DEcrease STress through RESilience training for Students (DESTRESS) Study: Protocol for a randomized controlled trial nested in a longitudinal observational cohort study.

INTRODUCTION: Chronic stress and burnout are highly prevalent among academically trained healthcare professionals, negatively affecting their well-being and capacity to engage in their work. Resilience to stress develops early in one's career path, hence offering resilience training to university students in these professions is one approach to fostering well-being and mental health. The aim of this study is to assess whether offering mindfulness-based resilience training to university students in healthcare professions reduces their perceived chronic stress. METHODS AND ANALYSIS: The study has a hybrid design combining a longitudinal observational cohort with a nested randomized controlled trial (RCT) with sequential multiple assignment and multistage adaptive interventions while taking participants' preferences into account. All students in healthcare related programmes at the Erasmus University Rotterdam are invited to participate. Within the observational cohort, students with a score of 14 or higher on the Perceived Stress Scale (PSS) are invited to take part in the RCT (n = 706). Eligible participants are randomized to control or active intervention in a ratio of 1:6. Those randomized to the control group and non-randomized participants in the cohort receive passive web-based psychoeducation about chronic stress and burnout through referral to specific websites. Participants randomized to the intervention group receive one of 8 active mindfulness-based interventions. They select a rank order of 4 preferred interventions and are randomized across these with equal probability. Non-response to the intervention is followed by sequential randomized assignment to another intervention, for a total maximum of 3 sequential interventions. All participants receive questionnaires at baseline, before and after each 8-week intervention period, and at 1- and 2-year follow-up. The primary outcome is perceived chronic stress measured with the PSS. Secondary outcomes include mental well-being, burnout, quality of life, healthcare utilization, drug use, bodyweight, mental and physical stress-related symptoms, resilience, and study progress. ETHICS AND REGISTRATION: Approval from the Medical Ethics Review Committee was obtained under protocol number MEC-2018-1645. The trial is registered in the Netherlands National Trial Register by registration number NL7623, 22/03/2019, https://www.trialregister.nl/.

Spatio-temporal Analysis of Multichannel Atrial Electrograms Based on a Concept of Active Areas.

Atrial tachycardia and atrial flutter are frequent arrhythmia that occur spontaneously and after ablation of atrial fibrillation. Depolarization waves that differ significantly from sinus rhythm propagate across the atria with high frequency (typically 140 to 220 beats per minute). A detailed and personalized analysis of the spread of depolarization is imperative for a successful ablation therapy. Thus, catheters with several electrodes are employed to measure multichannel electrograms inside the atria. Here we propose a new concept for spatio-temporal analysis of multichannel electrograms during atrial tachycardia and atrial flutter. It is based on the calculation of simultaneously active areas. The method allows to identify atrial tachycardia and to automatically distinguish between subtypes of focal activity, micro-reentry and macro-reentry.

Home haemodialysis in the Netherlands: State of the art.

Home haemodialysis (HHD) has gained popularity in recent years, due to improved clinical outcomes associated with frequent or prolonged haemodialysis sessions, best achievable at home. However, several barriers to HHD are perceived by the physician and patient, among which lack of experience and education, logistic difficulties and reimbursement issues seem to be the most important ones. HHD, in particular when performed with intensified frequency or duration, is associated with improved quality of life, blood pressure control and survival. Serious adverse events are rare; however, more vascular access complications arise due to frequent needling. This emphasises the importance of comprehensive education and training. This review aims to provide the physician with a detailed state of the art overview on HHD in the Netherlands, discussing potential barriers and benefits, and offering practical advice.

The long-term risk of recognized and unrecognized myocardial infarction for depression in older men.

