Reservoir-Excess Pressure Parameters Independently Predicts Cardiovascular Events in Individuals With Type 2 Diabetes.

The parameters derived from reservoir-excess pressure analysis have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM and whether they would predict cardiovascular events in individuals with T2DM. We studied 306 people with T2DM with cardiovascular disease (CVD; DMCVD, 70.4±7.8 years), 348 people with T2DM but without CVD (diabetes mellitus, 67.7±8.4 years), and 178 people without T2DM or CVD (control group [CTRL], 67.2±8.9 years). Reservoir-excess pressure analysis-derived parameters, including reservoir pressure integral, peak reservoir pressure, excess pressure integral, systolic rate constant, and diastolic rate constant, were obtained by radial artery tonometry. Reservoir pressure integral was lower in DMCVD diabetes mellitus and than CTRL. Peak reservoir pressure was lower, and excess pressure integral was greater in DMCVD diabetes mellitus than and CTRL. Systolic rate constant was lower in a stepwise manner among groups (DMCVD< diabetes mellitus <CTRL). Diastolic rate constant was greater in DMCVD than CTRL. In the subgroup of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9 noncardiovascular causes), and 108 cardiovascular events occurred during a 3-year follow-up period. Logistic regression analysis revealed that reservoir pressure integral (odds ratio, 0.59 [95% CI, 0.45-0.79]) and diastolic rate constant (odds ratio, 1.60 [95% CI, 1.25-2.06]) were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors (both P<0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered reservoir-excess pressure analysis-derived parameters are associated with T2DM. Furthermore, baseline values of reservoir pressure integral and diastolic rate constant independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM

The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. METHODS: 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. RESULTS: People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA1c accounted for the effects of T2DM. HbA1c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (β) -0.096, p = <0.008 and -0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (β -0.099; p = 0.006 and -0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA1c and ACh (β -0.043; p = 0.3), but not between HbA1c and SNP (β -0.105; p = 0.02). CONCLUSIONS: In those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for "advanced disease" than concomitant CVD, although this requires prospective validation.This received support from the Innovative Medicines Initiative Joint Undertaking under the Grant Agreement No. 115006; http://www.imi-summit.eu

Worries about being judged versus being harmed: Disentangling the association of social anxiety and paranoia with schizotypy

Paranoia is a dimension of clinical and subclinical experiences in which others are believed to have harmful intentions. Mild paranoid concerns are relatively common in the general population, and more clinically severe paranoia shares features with social anxiety and is a key characteristic of schizotypy. Given that subclinical manifestations of schizotypy and paranoia may predict the occurrence of more severe symptoms, disentangling the associations of these related constructs may advance our understanding of their etiology; however no known studies to date have comprehensively evaluated how paranoia relates to social anxiety and schizotypy. The current research sought to examine the association of paranoia, assessed across a broad continuum of severity, with 1) the positive and negative schizotypy dimensions and 2) social anxiety. Specifically, the study tested a series of six competing, a priori models using confirmatory factor analysis in a sample of 862 young adults. As hypothesized, the data supported a four-factor model including positive schizotypy, negative schizotypy, social anxiety, and paranoia factors, suggesting that these are distinct constructs with differing patterns of interrelationships. Paranoia had a strong association with positive schizotypy, a moderate association with social anxiety, and a minimal association with negative schizotypy. The results are consistent with paranoia being part of a multidimensional model of schizotypy and schizophrenia. Prior studies treating schizotypy and schizophrenia as homogenous constructs often produce equivocal or non-replicable results because these dimensions are associated with distinct etiologies, presentations, and treatment responses; thus, the present conceptualization of paranoia within a multidimensional schizotypy framework should advance our understanding of these constructs. © 2014 Horton et al

Experience of Pleasure and Emotional Expression in Individuals with Schizotypal Personality Features

Difficulties in feeling pleasure and expressing emotions are one of the key features of schizophrenia spectrum conditions, and are significant contributors to constricted interpersonal interactions. The current study examined the experience of pleasure and emotional expression in college students who demonstrated high and low levels of schizotypal personality disorder (SPD) traits on self-report questionnaires. One hundred and seventeen subjects with SPD traits and 116 comparison controls were recruited to participate. Cluster analyses conducted in the SPD group identified negative SPD and positive SPD subgroups. The negative SPD group exhibited deficient emotional expression and anticipatory pleasure, but showed intact consummatory pleasure. The positive SPD group reported significantly greater levels of anticipatory, consummatory and total pleasure compared to the control group. Both SPD groups reported significantly more problems in everyday memory and greater levels of depressive and anxiety-related symptoms

Patterns of genetic diversity and differentiation in the tsetse fly Glossina morsitans morsitans Westwood populations in East and southern Africa

Genetic diversity and differentiation within and among nine G. morsitans morsitanspopulations from East and southern Africa was assessed by examining variation at seven microsatellite loci and a mitochondrial locus, cytochrome oxidase (COI). Mean COI diversity within populations was 0.63 ± 0.33 and 0.81 taken over all populations. Diversities averaged over microsatellite loci were high (mean number of alleles/locus ≥7.4; mean H E ≥ 65%) in all populations. Diversities averaged across populations were greater in East Africa (mean number of alleles = 22 ± 2.6; mean h e = 0.773 ± 0.033) than in southern Africa (mean number of alleles = 18.7 ± 4.0; mean h e = 0.713 ± 0.072). Differentiation among all populations was highly significant (R ST = 0.25, F ST = 0.132). Nei’s G ij statistics were 0.09 and 0.19 within regions for microsatellites and mitochondria, respectively; between regions, G ij was 0.14 for microsatellites and 0.23 for mitochondria. G ST among populations was 0.23 for microsatellite loci and 0.40 for mitochondria. The F, G and R statistics indicate highly restricted gene flow among G. m. morsitans populations separated over geographic scales of 12–917 km

Gut Microbiota, Probiotics and Diabetes

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes

Electrochemical detection of hybridization using peptide nucleic acids and methylene blue on self-assembled alkanethiol monolayer modified gold electrodes

WOS: 000178699100013An electrochemical hybridization biosensor based on peptide nucleic acid (PNA) probes is presented. PNA probes were attached covalently through a competition of free amines on the guanine bases and also at the 5' end of the probe, using N-(3-dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) onto a carboxylate terminated alkanethiol self-assembled monolayer (SAM) preformed on a gold electrode (AuE). The covalently immobilized probe could selectively hybridize with the target DNA to form a hybrid on the surface despite thebases being attached to the SAM. The changes in the peak currents of methylene blue (3,7-bis(dimethylamino)phenothiazin-5-ium chloride, MB), an electroactive label, were observed upon hybridization of probe with the target. Effective discrimination against point mutation was also obtained. Performance characteristics of the sensor are described, along with future prospects. (C) 2002 Elsevier Science B.V. All rights reserved