Comparing the effectiveness of two cardiovascular prevention programmes for highly educated professionals in general practice : a randomised clinical trial

Background: Cardiovascular disease is a major cause of mortality and morbidity and its prevalence is set to increase. While the benefits of medical and lifestyle interventions are established, the effectiveness of interventions which seek to improve the way preventive care is delivered in general practice is less so. The aim was to study and to compare the effectiveness of 2 intervention programmes for reducing cardiovascular risk factors within general practice. Methods: A randomised controlled trial was conducted in Belgium between 2007-2010 with 314 highly educated and mainly healthy professionals allocated to a medical (MP) or a medical + lifestyle (MLP) programme. The MP consisted of medical assessments (screening and follow-up) and the MLP added a tailored lifestyle change programme (web-based and individual coaching) to the MP. Primary outcomes were total cholesterol, blood pressure, and body mass index (BMI). The secondary outcomes were smoking status, fitness-score, and total cardiovascular risk. Results: The mean age was 41 years, 95 (32%) participants were female, 7 had a personal cardiovascular event in their medical history and 3 had diabetes. There were no significant differences found between MP and MLP in primary or secondary outcomes. In both study conditions decreases of cholesterol, systolic blood pressure, and diastolic blood pressure were found. Unfavourable increases were found for BMI (p < .05). A significant decrease of the overall cardiovascular risk was reported (p < .001). Conclusions: Both interventions are effective in reducing cardiovascular risk. In our population the combined medical and lifestyle programme was not superior to the medical programme

Prediction of the Effect of Adaptation and Active HB Mechanics on Prestin-Based Amplification Using a Macroscopic Model of the Cochlea

Introduction: Negative social evaluation is associated with psychopathology. Given the frequency of evaluation through increasingly prevalent virtual social networks, increased understanding of the effects of this social evaluation is urgently required. Methods: A new digital social peer evaluation experiment (digi-SPEE) was developed to mimic everyday online social interactions between peers. Participants received mildly negative feedback on their appearance, intelligence, and congeniality. Two hundred and forty-one young people [58.9% female, aged 18.9 years (15 to 34)] from an ongoing novel general population twin study participated in this study. Positive affect (PA), negative affect (NA), implicit self-esteem, and cortisol were assessed before and after exposure to the social evaluation experiment. Results: The social evaluation experiment decreased PA (B=-5.25, p Conclusion: The digi-SPEE represents a social evaluation stressor that elicits biological and implicit and explicit mental changes that are relevant to mechanisms of psychopathology

Psychiatric Diagnosis Revisited:Towards a System of Staging and Profiling Combining Nomothetic and Idiographic Parameters of Momentary Mental States

BACKGROUND: Mental disorders may be reducible to sets of symptoms, connected through systems of causal relations. A clinical staging model predicts that in earlier stages of illness, symptom expression is both non-specific and diffuse. With illness progression, more specific syndromes emerge. This paper addressed the hypothesis that connection strength and connection variability between mental states differ in the hypothesized direction across different stages of psychopathology. METHODS: In a general population sample of female siblings (mostly twins), the Experience Sampling Method was used to collect repeated measures of three momentary mental states (positive affect, negative affect and paranoia). Staging was operationalized across four levels of increasing severity of psychopathology, based on the total score of the Symptom Check List. Multilevel random regression was used to calculate inter- and intra-mental state connection strength and connection variability over time by modelling each momentary mental state at t as a function of the three momentary states at t-1, and by examining moderation by SCL-severity. RESULTS: Mental states impacted dynamically on each other over time, in interaction with SCL-severity groups. Thus, SCL-90 severity groups were characterized by progressively greater inter- and intra-mental state connection strength, and greater inter- and intra-mental state connection variability. CONCLUSION: Diagnosis in psychiatry can be described as stages of growing dynamic causal impact of mental states over time. This system achieves a mode of psychiatric diagnosis that combines nomothetic (group-based classification across stages) and idiographic (individual-specific psychopathological profiles) components of psychopathology at the level of momentary mental states impacting on each other over time