BACKGROUND: The association between myocardial infarction (MI) and depression is well described. Yet, the underlying mechanisms are unclear and the contribution of psychological factors is uncertain. We aimed to determine the risk of recognized (RMI) and unrecognized (UMI) myocardial infections on depression, as both have a similar impact on cardiovascular health but differ in psychological epiphenomena. METHOD: Participants of the Rotterdam Study, 1823 men aged ⩾55 years, were followed for the occurrence of depression. RMI and UMI were ascertained using electrocardiography and medical history at baseline. We determined the strength of the association of RMI and UMI with mortality, and we studied the relationship of RMI and UMI with depressive symptoms and the occurrence of major depression. RESULTS: The risk of mortality was similar in men with RMI [adjusted hazard ratio (aHR) 1.71, 95% confidence interval (CI) 1.45-2.03] and UMI (aHR 1.58, 95% CI 1.27-1.97). Men with RMI had on average [unstandardized regression coefficient (B) 1.14, 95% CI 0.07-2.21] higher scores for depressive symptoms. By contrast, we found no clear association between UMI and depressive symptoms (B 0.55, 95% CI -0.51 to 1.62) in men. Analysis including occurrence of major depression as the outcome were consistent with the pattern of association. CONCLUSION: The discrepant association of RMI and UMI with mortality compared to depression suggests that the psychological burden of having experienced an MI contributes to the long-term risk of depression.

Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. METHODS: This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses. RESULTS: Higher white matter lesion volume (B = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. CONCLUSIONS: White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.

[Relationship between pre-dialysis period and mortality and morbidity; the importance of timely pre-dialysis care]. / Relatie predialyseduur met mortaliteit en morbiditeit; het belang van een tijdige voorbereiding op dialyse.

OBJECTIVE: To investigate if the duration of pre-dialysis nephrology care is a predictive factor for mortality and morbidity in the first year of renal replacement therapy (RRT). DESIGN: Cohort study. METHOD: We included all patients with chronic or acute-on-chronic renal failure whose estimated glomerular filtration time (eGFR) was < 30 ml/min/1.73 m2 6 months before starting RRT and in whom RRT was initiated in 2005-2006 or 2009-2010. Depending on the duration of the pre-dialysis period we allocated patients to the short (< 6 months) or the long (≥ 6 months) pre-dialysis group. Data regarding mortality and morbidity were registered at the initiation of RRT (T0), after 3 (T3), 6 (T6) and 12 (T12) months. RESULTS: Thirty-nine patients with a short pre-dialysis period and 49 patients with a long pre-dialysis period were included. Patients with a short pre-dialysis period had higher mortality (T6: 23.1% vs. 8.2%; p = 0.05), more hospital stays (2 vs. 1 stay; p = 0.02), and longer hospital stays (16 vs. 3 days; p < 0.01). Additionally, in this group RRT more often had to be started through an acute route of administration for dialysis, which was associated with a higher mortality at T6 (23.8% vs. 6.5%; p = 0.02). CONCLUSION: A too short pre-dialysis period is predictive for higher mortality and morbidity in the first year after initiation of RRT. The necessity for an acute route of administration for dialysis seems to be the most important predictor.

[How to approach the patient with supraventricular tachycardia in the EP lab: A systematic overview]. / Diagnostik bei supraventrikulären Tachykardien : Wie ist das Vorgehen im elektrophysiologischen Labor?

The term supraventricular tachycardia (SVT) summarizes those tachycardias involving the atrial myocardium along with the atrioventricular (AV) node. The prevalence is about 2.25 per 1000 (without atrial fibrillation and atrial flutter) and, therefore, SVT represents one of the most common group of arrhythmias besides atrial fibrillation encountered in the emergency department especially since they tend to recur until definite therapy. The clinical symptoms may include palpitations, anxiety, presyncope, angina, and dyspnea. Pharmacological therapy of these arrhythmias often fails. The present article deals with the differential diagnosis of SVT and also introduces a series of manuscripts that provide detailed insight into the differential diagnosis and treatment of these arrhythmias.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Gas exchange patterns of bumble bee foragers before and after exposing to lowered temperature.

The gas exchange patterns are known to vary between insect species, individuals and even intra-individually. Using volumetric-manometric and flow-through respirometry combined with IR-actography we studied how periods of low temperature affect the respiratory patterns of bumble bee Bombus terrestris foragers. We have shown, in this study, that there is a change in the respiratory patterns of individual B. terrestris foragers after exposing to low temperatures. The bumble bees seemed to become more inactive. The different respiratory patterns appeared in succession and the transition from one pattern to another was associated with the change from an active to a resting state. Typical patterns after exposition to low temperature were discontinuous gas exchange cycles (DGCs).

