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

Soft, comfortable polymer dry electrodes for high quality ECG and EEG recording

Conventional gel electrodes are widely used for biopotential measurements, despite important drawbacks such as skin irritation, long set-up time and uncomfortable removal. Recently introduced dry electrodes with rigid metal pins overcome most of these problems; however, their rigidity causes discomfort and pain. This paper presents dry electrodes offering high user comfort, since they are fabricated from EPDM rubber containing various additives for optimum conductivity, flexibility and ease of fabrication. The electrode impedance is measured on phantoms and human skin. After optimization of the polymer composition, the skin-electrode impedance is only similar to 10 times larger than that of gel electrodes. Therefore, these electrodes are directly capable of recording strong biopotential signals such as ECG while for low-amplitude signals such as EEG, the electrodes need to be coupled with an active circuit. EEG recordings using active polymer electrodes connected to a clinical EEG system show very promising results: alpha waves can be clearly observed when subjects close their eyes, and correlation and coherence analyses reveal high similarity between dry and gel electrode signals. Moreover, all subjects reported that our polymer electrodes did not cause discomfort. Hence, the polymer-based dry electrodes are promising alternatives to either rigid dry electrodes or conventional gel electrodes

Vesicle coat proteins: Finding the missing link

The discovery of an ancient protein complex reveals the evolutionary relationships between the proteins that help to form vesicles

Evolution of educational inequalities in life and health expectancies at 25 years in Belgium between 2001 and 2011 : a census-based study

Background: Reducing socio-economic health inequalities is a public health priority, necessitating careful monitoring that should take into account changes in the population composition. We analyzed the evolution of educational inequalities in life expectancy and disability-free life expectancy at age 25 (LE25 and DFLE25) in Belgium between 2001 and 2011. Methods: The 2001 and 2011 census data were linked with the national register data for a five-year mortality follow up. Disability prevalence estimates from the health interview surveys (2001 to 2013) were used to compute DFLE according to Sullivan's method. LE25 and DFLE25 were computed by educational level (EL). Absolute differentials of LE25 and DFLE25 were calculated for each EL and for each period, as well as composite inequality indices (CII) of population-level impact of inequality. Changes over the 10-year period were then calculated for each inequality index. Results: The LE25 increased in all ELs and both genders, except in the lowest EL for women. The increase was larger in the highest EL, leading in 2011 to 6.07 and 4.58 years for the low-versus-high LE25 gaps respectively in men and women, compared to 5.19 and 3.76 in 2001, namely 17 and 22% increases. The upwards shift of the EL distribution led to a limited 7% increase of the CII among men but no change in women. The substantial increase of the DFLE25 in males with high EL (+4.5 years) and the decrease of the DFLE25 in women with low EL, results in a substantial increase of all considered DFLE25 inequality measures in both genders. In 2011, DFLE25 gaps were respectively 10.4 and 13.5 years in males and females compared to 6.51 and 9.30 in 2001, representing increases of 61 and 44% for the gaps, and 72 and 20% for the CII. Conclusion: The LE25 increased in all ELs, but at a higher pace in highly educated, leading to an increase in the LE25 gaps in both genders. After accounting for the upwards shift of the educational distribution, the population-level inequality index increased only for men. The DFLE25 increased only in highly educated men, and decreased in low educated women, leading to large increases of inequalities in both genders. A general plan to tackle health inequality should be set up, with particular efforts to improve the health of the low educated 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

Educational inequalities in premature mortality by region in the Belgian population in the 2000s

Background: In Belgium, socio-economic inequalities in mortality have long been described at country-level. As Belgium is a federal state with many responsibilities in health policies being transferred to the regional levels, regional breakdown of health indicators is becoming increasingly relevant for policy-makers, as a tool for planning and evaluation. We analyzed the educational disparities by region for all-cause and cause-specific premature mortality in the Belgian population. Methods: Residents with Belgian nationality at birth registered in the census 2001 aged 25-64 were included, and followed up for 10 years though a linkage with the cause-of-death database. The role of 3 socio-economic variables (education, employment and housing) in explaining the regional mortality difference was explored through a Poisson regression. Age-standardised mortality rates (ASMRs) by educational level (EL), rate differences (RD), rate ratios (RR), and population attributable fractions (PAF) were computed in the 3 regions of Belgium and compared with pairwise regional ratios. The global PAFs were also decomposed into the main causes of death. Results: Regional health gaps are observed within each EL, with ASMRs in Brussels and Wallonia exceeding those of Flanders by about 50% in males and 40% in females among Belgian. Individual SE variables only explained up to half of the regional differences. Educational inequalities were also larger in Brussels and Wallonia than in Flanders, with RDs ratios reaching 1.8 and 1.6 for Brussels versus Flanders, and Wallonia versus Flanders respectively; regional ratios in relative inequalities (RRs and PAFs) were smaller. This pattern was observed for all-cause and most specific causes of premature mortality. Ranking the cause-specific PAFs revealed a higher health impact of inequalities in causes combining high mortality rate and relative inequality, with lung cancer and ischemic heart disease on top for all regions and both sexes. The ranking showed few regional differences. Conclusions: For the first time in Belgium, educational inequalities were studied by region. Among the Belgian, educational inequalities were higher in Brussels, followed by Wallonia and Flanders. The region-specific PAF decomposition, leading to a ranking of causes according to their population-level impact on overall inequality, is useful for regional policy-making processes

EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy

Visual inspection of the EEG to determine the seizure onset zone (SOZ) in the context of the presurgical evaluation in epilepsy is time-consuming and often challenging or impossible. We offer an approach that uses EEG source imaging (ESI) in combination with functional connectivity analysis (FC) to localize the SOZ from ictal EEG. Ictal low-density-scalp EEG from 111 seizures in 27 patients who were rendered-seizure free after surgery was analyzed. For every seizure, ESI (LORETA) was applied on an artifact-free epoch selected around the seizure onset. Additionally, FC was applied on the reconstructed sources. We estimated the SOZ in two ways: (i)the source with highest power after ESI and (ii)the source with the most outgoing connections after ESI and FC. For both approaches, the distance between the estimated SOZ and the resected zone (RZ) of the patient were calculated. Using ESI alone, the SOZ was estimated inside the RZ in 31% of the seizures and within 10mm from the border of the RZ in 42%. For 18.5% of the patients, all seizures were estimated within 10mm of the RZ. Using ESI and FC, 72% of the seizures were estimated inside the RZ, and 94% within 10mm. For 85% of the patients, all seizures were estimated within 10mm of the RZ. FC provided a significant added value to ESI alone (p<0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy

Promising perspectives for ruminal protection of polyunsaturated fatty acids through polyphenol-oxidase-mediated crosslinking of interfacial protein in emulsions

Previously, polyunsaturated fatty acids (PUFA) from linseed oil were effectively protected (>80%) against biohydrogenation through polyphenol-oxidase-mediated protein crosslinking of an emulsion, prepared with polyphenol oxidase (PPO) extract from potato tuber peelings. However, until now, emulsions of only 2 wt% oil have been successfully protected, which implies serious limitations both from a research perspective (e.g. in vivo trials) as well as for further upscaling toward practical applications. Therefore, the aim of this study was to increase the oil/PPO ratio. In the original protocol, the PPO extract served both an emulsifying function as well as a crosslinking function. Here, it was first evaluated whether alternative protein sources could replace the emulsifying function of the PPO extract, with addition of PPO extract and 4-methylcatechol (4MC) to induce crosslinking after emulsion preparation. This approach was then further used to evaluate protection of emulsions with higher oil content. Five candidate emulsifiers (soy glycinin, gelatin, whey protein isolate (WPI), bovine serum albumin and sodium caseinate) were used to prepare 10 wt% oil emulsions, which were diluted five times (w/w) with PPO extract (experiment 1). As a positive control, 2 wt% oil emulsions were prepared directly with PPO extract according to the original protocol. Further, emulsions of 2, 4, 6, 8 and 10 wt% oil were prepared, with 80 wt% PPO extract (experiment 2), or with 90, 80, 70, 60 and 50 wt% PPO extract, respectively (experiment 3) starting from WPI-stabilized emulsions. Enzymatic crosslinking was induced by 24-h incubation with 4MC. Ruminal protection efficiency was evaluated by 24-h in vitro batch simulation of the rumen metabolism. In experiment 1, protection efficiencies were equal or higher than the control (85.5% to 92.5% v. 81.3%). In both experiments 2 and 3, high protection efficiencies (>80%) were achieved, except for emulsions containing 10 wt% oil emulsions (<50% protection), which showed oiling-off after enzymatic crosslinking. This study demonstrated that alternative emulsifier proteins can be used in combination with PPO extract to protect emulsified PUFA-rich oils against ruminal biohydrogenation. By applying the new protocol, 6.5 times less PPO extract was required