Cortisol dynamics in depression:Application of a continuous-time process model

Background: The temporal dynamics of cortisol may be altered in depression. Optimally studying these dynamics in daily life requires specific analytical methods. We used a continuous-time multilevel process model to study set point (rhythm-corrected mean), variability around this set point, and regulation strength (speed with which cortisol levels regulate back to the set point after any perturbation). We examined the generalizability of the parameters across two data sets with different sampling and assay methods, and the hypothesis that regulation strength, but not set point or variability thereof, would be altered in depressed, compared to non-depressed individuals. Methods: The first data set is a general population sample of female twins (n = 523), of which 21 were depressed, with saliva samples collected 10 times a day for 5 days. The second data set consists of pair-matched clinically depressed and non-depressed individuals (n = 30), who collected saliva samples 3 times a day for 30 days. Set point, regulation strength and variability were examined using a Bayesian multilevel Ornstein-Uhlenbeck (OU) process model. They were first compared between samples, and thereafter assessed within samples in relation to depression. Results: Set point and variability of salivary cortisol were twice as high in the female twin sample, compared to the pair-matched sample. The ratio between set point and variability, as well as regulation strength, which are relative measures and therefore less affected by the specific assay method, were similar across samples. The average regulation strength was high; after an increase in cortisol, cortisol levels would decrease by 63 % after 10 min, and by 95 % after 30 min, but depressed individuals of the pair-matched sample displayed an even faster regulation strength. Conclusions: The relative parameters of the two data sets. The results suggest that regulation strength is increased in depressed individuals. We recommend the presented methodology for future studies and call for replications with more diverse depressed populations

Unraveling the Role of Loneliness in Depression:The Relationship Between Daily Life Experience and Behavior

Objective: Focusing on temporal associations between momentary (or state) loneliness, appraisal of social company, and being alone in daily life may help elucidate mechanisms that contribute to the development of prolonged (or trait) loneliness and major depressive disorder (MDD). We aim to examine if (a) a self-reinforcing loop between loneliness, negative appraisals of social company, and being alone in daily life may contribute to trait loneliness; (b) this possible self-reinforcing loop may also contribute to the development of MDD, by testing differences in temporal relationships between these social elements in participants who did or did not develop MDD during follow-up; and (c) any of these social elements at baseline predicted a MDD at follow-up. Methods: A female general population sample (n = 417) participated in an experience sampling method (ESM) study. Time-lagged analyses between loneliness, appraisal of social company, and being alone were examined at baseline, and their associations with the development of MDD during 20 months follow-up were investigated. Results: State loneliness was followed by an increase in negative appraisals of social company and a higher frequency of being alone. Further, negative appraisals of social company were associated with a higher frequency of being alone afterward. Only the latter was significant in the transition to MDD group. Trait loneliness predicted MDD during follow-up. Conclusions: Avoiding social contact after appraising company more negatively may contribute to the development of MDD.</p

Fed-batch fermentation of GM-CSF-producing glycoengineered Pichia pastoris under controlled specific growth rate

<p>Abstract</p> <p>Background</p> <p>Yeast expression systems with altered N-glycosylation are now available to produce glycoproteins with homogenous, defined N-glycans. However, data on the behaviour of these strains in high cell density cultivation are scarce.</p> <p>Results</p> <p>Here, we report on cultivations under controlled specific growth rate of a GlycoSwitch-Man5 <it>Pichia pastoris </it>strain producing Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) at high levels (hundreds of milligrams per liter). We demonstrate that homogenous Man₅GlcNAc₂N-glycosylation of the secreted proteins is achieved at all specific growth rates tested.</p> <p>Conclusions</p> <p>Together, these data illustrate that the GlycoSwitch-Man5 <it>P. pastoris </it>is a robust production strain for homogenously N-glycosylated proteins.</p

FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain

Multiple lines of evidence suggest that fatty acids (FA) play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF) and FA desaturase (FADS) genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193) and mice (93) and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03). Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Throug

Stress reactivity links childhood trauma exposure to an admixture of depressive, anxiety, and psychosis symptoms

Childhood trauma exposure has been associated with a clinically relevant mixed phenotype of psychopathology composed of depressive, anxiety, and psychosis symptoms, across healthy and clinical samples. Altered stress-reactivity after exposure to childhood trauma may be a plausible underlying mechanism explaining this association. In a general population sample of female twins (T0=564; T1=483), associations between childhood trauma exposure and symptom profile (no symptoms, isolated symptoms, or a mixed phenotype) on the one hand, and daily life stress reactivity on the other were investigated. Daily life stress reactivity was measured using the Experience Sampling Method (ESM), and was defined as negative affect reactivity to minor daily life stressors. Individuals exposed to childhood trauma who reported a mixed phenotype of psychopathology showed a significant increase in emotional reactivity to daily life stress (activity and social stress), compared with trauma-exposed individuals without a mixed phenotype. In the trauma-exposed mixed phenotype group, increased emotional reactivity to event-stress predicted more severe symptoms at ±14 month follow-up. This study found evidence that may link heightened emotional reactivity to stress in individuals with a trauma history to the risk for later comorbid psychopathology