Independent associations between sedentary time, moderate-to-vigorous physical activity, cardiorespiratory fitness and cardio-metabolic health : a cross-sectional study

We aimed to study the independent associations of sedentary time (ST), moderate-to-vigorous physical activity (MVPA), and objectively measured cardiorespiratory fitness (CRF) with clustered cardio-metabolic risk and its individual components (waist circumference, fasting glucose, HDL-cholesterol, triglycerides and blood pressure). We also investigated whether any associations between MVPA or ST and clustered cardio-metabolic risk were mediated by CRF. MVPA, ST, CRF and individual cardio-metabolic components were measured in a population-based sample of 341 adults (age 53.8 +/- 8.9 years; 61% men) between 2012 and 2014. MVPA and ST were measured with the SenseWear pro 3 Armband and CRF was measured with a maximal exercise test. Multiple linear regression models and the product of coefficients method were used to examine independent associations and mediation effects, respectively. Results showed that low MVPA and low CRF were associated with a higher clustered cardio-metabolic risk (beta = -0.26 and beta = -0.43, both p<0.001, respectively). CRF explained 73% of the variance in the association between MVPA and clustered cardio-metabolic risk and attenuated this association to non-significance. After mutual adjustment for MVPA and ST, CRF was the most important risk factor for a higher clustered cardio-metabolic risk (beta = -0.39, p<0.001). In conclusion, because of the mediating role of CRF, lifestyle-interventions need to be feasible yet challenging enough to lead to increases in CRF to improve someone's cardio-metabolic health

LC-MS characterization and cell-binding properties of chelate modified somatropin

Somatropin, a recombinant protein containing 191 amino acids, is derived from the endogenous human growth hormone, somatotropin. This protein is clinically used in children and adults with inadequate endogenous growth hormone to stimulate a normal bone and muscle growth. In addition, somatropin is recently being investigated for the diagnosis and radiotherapy of certain hormonal cancers. In some of these cancers, over-expression of the human growth hormone receptor (hGHR) is described. The modification of the protein with a chelating agent like NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) allows the inclusion of metals coupled to the protein. The NOTA unit is selectively introduced on a lysine side chain. As site-specific labelling is necessary to avoid active region interactions (1-16, 41-68, 103-119 and 167-175), characterization of the chelate-modified somatropin is indispensable. Therefore, we have applied an enzymatic digestion procedure using trypsin, chymotrypsin and a combination of both enzymes. The resulting peptides were then monitored using HPLC-MSn, allowing the investigation of the exact amino acid modifications. The use of a mixture of trypsin and chymotrypsin gave an enhanced information efficiency. Moreover, the intact protein, without enzymatic degradation, was analysed on a protein HPLC column using UV detection for quantification and ESI-MS/MS for characterization. Based upon the HPLC-MSn results of the digested somatropin, the chelating molecule is mainly bound to a specific lysine amino acid that is located away from the receptor binding site. Therefore, the cell-binding functionality of the characterized NOTA-somatropin is measured, using a HepG2 cell line

Longitudinal study on the association between three dietary indices, anthropometric parameters and blood lipids

Background: From a health promotion perspective, the use of dietary indices is preferred above single nutrients and foods to evaluate diet quality. Longitudinal research about the association between dietary indices and respectively anthropometric parameters and blood lipids is lacking. The aim of this study was to investigate the longitudinal association between three dietary indices (Healthy Eating Index-2010 (HEI), Mediterranean Diet Score (MDS) and Diet Quality Index (DQI)) and respectively anthropometric parameters and blood lipids. Methods: A three day diet record was completed by 373 men and 197 women in 2002-2004 and 2012-2014. HEI, MDS and DQI were calculated. Waist circumference (WC) and Body Mass Index (BMI) were used as anthropometric parameters. A linear regression analysis was performed to investigate associations between changes in dietary indices and changes in respectively anthropometric parameters and blood lipids, adjusted for potential confounders. Results: Only in men an increase in all three dietary indices was associated with a decrease in WC and BMI in the non-adjusted analysis and for HEI and DQI also in the adjusted analysis. No longitudinal associations were found between dietary indices and blood lipids both in men and women. Conclusions: Only few associations were found between dietary indices and anthropometric parameters, whilst no associations were found with blood lipids. An increase in dietary indices was associated with an improvement in anthropometric parameters only in men. As this is the first study investigating associations between changes in dietary indices and changes in respectively anthropometric parameters and blood lipids, further research is needed to evaluate these possible associations

