Ontregeling van moleculair gedrag : recente ontwikkelingen binnen de neuropsychofarmacologie

Rede uitgesproken bij de aanvaarding van het bijzondere lectoraat in de moleculaire farmacologie van biogene amnnen, vanwege de Stichting Fonds Medische Faculteit Rotterdam gevestigd bij de Erasmus Universiteit te Rotterdam op-woensdag 2 oktober 197

Changes in serine metabolism by a serum factor present in a group of episodic psychotic patients

__Abstract__ Addition of serum, obtained from patients suffering from an acute psychosis characterized by dysperceptions, to the culture media of fibroblasts altered the amino acid metabolism in these cells. After subculturing of fibroblasts in the presence of serum obtained from these patients, the concentrations of both serine and methionine were decreased in the medium as well as in the fibroblasts. Moreover, the concentration of taurine in the fibroblasts was increased. The specific activities of serine hydroxymethyltransferase and cystathionine β-synthase were also measured in the fibroblasts. It was found that both enzyme activities were significantly higher after subculturing with patients' serum as compared with serum obtained from healthy controls. It is concluded that a factor, present in the serum of these acute psychotic patients, is responsible for the observed changes in serine, taurine, and methionine concentrations in the fibroblasts as well as for the increased enzyme activities mentioned

Empowerment of personal injury victims through the internet: design of a randomized controlled trial

Abstract Background Research has shown that current claims settlement process can have a negative impact on psychological and physical recovery of personal injury (PI) victims. One of the explanations for the negative impact on health is that the claims settlement process is a stressful experience and victims suffer from renewed victimization caused by the claims settlement process. PI victims can experience a lack of information, lack of involvement, lack of 'voice', and poor communication. We present the first study that aims to empower PI victims with respect to the negative impact of the claims settlement process by means of an internet intervention. Methods/design The study is a two armed, randomized controlled trial (RCT), in which 170 PI victims are randomized to either the intervention or control group. The intervention group will get access to a website providing 1) an information module, so participants learn what is happening and what to expect during the claims settlement process, and 2) an e-coach module, so participants learn to cope with problems they experience during the claims settlement process. The control group will get access to a website with hyperlinks to commonly available information only. Participants will be recruited via a PI claims settlement office. Participants are included if they have been involved in a traffic accident which happened less than two years ago, and are at least 18 years old. The main study parameter is the increase of empowerment within the intervention group compared to the control group. Empowerment will be measured by the mastery scale and a self-efficacy scale. The secondary outcomes are perceived justice, burden, well being, work ability, knowledge, amount of damages, and lawyer-client communication. Data are collected at baseline (T0 measurement before randomization), at three months, six months, and twelve months after baseline. Analyses will be conducted according to the intention-to-treat principle. Discussion This study evaluates the effectiveness of an internet intervention aimed at empowerment of PI victims. The results will give more insight into the impact of compensation proceedings on health over time, and they can have important consequences for legal claims settlement. Strengths and limitations of this study are discussed. Trial registration Netherlands Trial Register NTR236

Teachers' perceptions and experiences of menstrual cycle education and support in UK schools

The purpose of this study was 2-fold, to (1) explore current education provision in UK schools including barriers to menstrual cycle education and (2) assess the perceived support teachers received to deliver menstrual cycle education. Seven hundred eighty-nine teachers (91% female) from all stages of school education in England (48%), Scotland (24%), Wales (22%) and Northern Ireland (6%) completed an online survey. The survey captured information on menstrual education in schools, teacher's knowledge and confidence of the menstrual cycle, support provided to teachers, provision of menstrual products in school and perceived impact of the menstrual cycle on young people in school. Four hundred ninety-eight teachers reported lessons were provided on the menstrual cycle (63%), predominantly delivered within personal, social, health and economic or science subjects, with over half of the lessons focusing on the biology (56%) or provision of menstrual products (40%) rather than lived experiences (14%). Teachers perceived the menstrual cycle affected participation in PE (88%), pupil confidence (88%), school attendance (82%) and attitude and behavior (82%). Overall, 80% of teachers felt receiving training would be beneficial to improve menstrual education. The results highlight education is scientifically focused, with less education on management of symptoms or lived experiences. Teachers also perceive the menstrual cycle to influence multiple aspects of school attendance and personal performance. There is a need to address menstrual education provided in schools across the UK to help empower girls to manage their menstrual cycle, preventing a negative impact on health and school performance

Design of a randomized controlled trial on the effects of Counseling of mental health problems by Occupational Physicians on return to work: the CO-OP-study