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

[Use of the NavX navigation system in ablation of atrial fibrillation]. / Einsatz des Navigationssystems NavX bei der Ablationsbehandlung von Vorhofflimmern.

Catheter ablation, notably the electric isolation of pulmonary veins, has become a well-established therapeutic approach in symptomatic atrial fibrillation. The NavX navigation system has been described to facilitate pulmonary vein isolation in patients with AF. EnSite NavX (Endocardial Solutions, St. Jude Medical, Inc., St. Paul, MN, USA) is a novel navigation system that measures the local voltage on every standard intra-cardiac electrode and calculates the electrode position in three-dimensional (3D) space. Any individual electrode of each catheter in 3D-space can be displayed and labelled individually. The geometry of any cardiac chamber can be reconstructed and additional information, e.g. electrical activation spreading, can be displayed colour coded on the surface. Recent studies investigating the possible advantages of this system in the ablation of persistent or paroxysmal atrial fibrillation are summarized. All reports showed a significant reduction in fluoroscopy and procedure time by the use of the NavX system compared to conventional fluoroscopic catheter guidance. This benefit can be obtained with simple visualisation of all intracardiac catheters alone or with additional reconstruction of the left atrium and pulmonary veins.

[Application of neural networks using the volume learning algorithm for the study of structure-activity relationship in chemical compounds]. / Primenenie neironnykh setei, ispol'zuiushchikh algoritm prostranstvennogo obucheniia dlia issledovaniia sviazei struktura-aktivnost' khimicheskikh soedinenii.

A volume learning algorithm for artificial neural networks was developed to quantitatively describe the three-dimensional structure-activity relationships using as an example N-benzylpiperidine derivatives. The new algorithm combines two types of neural networks, the Kohonen and the feed-forward artificial neural networks, which are used to analyze the input grid data generated by the comparative molecular field approach. Selection of the most informative parameters using the algorithm helped to reveal the most important spatial properties of the molecules, which affect their biological activities. Cluster regions determined using the new algorithm adequately predicted the activity of molecules from a control data set.

The influence of increasing dialysis treatment time and reducing dry weight on blood pressure control in hemodialysis patients: a prospective study.

A good blood pressure control can be achieved with long hemodialysis sessions (dialysis center of Tassin, France). However, it is not well known whether a higher dialysis dose or a lower dry weight is responsible for this phenomenon. In a preliminary study, 21 hypertensive dialysis patients, dialyzed three times a week for 3-5 h, were randomized into three groups during a 3-month study period. In 6 patients, the dialysis treatment time was increased by 2 h, and the dry weight was gradually decreased (group 1). In 7 patients the dialysis treatment time was increased by 2 h without a change in dry weight (group 2). In 8 patients the dry weight was gradually lowered without changing the dialysis treatment time (group 3). Before and after the study, cardiac index and left ventricular mass index (echocardiography) and forearm vascular resistance (strain gauge plethysmography) were determined on a middialytic day. The blood pressure was assessed by 48-hour ambulatory monitoring. The antihypertensive medication was reduced when the postdialytic blood pressure became <130/80 mm Hg. The dry weight was reduced by 2.6 +/- 1.4 kg in group 1 and by 2.3 +/- 0.8 kg in group 3 (p < 0.05). The number of classes of antihypertensive medication was reduced from 3.3 to 1.8 in group 1 (NS), from 2.4 to 1.7 in group 2 (NS), and from 3.1 to 1.3 in group 3 (p < 0.05). The dose of the remaining antihypertensive drugs was reduced by 50% in group 1 (p < 0.05), by 32% in group 2 (NS), and by 72.2% in group 3 (p < 0.05). The interdialytic systolic blood pressure decreased significantly after increasing the dialysis time without changing the dry weight (group 2: 7 +/- 5 mm Hg; p < 0.05). The systolic blood pressure was also lower in the other patients groups: group 1: 13 +/- 26 mm Hg, group 3 : 7 +/- 16 mm Hg (NS). The pulse pressure decreased significantly in group 2 (7 +/- 5 mm Hg; p < 0.05) and in group 3 (6 +/- 7 mm Hg; p < 0.05) and tended to decrease in group 1 (11 +/- 12 mm Hg; p = 0.08). The diastolic blood pressure and the day-night blood pressure difference did not change significantly, nor did cardiac index and left ventricular mass index. The forearm vascular resistance tended to decrease in the patients on long dialysis sessions. This preliminary study suggests that the dialysis treatment time might have an independent beneficial effect on blood pressure control.