Transcutaneous vagus nerve stimulation does not affect verbal memory performance in healthy volunteers

Introduction: Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy. Recent studies with transcutaneous VNS (tVNS) have also shown positive effects on various subdomains of cognitive functioning in healthy volunteers. In this randomized, controlled, crossover study, we investigated the effect of tVNS on a word recognition memory paradigm in healthy volunteers to further investigate the potential of tVNS in the treatment of cognitive disorders. Methods: We included 41 healthy participants aged between 18 and 30 years (young age group) and 24 healthy participants aged between 45 and 80 years (older age group). Each participant completed a word recognition memory paradigm during three different conditions: true tVNS, sham, and control. During true tVNS, stimulation was delivered at the cymba conchae. Sham stimulation was delivered by stimulating the earlobe. In the control condition, no stimulation was given. In each condition, participants were asked to remember highlighted words from three test paragraphs. Accuracy scores were calculated for immediate recall after each test paragraph and for delayed recognition at the end of the paradigm. We hypothesized that highlighted words from paragraphs in the true tVNS condition would be more accurately recalled and/or recognized compared to highlighted words from paragraphs in the sham or control condition. Results: In this randomized study, tVNS did not affect the accuracy scores for immediate recall or delayed recognition in both age groups. The younger group showed significantly higher accuracy scores than the older group. The accuracy scores improved over time, and the most recently learned words were better recognized. Participants rated true tVNS as significantly more painful; however, pain was not found to affect accuracy scores. Conclusion: In this study, tVNS did not affect verbal memory performance in healthy volunteers. Our results could not replicate the positive effects of invasive VNS on word recognition memory in epilepsy patients. Future research with the aim of improving cognitive function should focus on the rational identification of optimized and individualized stimulation settings primarily in patients with cognitive deficits

Longitudinal study on the association between cardiorespiratory fitness, anthropometric parameters and blood lipids

Background: Longitudinal evidence concerning the association between cardiorespiratory fitness (CRF) and blood lipids and between anthropometric parameters (ANTP) and blood lipids is limited. This study aimed to investigate the association between changes in CRF and ANTP and changes in blood lipids. Methods: In 2002-2004 and 2012-2014,652 participants were tested. CRF was measured as VO(2)peak using a maximal ergometer test. Waist circumference (WC) and Body Mass Index (BMI) were used as ANTP. Blood samples were analyzed for total cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides. A linear regression analysis was performed to investigate associations between changes in CRF and ANTP and changes in blood lipids. Results: After adjustment a decrease in CRF was associated with an increase in triglycerides and a decrease in HDL cholesterol in men. An increase in WC was associated with an increase in TC, LDL cholesterol and ratio total/HDL cholesterol and a decrease in HDL cholesterol, while an increase in BMI was associated with an increase in ratio total/HDL cholesterol and a decrease in HDL cholesterol. Conclusions: WC and BMI were more longitudinally associated with blood lipids compared with CRF. Improving ANTP can enhance the blood lipid profile, while CRF had only limited influence

Ten-year change in sedentary behaviour, moderate-to-vigorous physical activity, cardiorespiratory fitness and cardiometabolic risk : independent associations and mediation analysis

