Health of greenspace workers: Morbidity and mortality data from the AGRICAN cohort.

INTRODUCTION: Knowledge on the health of greenspace workers is scarce, even though they are exposed to many occupational hazards. The aim of this study was to analyze mortality by cause, prevalence of some non-cancer diseases, and incidence of the main cancers among greenspace workers. METHODS: A sub-cohort of greenspace workers was formed within the AGRICAN cohort. Demographic information, health characteristics and self-reported diseases at enrollment were described separately in terms of frequencies (%), median and Interquartile Range (IQR) for greenspace workers, farmers, and other non-agricultural workers. Causes of death and cancer incidence were identified through linkage with cancer registries from enrollment (2005-2007) to 2015. Hazard ratio (HR) and 95% Confidence Intervals [95% CI] were estimated using Cox proportional hazard regression with age as the underlying timescale. RESULTS: The sub-cohort included 6247 greenspace workers who were higher proportion men, younger and more frequently smokers than farmers and non-agricultural workers. Male and female greenspace workers reported more history of allergic diseases; and males, more history of depression. Compared to other workers male greenspace workers showed a non-significant higher mortality from ischemic cardiological diseases (HR = 1.14 [0.81-1.60]). Incidence was higher in male greenspace workers than farmers for overall cancer (HR = 1.15 [1.04-1.27]), cancer of the prostate (HR = 1.21 [1.02-1.44]), thyroid (HR = 2.84 [1.26-6.41]), testis (HR = 3.98 [1.50-10.58]) and skin melanoma (HR = 2.15 [1.33-3.47]). Non-significant increased risks were also found for sarcomas, larynx and breast. In women, risk of breast cancer was higher in greenspace workers than in farmers (HR = 1.71 [1.17-2.50]). CONCLUSIONS: Whereas greenspace workers have often been included with other pesticide applicators in epidemiological studies, our analyses highlighted the differences between these two populations. They demonstrate the need to study them separately and to investigate more thoroughly the role of specific occupational exposures such as pesticides as well as the effect on women.

Occupational pesticide exposure, cancer and chronic neurological disorders: A systematic review of epidemiological studies in greenspace workers.

CONTEXT: The greenspace sector includes a broad range of occupations: gardeners, landscapers, municipal workers, maintenance operators of public facilities, golf-course employees and other sports facilities, horticulturists, plant and tree nursery workers etc. The health impact of occupational pesticide exposure has mainly been studied among farmers. Other professionals such as greenspace workers are also extremely exposed, presenting specific exposure features (practices, types of pesticide used). The aim of this review was to summarize epidemiological literature that examine the relationship between pesticide exposure and the risk of cancer and long-term health effects in greenspace workers. METHOD: Six main groups of greenspace workers were identified and examined through a systematic literature review based on PubMed and Scopus. The studies were then grouped according to their design, health outcomes and the type of population studied. RESULTS: Forty-four articles were selected among the 1679 identified. Fifteen studies were conducted exclusively among greenspace workers, while ten also studied these workers with other pesticide applicators. Six were cohorts from the general population in which greenspace workers were identified. Elevated risks were found in several studies for leukaemia, soft-tissue sarcoma, multiple myeloma, non-Hodgkin lymphoma and Parkinson's disease. DISCUSSION: The majority of studies used rough parameters for defining exposure such as job titles which could lead to the misclassification of exposure, with the risk of false or positive negative conclusions. Health outcomes were mainly collected through registries or death certificates, and information regarding potential confounders was often missing. CONCLUSION: The review identified only 15 studies conducted exclusively among greenspace workers. Elevated risk was found for several sites of cancer and Parkinson's diseases. Further epidemiological research is needed, conducted specifically on these workers, to better characterize this population, its exposure to pesticides and the related health effects.

Breast magnetic resonance elastography: a review of clinical work and future perspectives.

This review on magnetic resonance elastography (MRE) of the breast provides an overview of available literature and describes current developments in the field of breast MRE, including new transducer technology for data acquisition and multi-frequency-derived power-law behaviour of tissue. Moreover, we discuss the future potential of breast MRE, which goes beyond its original application as an additional tool in differentiating benign from malignant breast lesions. These areas of ongoing and future research include MRE for pre-operative tumour delineation, staging, monitoring and predicting response to treatment, as well as prediction of the metastatic potential of primary tumours.

Pesticide exposure in greenspaces: Comparing field measurement of dermal contamination with values predicted by registration models.

