteria on the survey day for which these medications have mainly shown their efficacy. This confirms the French paradox of one of the highest psychotropic medication consumption rates in Europe despite many cases of depression remaining untreated. The PHQ could be a rapid and acceptable diagnostic aid tool for French general practice but first needs to be validated against the diagnosis of mental health professionals in this setting.

OBJECTIVES: To assess the association between systemic C-reactive protein (CRP) and incident coronary heart disease (CHD) in community-dwelling elderly people. DESIGN: A French population-based multicenter prospective cohort study. SETTING: Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast. PARTICIPANTS: After 4 years of follow-up, a case-cohort study was designed including 1,004 subjects randomly selected from the initial cohort of 9,294 subjects free of CHD at baseline and 174 subjects who developed first CHD events during follow-up. MEASUREMENTS: Hazard ratios (HRs) were estimated using a Cox proportional hazard model adapted for the case-cohort design using a CRP level less than 1 mg/L as the reference category. RESULTS: Of the random sample, 24.3% had a CRP level less than 1.0 mg/L, 45.8% had a CRP level of 1.0 to 2.9 mg/L, and 29.9% had a CRP level of 3.0 to 10.0 mg/L. The HRs for CHD, adjusted for age, sex, and study center, were 1.69 (95% confidence interval (CI)=1.04-2.75) for CRP from 1.0 to 2.9 mg/L and 2.32 (95% CI=1.41-3.82) for CRP from 3.0 to 10.0 mg/L (P for trend <.001). After additional adjustment for smoking, body mass index, diabetes mellitus, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, statin use, and antihypertensive treatment, a baseline CRP of 3.0 to 10.0 mg/L remained associated with risk of CHD (HR=1.87, 95% CI=1.09-3.25), although CRP did not improve the discriminative ability of a predicting model based on traditional risk factors (receiver operating characteristic curves from 0.740 to 0.749). CONCLUSION: CRP is an independent CHD risk marker but does not improve CHD risk prediction in community-dwelling elderly people.

BACKGROUND: Few studies have assessed the relationship between triglycerides and the risk of hemorrhagic stroke, which contrasts the considerable number of studies about triglycerides and ischemic vascular events. We analyzed the association pattern between triglycerides and incident intracerebral hemorrhage as compared with coronary events and ischemic stroke, in a large cohort of elderly. METHODS: Population-based, prospective cohort study among 8393 men and women participating in the Three-City Study, aged >/=65 years at baseline. Fasting blood lipids, including triglycerides, were measured at baseline. Fatal and non-fatal strokes and coronary events were adjudicated and validated by scientific committees. Cox proportional hazards models were used to adjust for potential confounders. RESULTS: During a mean follow-up of 5.0 years, 36 hemorrhagic strokes, 143 ischemic strokes, and 393 coronary events occurred. An increased level of triglycerides was associated with an increased risk of ischemic vascular events. Conversely, a low level of triglycerides (</=0.94mmol/L) was associated with an increased risk of hemorrhagic stroke (adjusted hazard ratio 2.35; 95% confidence interval 1.18-4.70). The relationship with hemorrhagic stroke was mainly apparent in men, in individuals with high blood pressure, and in those with low levels of cholesterol. CONCLUSIONS: In this large cohort of elderly men and women, low triglycerides levels were associated with an increased risk of hemorrhagic stroke and a decreased risk of ischemic vascular events. The association between triglycerides and hemorrhagic stroke was particularly strong in men, in subjects with high blood pressure and in those with low cholesterol levels.

OBJECTIVES: To examine the association between hormone therapy (HT) and cognitive performance or dementia, focusing on the duration and type of treatment used, as well as the timing of initiation of HT in relation to the menopause. METHODS: Women 65 years and older were recruited in France as part of the Three City Study. At baseline and 2- and 4-year follow-up, women were administered a short cognitive test battery and a clinical diagnosis of dementia was made. Detailed information was also gathered relating to current and past HT use. Analysis was adjusted for a number of sociodemographic, behavioral, physical, and mental health variables, as well as APOE epsilon4. RESULTS: Among 3,130 naturally postmenopausal women, current HT users performed significantly better than never users on verbal fluency, working memory, and psychomotor speed. These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial. However, initiation of HT close to the menopause was not associated with better cognition. HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with APOE epsilon4. CONCLUSIONS: Current hormone therapy (HT) was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used. We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life. Current HT may decrease the risk of dementia associated with the APOE epsilon4 allele.