Mental health problems often lead to prolonged sick leave. In primary care, the usual approach towards these patients was the advice to take rest and not return to work before all complaints had disappeared. When complaints persist, these patients are often referred to psychologists from primary and specialized secondary care. As an alternative, ways have been sought to activate the Dutch occupational physician (OP) in primary care. Early 2000, the Dutch Association of Occupational Physicians (NVAB) published a guideline concerning the management by OPs of employees with mental health problems. The guideline received positive reactions from employees, employers and Dutch OPs. This manuscript describes the design of a study, which aims to assess the effects of the guideline, compared with usual care. In a randomized controlled trial (RCT), subjects in the intervention group were treated according to the guideline. The control group received usual care, with minimal involvement of the OP and easy access to a psychologist. Subjects were recruited from two Dutch police departments. The primary outcomes of the study are return to work and treatment satisfaction by the employee, employer, and OP. A secondary outcome is cost-effectiveness of the intervention, compared with usual care. Furthermore, prognostic measures are taken into account as potential confounders. A process evaluation will be done by means of performance indicators, based on the guideline. In this pragmatic trial, effectiveness instead of efficacy is studied. We will evaluate what is possible in real clinical practice, rather than under ideal circumstances. Many requirements for a high quality trial are being met. Results of this study will contribute to treatment options in occupational health practice for employees on sick leave due to mental health problems. Additionally, they may contribute to new and better-suited guidelines and stepped care. Results will become available during 2007. Current Controlled Trials ISRCTN3488734

The positive effect on determinants of physical activity of a tailored, general practice-based physical activity intervention

PACE (Physician-based Assessment and Counseling for Exercise) is an individualized theory-based minimal intervention strategy aimed at the enhancement of regular physical activity. The aim of this study was to evaluate the effectiveness of a PACE intervention applied by general practitioners (GPs) on potential determinants of physical activity. A randomized controlled trial was conducted in 29 general practices with the following inclusion criteria for patients: aged between 18 and 70 years, diagnosed with hypertension, hypercholesterolemia and/or non-insulin-dependent diabetes mellitus, and not in maintenance stage for regular physical activity. The intervention consisted of two visits with the GP and two telephone booster calls by a physical activity counselor. Determinants of physical activity were assessed with questionnaires at baseline, and at 8-week (short), 6-month (medium) and 1-year (long) follow-up. A significant positive effect was observed on self-efficacy, and on the use of cognitive and behavioral processes of change, at both short- and medium-term follow-up. The intervention respondents also perceived fewer barriers for regular physical activity at short-term and used behavioral processes of change more at long-term follow-up. No intervention effect was observed for perceived benefits of physical activity. In conclusion, this GP-based PACE intervention resulted in positive changes in potential determinants of physical activit

Endothelin receptors in the human coronary artery, ventricle and atrium - A quantitative autoradiographic analysis

In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1,3,11,15]ET-1. Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14±0.01 and 0.16±0.01, respectively) than in ventricular muscle (r.o.d.: 0.10±0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET 1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50): ET-1 (9.72±0.12) > BQ-123 (6.84±0.08) > [Ala1,3,11,15]ET-1 (6.40±0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I] Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03±0.25;[Ala1,3,11,15]ET-1, 8.40±0.14; low affinity pIC50: BQ-123, 7.24±0.14; [Ala1,3,11,15]ET-1, 6.99±0.09). These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle. In the human coronary artery, both radioligands labeled ETA binding sites, but [125I] Sf6b also labeled a non-ETA, non-ETB binding site with relatively high affinity for both BQ-123 and [Ala1,3,11,15] ET-1

Employment status and work-related problems of gastrointestinal cancer patients at diagnosis: a cross-sectional study