Since 2014, the Agricultural Operator Exposure Model (AOEM) has been the harmonised European model used for estimating non-dietary operator exposure to pesticide. It is based on studies conducted by the pesticide companies and it features 13 different crops including non-agricultural areas such as amenity grasslands. The objective of this study was to compare the dermal exposure measured during a field study conducted in a non-agricultural area with the corresponding values estimated by the model AOEM. The non-controlled field study was conducted in France in 2011 and included 24 private and public gardeners who apply glyphosate with knapsack sprayers. Dermal exposure was measured using the whole-body method and cotton gloves. Each measured value had an estimated value given by AOEM and we tested their correlation using linear regression. The model overestimated body exposure for all observations and there was no correlation between values. However, it underestimated hand exposure by 42 times and it systematically underestimated the exposure when the operators were wearing gloves, especially during the application. The model failed at being conservative regarding hand exposure and highly overestimated the protection afforded by the gloves. At a time of glyphosate renewed approval in Europe, non-controlled field studies conducted by academics are needed to improve AOEM model, especially in the non-agricultural sector. Indeed, among the 34 studies included in the model, none were conducted on a non-agricultural area and only four assessed the exposure when using a knapsack sprayer. Moreover, knapsack sprayers being the main equipment used worldwide in both agricultural and non-agricultural settings, it is also crucial to integrate new data specific to this equipment in the model. Operator exposure should be estimated with accuracy in the registration process of pesticides to ensure proper safety as well as in epidemiological studies to improve exposure assessment.

Case-based e-learning to improve the attitude of medical students towards occupational health, a randomised controlled trial.

OBJECTIVES: Undergraduate medical teaching in occupational health (OH) is a challenge in universities around the world. Case-based e-learning with an attractive clinical context could improve the attitude of medical students towards OH. The study question is whether case-based e-learning for medical students is more effective in improving knowledge, satisfaction and a positive attitude towards OH than non-case-based textbook learning. METHODS: Participants, 141 second year medical students, were randomised to either case-based e-learning or text-based learning. Outcome measures were knowledge, satisfaction and attitude towards OH, measured at baseline, directly after the intervention, after 1 week and at 3-month follow-up. RESULTS: Of the 141 participants, 130 (92%) completed the questionnaires at short-term follow-up and 41 (29%) at 3-month follow-up. At short-term follow-up, intervention and control groups did not show a significant difference in knowledge nor satisfaction but attitude towards OH was significantly more negative in the intervention group (F=4.041, p=0.047). At 3-month follow-up, there were no significant differences between intervention and control groups for knowledge, satisfaction and attitude. CONCLUSIONS: We found a significant decrease in favourable attitude during the internship in the experimental group compared with the control group. There were no significant differences in knowledge or satisfaction between case-based e-learning and text-based learning. The attitude towards OH should be further investigated as an outcome of educational programmes.

Early signaling, referral, and treatment of adolescent chronic pain: a study protocol.

BACKGROUND: Chronic pain is prevalent among young people and negatively influences their quality of life. Furthermore, chronic pain in adolescence may persist into adulthood. Therefore, it is important early on to promote the self-management skills of adolescents with chronic pain by improving signaling, referral, and treatment of these youngsters. In this study protocol we describe the designs of two complementary studies: a signaling study and an intervention study. METHODS AND DESIGN: The signaling study evaluates the Pain Barometer, a self-assessed signaling instrument for chronic pain in adolescents. To evaluate the feasibility of the Pain Barometer, the experiences of youth-health care nurses will be evaluated in semi-structured interviews. Also, we will explore the frequencies of referral per health-care provider. The intervention study evaluates Move It Now, a guided self-help intervention via the Internet for teenagers with chronic pain. This intervention uses cognitive behavioural techniques, including relaxation exercises and positive thinking. The objective of the intervention is to improve the ability of adolescents to cope with pain. The efficacy of Move It Now will be examined in a randomized controlled trial, in which 60 adolescents will be randomly assigned to an experimental condition or a waiting list control condition. DISCUSSION: If the Pain Barometer is proven to be feasible and Move It Now appears to be efficacious, a health care pathway can be created to provide the best tailored treatment promptly to adolescents with chronic pain. Move It Now can be easily implemented throughout the Netherlands, as the intervention is Internet based. TRIAL REGISTRATION: Dutch Trial Register NTR1926.

The responsiveness of quality of life utilities to change in depression: a comparison of instruments (SF-6D, EQ-5D, and DFD).