Glutathione transferases are a multigene family of proteins that catalyze the conjugation of toxic electrophiles and carcinogens to glutathione. Glutathione transferase Pi (GSTP) is commonly overexpressed in human tumors and there is emerging evidence that the enzyme has additional cellular functions in addition to its role in drug and carcinogen detoxification. To investigate the unique functions of this enzyme, we have crossed Gstp null mice with an initiated model of colon cancer, the Apc(Min) mouse. In contrast to the Apc(Min)(/+) Gstp1/p2(+/+)(Gstp-wt Apc(Min)) mice, which rarely develop colonic tumours, Apc(Min/+)Gstp1/p2(-/-)(Gstp-null Apc(Min)) mice had a 6-fold increase in colon adenoma incidence, and a 50-fold increase in colorectal adenoma multiplicity, relative to Gstp-wt Apc(Min). This increase was associated with early tumor onset and decreased survival. Analysis of the biochemical changes in the colon tissue of Gstp-null Apc(Min) mice demonstrated a marked induction of many inflammatory genes, including IL-6, IL-4, IFN-gamma, and inducible nitric oxide synthase. In support of the induction of inducible nitric oxide synthase, a profound induction of nitrotyrosine adducts was observed. Gstp therefore appears to play a role in controlling inflammatory responses in the colon, which would explain the change in tumor incidence observed. These data also suggest that individual variation in GSTP levels may be a factor in colon cancer susceptibility.

A cell's form and function is determined to a great extent by its cellular membrane and the underlying cytoskeleton. Understanding changes in the cellular membrane and cytoskeleton can provide insight into aging and disease of the cell. The Atomic Force Microscope (AFM) allows unparalled resolution for the imaging of these cellular components and the ability to probe their mechanical properties. This report describes our progress toward the use of AFM as a tool in neuroscience applications. Elasticity measurements are reported on living chick embryo dorsal root ganglion and sympathetic neurons in vitro. The neuronal cellular body and growth cones regions are examined for variations in cellular maturity. In addition, cellular changes due to exposure to various environmental conditions and neurotoxins are investigated. This report includes data obtained on different AFM systems, using various AFM techniques and thus also provides knowledge of AFM instruments and methodology.

Background: Olive oil is a major component of the Mediterranean diet suggested to be beneficial to counteract Alzheimer's disease. Aim of the Study: Our objective was to examine the association between olive oil use, cognitive deficit and cognitive decline in a large elderly population. Methods: We followed 6,947 subjects with a brief baseline food frequency questionnaire and repeated cognitive tests. Olive oil intake was categorized as none (22.7%), moderate (use for cooking or dressing, 39.9%) and intensive (use for both cooking and dressing, 37.4%). Associations between olive oil and cognitive outcomes were examined taking into account socio-economic factors, health behaviors, health measures and other dietary intakes. Results: Participants with moderate or intensive use of olive oil compared to those who never used olive oil showed lower odds of cognitive deficit for verbal fluency and visual memory. For cognitive decline during the 4-year follow-up, the association with intensive use was significant for visual memory (adjusted OR = 0.83, 95% CI: 0.69-0.99) but not for verbal fluency (OR = 0.85, 95% CI: 0.70-1.03) in multivariate analysis. Conclusions: This olive oil-cognition association needs to be confirmed by further studies. However, our findings already shed light on the potential importance of olive oil in the Mediterranean diet and on its beneficial effects on health.

OBJECTIVE: Depression in the elderly is common and often resistant to treatment. It has been suggested that late-life depression may be related to underlying neurobiological changes. However, these observations are derived from diverse clinical samples and as yet have not been confirmed in a more representative population study. Our aim was to investigate associations between neurological signs as markers of underlying brain dysfunction and caseness for depression in an elderly community sample, controlling for physical health and comorbid/past neurological disorders. METHOD: A cross-sectional analysis of 2102 older people without dementia from the ESPRIT project. Depressive symptomatology was ascertained using the CES-D and abnormal neurological signs/comorbidity from a full neurological examination according to ICD-10 criteria. RESULTS: Pyramidal, extrapyramidal, cranial nerve and sensory deficit signs were significantly associated with case-level depressive symptoms. However, all odds ratios were close to null values in participants who did not have previous neurological disorder. CONCLUSIONS: We confirmed previous findings of an association between neurological signs and case-level depressive symptoms in late life. However, this association may simply reflect the impact of more severe comorbid neurological disorder. Copyright (c) 2009 John Wiley & Sons, Ltd.