Objective To assess the employment status of patients with gastrointestinal cancer at diagnosis and to examine work-related problems of employed patients. Design New, consecutive patients were included at the Gastrointestinal Oncology Center Amsterdam, a one-stop, rapid access diagnostic assessment centre. Patients were interviewed on their employment status by a nurse. If (self-) employed, patients were asked to self-report on work-related problems, perceived distress (0-10), cancer-related problems, fatigue (MFI-20, range 4-20) and work ability (three WAI questions, range 0-10). Results Of all 333 included new consecutive patients (age range 32-89 years), 95 patients (28%) were (self-) employed at time of diagnosis, 179 (54%) were pensioners, and 59 were not working (18%). For the assessment of work-related problems, 45 (47%) of these 95 employed patients with cancer participated. Their mean age was 56 years, and patients had oesophageal/stomach (49%), colorectal (18%) or hepatic/pancreatic/biliary cancer (33%). Half of the employed patients (49%) were still at work, while 51% were on sick leave. The main reasons for sick leave were stress (35%), (scheduled) operation (26%), fatigue (17%) and pain (13%). Most patients on sick leave (70%) had no contact with their own occupational physician, although the majority (67%) would like to continue to work. Work-related problems were experienced by 73% of working patients. The mean work ability was 5.4, the mean general fatigue score was 11.5, and the mean distress score was 4.7. Employed patients on sick leave reported a lower work ability, more fatigue and higher distress but no more cancer-related problems compared with those still working. Conclusion A quarter of all patients with gastrointestinal cancer seen at an oncological centre are employed at time of diagnosis, and of these employed patients, 73% experience work-related problems. During diagnosis and treatment, information and support on work-related issues should be offered to patients with cancer as an essential part of high-quality oncological car

The prevalence and frequency of menstrual cycle symptoms are associated with women’s availability to train and compete: A study of 6,812 exercising women recruited using the STRAVA™ exercise app

Objectives: The menstrual cycle can affect sports participation and exercise performance. There are very few data on the specific menstrual cycle symptoms (symptoms during various phases of the cycle, not only during menstruation) experienced by exercising women. We aimed to characterise the most common symptoms; the number and frequency of symptoms; and we evaluated whether menstrual cycle symptoms were associated with sporting outcomes. Methods: 6,812 adult women of reproductive age (mean age: 38.3 (8.7) years) who were not using combined hormonal contraception were recruited via the STRAVA exercise app user database and completed a 39-part survey. Respondents were from seven geographical areas, and questions were translated and localised to each region (Brazil, n=1,288; France, n=1,911; Germany, n=1,178; Spain, n=1,204; UK & Ireland, n=2,311; and USA, n=2,479). The survey captured exercise behaviours; current menstrual status; the presence and frequency of menstrual cycle symptoms; medication use for symptoms; perceived effects of the menstrual cycle on exercise and work behaviours; and history of hormonal contraception use. We propose a novel Menstrual Symptom index (MSi) based on the presence and frequency of 18 commonly reported symptoms (range 0-54 where 54 would be all 18 symptoms each occurring very frequently). Results: The most prevalent menstrual cycle symptoms were mood changes/anxiety (90.6%), tiredness/fatigue (86.2%), stomach cramps (84.2%), and breast pain/tenderness (83.1%). After controlling for BMI, training volume and age, the Menstrual Symptom Index was associated with a greater likelihood of missing or changing training (OR= 1.09 (CI: 1.08,1.10); p<0.05), missing a sporting event/competition (OR= 1.07 (CI: 1.06,1.08); p=<0.05), absenteeism from work/academia (OR= 1.08 (CI: 1.07,1.09); p=<0.05), and use of pain medication (OR= 1.09 (CI: 1.08,1.09); p=<0.05). Conclusion: Menstrual cycle symptoms are very common in exercising women and women report that these symptoms compromise their exercise participation and work capacity. The Menstrual Symptom Index needs to be formally validated (psychometrics); at present it provides an easy way to quantify the frequency of menstrual cycle symptoms

The development and initial validation of the Health and Reproductive Survey (HeRS).

Due to the diversity in profiles associated with the female reproductive cycle and their potential physiological and psychological effects, monitoring the reproductive status of exercising females is important from a practical and research perspective. Moreover, as physical activity can influence menstrual function, the effects of physical activity energy expenditure on reproductive function should also be considered. The aim of this study was to develop and establish initial face and content validity of the Health and Reproductive Survey (HeRS) for physically active females, which is a retrospective assessment of menstrual function from menarche (first menstruation) to menopause (cessation of menstruation). Face validity was evaluated qualitatively, and the initial content validity was established through a principal component analysis. The face validity process was completed by 26 females aged 19-67 years and the content validity was established through a survey sent to a convenience sample of 392 females, of which 230 females (57.9% and aged 18-49 years) completed the survey. The revisions made following the face validation improved the understanding, flow, and coherence of the survey. The principal component analysis indicated that, at a minimum, the survey measures these constructs: menstrual cessation and associated moderators, athletic participation and performance levels (as associated with menstruation change and the menstrual cycle), age and menstrual cessation, hormonal contraception ("birth control"), and menarche and associated moderators. The Health and Reproductive Survey (HeRS) is a partially validated tool that can be used by researchers to characterize the menstrual status of physically active females relative to their physical activity status