Antennal sensilla of the ground beetle Platynus dorsalis (Pontoppidan, 1763) (Coleoptera, Carabidae).

The typology, number, and distribution pattern of antennal sensilla of the ground beetle Platynus dorsalis (Pontoppidan) (Coleoptera, Carabidae) were studied using scanning electron microscopy. The 4.3-4.6-mm-long filiform antennae of the beetles consist of the scape, pedicel, and nine flagellomeres. In both sexes, four subtypes of sensilla chaetica, five subtypes of sensilla basiconica, sensilla trichodea, two subtypes of sensilla campaniformia, sensilla auricillica, and sensilla coeloconica were distinguished. The possible function of the sensilla was discussed and three types of sensilla were considered as olfactory, sensilla trichodea and sensilla basiconica types 1 and 2. Olfactory sensilla form two separate, dorsal and ventral, fields of sensilla on the flagellomeres, which seems to be common in ground beetles. The total numbers of olfactory trichoid (approximately 1,000 hairs) and basiconic sensilla type 1 (1,700-1,800 pegs) on the antennae of P. dorsalis are 5-7 times higher than on the antennae of the ground beetle Bembidion lampros, suggesting that nocturnally active P. dorsalis is much more sensitive to odours perceived by these sensilla than B. lampros with diurnal activity and hunting predominantly by sight. No remarkable sexual differences in the types, numbers, and distribution of antennal sensilla were found in P. dorsalis.

Conformation changes of albumin in its interaction with physiologically active compounds as studied by quasi-elastic light scattering spectroscopy and ultrasonic method.

The effect of pH and binding of ten physiologically active compounds (PAC) on conformational organization of human serum albumin (HSA) in aqueous solutions has been studied using two different methods. The hydrodynamic sizes of albumin globule and its subunits were obtained from diffusion coefficients measured by quasi-elastic light scattering. The adiabatic volume compressibility of albumin was evaluated from ultrasonic velocity and density measurements. It was found, that albumin globule has the most compact configuration (hydrodynamic diameter 59-62 A and molar compressibility 5.6 m(3) Pa(-1) mol(-1)) at physiological pH 7.4. The changes in pH, both increase to 8.0 and decrease to 5.4, result in the growth of globule size to 68-81 A. An additional peak corresponding to diffusion of the separate albumin subdomains (hydrodynamic diameter 32-40 A) is observed in the light scattering spectra and globule compressibility decrease to 4.5-2.8 m(3) Pa(-1) mol(-1) at the acidic shift of pH. The additional peak was not displayed and globule compressibility increased to 6.4 m(3) Pa(-1) mol(-1) at the basic shift of pH. The acidic changes were attributed to unfolded and elastic conformation of albumin with a high motility of separate subdomains, whilst the basic changes correspond to a closed compressible configuration of albumin molecule. The interaction with propranolol, clonidine, phenylephrine, carbachol and tripeptide fMLP, which hinder adenylate cyclase (AdC) and activate Ca-polyphosphoinisitide (Ca-PPI) signaling system of a cell, initiates structural rearrangements similar to acidic transitions of albumin. Isoproterenol, yohimbine, diphenhydramine, chlorpromazine and atropine, which activate AdC and hinder Ca-PPI, cause conformational changes of albumin similar to basic transitions. The results obtained are consistent with the idea of structural and pharmacological similarity among the drugs inside the marked groups.

[Topological similarity of antagonist binding sites in biogenic amine receptors]. / Topologicheskoe podobie uchastkov sviazyvaniia antagonistov v retseptorakh biogennykh aminov.

The influence of physical and chemical properties of some sites of transmembrane receptor domains on the receptors ability to interact with nonspecific antagonists was investigated mathematically. The properties of sites located in 3rd and 7th transmembrane domains are most likely to explain pharmacological characteristics of the receptors. The possibility of receptor blocking by nonspecific antagonists not by competing with agonists but by influencing the receptor conformation is discussed.