BACKGROUND: We aimed to study the independent associations of 10-year change in sedentary behaviour (SB), moderate-to-vigorous physical activity (MVPA) and objectively measured cardiorespiratory fitness (CRF), with concurrent change in clustered cardiometabolic risk and its individual components (waist circumference, fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides and blood pressure). We also determined whether associations were mediated by change in CRF (for SB and MVPA), waist circumference (for SB, MVPA and CRF) and dietary intake (for SB). METHODS: A population-based sample of 425 adults (age (mean±SD) 55.83±9.40; 65% men) was followed prospectively for 9.62±0.52 years. Participants self-reported SB and MVPA and performed a maximal cycle ergometer test to estimate peak oxygen uptake at baseline (2002-2004) and follow-up (2012-2014). Multiple linear regression and the product of coefficients method were used to examine independent associations and mediation effects, respectively. RESULTS: Greater increase in SB was associated with more detrimental change in clustered cardiometabolic risk, waist circumference, HDL cholesterol and triglycerides, independently of change in MVPA. Greater decrease in MVPA was associated with greater decrease in HDL cholesterol and increase in clustered cardiometabolic risk, waist circumference and fasting glucose, independent of change in SB. Greater decrease in CRF was associated with more detrimental change in clustered cardiometabolic risk and all individual components. Change in CRF mediated the associations of change in SB and MVPA with change in clustered cardiometabolic risk, waist circumference and, only for MVPA, HDL cholesterol. Change in waist circumference mediated the associations between change in CRF and change in clustered cardiometabolic risk, fasting glucose, HDL cholesterol and triglycerides. CONCLUSIONS: A combination of decreasing SB and increasing MVPA, resulting in positive change in CRF, is likely to be most beneficial towards cardiometabolic health

Low 10-year reproducibility of glycaemic index and glycaemic load in a prospective cohort study

When relating glycaemic index (GI) and glycaemic load (GL) to health outcomes, many prospective cohort studies assess the nutritional exposure only once in time, that is, at the start of the study, presuming a stability in nutritional consumption during the course of the study. The aim of this study is to investigate the reproducibility of GI and GL. This is a prospective cohort study in which 562 middle-aged Belgian adults noted all foods and drinks consumed during 3d in 2002 and 2012. GI and GL were calculated after reference tables. The Pearson correlation coefficients between 2002 and 2012 were 0.27 for GI and 0.41 for GL. For GF 33 % of the participants remained in the same quintile between 2002 and 2012, whereas 31 % moved lo a non-adjacent quintile. For GL. this was 34 and 28%, respectively. The lowest and the highest quintiles of GI were the most stable, with 40 and 44 % of the participants staying in the same quintile. This was only 22 % for the fourth quintile. The same tendency was present for GL - that is, the most extreme quintiles were the most stable. This study shows 10-year correlation coefficients for GI and GL below 0.50. Multiple nutritional assessments and limiting the analysis to the extreme quintiles of GI and GL will limit a possible misclassification in the prospective cohort studies owing to the low reproducibility

Cross-sectional study on the relationship between the Mediterranean Diet Score and blood lipids

Background: Blood lipids are cardiovascular health indicators. High LDL cholesterol values and/or high total cholesterol (TC)/HDL cholesterol ratios are positively related with cardiovascular mortality. Evidence suggests that a Mediterranean diet can reduce the incidence of cardiovascular diseases. Adherence to the Mediterranean diet is often measured by the Mediterranean Diet Score (MDS). However, the association between the Mediterranean diet and blood lipid profiles seems still inconclusive. The aim of this study was to investigate the relationship between the MDS, its different components and blood lipid profiles. Methods: A sample of 506 women and 707 men (aged 18-75 years) was recruited. Three-day diet records were used to calculate the MDS. Blood samples were analyzed for serum TC, LDL and HDL cholesterol. ANOVA was used to analyze blood lipids across the MDS tertiles. A multivariate linear regression analysis was performed to investigate the associations between the MDS, its components and blood lipids, adjusted for several confounders. All analyses were stratified by gender. Results: Few gender-specific associations were found between the MDS, its components and blood lipids. Only in men, the total MDS was negatively related with LDL cholesterol and the ratio TC/HDL cholesterol while positively with HDL cholesterol. In women, respectively two (MUFA/SFA and cereals) and in men three (fruits & nuts, meat and alcohol) of the nine MDS components were related with blood lipids. Conclusions: Analyses investigating the relationship between the MDS, its components and blood lipid profiles indicate only limited influence of the Mediterranean diet on blood lipids. More associations were detected in men compared to women

Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders

Background and purpose In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. Methods In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (>= 50% reduction in seizure frequency) and non-responders. Results Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). Conclusion Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network