BACKGROUND: Utilities are often a main outcome parameter in economic evaluations. Because depression has a large influence on quality of life, it is expected that utilities are responsive to changes in depression. OBJECTIVE: To evaluate the change in utility derived from different instruments in depression, including the Short Form 6D (SF-6D), the Euroqol based on the UK (EQ-5D(UK)), the Euroqol based on the Dutch tariff (EQ-5D(NL)), and utilities derived from Beck Depression Inventory Second Edition (BDI-II) using the Depression-Free-Day method. METHOD: This study evaluated the responsiveness, the minimally important difference, and the agreement in utility change derived from the different instruments. RESULTS: The SF-6D, EQ-5D(UK), and EQ-5D(NL) were responsive. The minimally important difference values are in line with previous studies, about 0.3. The Depression-Free-Day method nearly always resulted in positive utility changes, even for subgroups that had no change or deterioration in health status or depression. There was poor agreement between utility changes of the SF-6D, EQ-5D (either EQ-5D(UK) or EQ-5D(NL)), and DFDu. CONCLUSIONS: The SF-6D, EQ-5D(UK), and EQ-5D(NL) seem responsive and thus adequate for estimating utility in depression treatment. We do not recommend the use of the Depression-Fee-Day method. The low agreement between utility changes indicates that outcomes of the different instruments are incomparable.

Economic evaluation of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial.

BACKGROUND: Evidence about the cost-effectiveness and cost utility of computerised cognitive-behavioural therapy (CCBT) is still limited. Recently, we compared the clinical effectiveness of unsupported, online CCBT with treatment as usual (TAU) and a combination of CCBT and TAU (CCBT plus TAU) for depression. The study is registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236). AIMS: To assess the cost-effectiveness of CCBT compared with TAU and CCBT plus TAU. METHOD: Costs, depression severity and quality of life were measured for 12 months. Cost-effectiveness and cost-utility analyses were performed from a societal perspective. Uncertainty was dealt with by bootstrap replications and sensitivity analyses. RESULTS: Costs were lowest for the CCBT group. There are no significant group differences in effectiveness or quality of life. Cost-utility and cost-effectiveness analyses tend to be in favour of CCBT. CONCLUSIONS: On balance, CCBT constitutes the most efficient treatment strategy, although all treatments showed low adherence rates and modest improvements in depression and quality of life.

Does the weather make us sad? Meteorological determinants of mood and depression in the general population.

It is a common and well-spread belief that people feel more depressed when the weather is bad. However, whether meteorological factors such as temperature, sunshine and rainfall can actually account for variations in the prevalence of depression in the general population has yet to be investigated. We aimed to assess the influence of weather conditions on the seasonal variation of depression observed in the general population. We used data from a large-scale depression-screening programme in the south of the Netherlands. Seasonal prevalence of DSM-IV classified major depression and sad mood in a sample of 14,478 participants from the general population was calculated, and linked to mean daily temperature, duration of sunshine and duration of rainfall in logistic regression analyses. The prevalence of major depression and sad mood showed seasonal variation, with peaks in the summer and fall. Weather conditions were not associated with mood, and did not explain the seasonal variation we found. We conclude that, contrary to popular belief, weather conditions and sad mood or depression do not seem to be associated. Future studies might use daily measures of well-being as outcome.

Minor and major depression in the general population: does dysfunctional thinking play a role?

BACKGROUND: Although most research suggests that minor depression is part of a depression continuum, conflicting results have also been found. Moreover, little is known about dysfunctional thinking in minor depression and how this varies along the continuum. Especially, research on the form of dysfunctional thinking (ie, extreme responding) is lacking. We have addressed these issues by reporting results from a large community sample. METHODS: Demographic, clinical, and cognitive factors (ie, content and form of dysfunctional thinking) were compared between minor depression (ie, 2-4 symptoms), major depression with 5 to 6 symptoms, and major depression with 7 to 9 symptoms. A large community sample (N = 1129) was used. Differences between the 3 subgroups were examined as well as linear relations between number of symptoms and factors marking the severity. RESULTS: Most demographic variables did not distinguish the 3 depression status categories from each other. Clinical and cognitive factors acted in synchrony with the depression continuum. CONCLUSIONS: Minor depression should be considered as part of continuum together with major depression. Not only the content but also the form of dysfunctional thinking seems to play a major role in depression. Extreme positive responding is more prominent in mild depression, whereas more severely depressed individuals have a general tendency toward extreme negative responding. This finding, if replicated, may have important implications for the cognitive theory of depression.

Clinical effectiveness of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial.

BACKGROUND: Computerised cognitive-behavioural therapy (CCBT) might offer a solution to the current undertreatment of depression. AIMS: To determine the clinical effectiveness of online, unsupported CCBT for depression in primary care. METHOD: Three hundred and three people with depression were randomly allocated to one of three groups: Colour Your Life; treatment as usual (TAU) by a general practitioner; or Colour Your Life and TAU combined. Colour Your Life is an online, multimedia, interactive CCBT programme. No assistance was offered. We had a 6-month follow-up period. RESULTS: No significant differences in outcome between the three interventions were found in the intention-to-treat and per protocol analyses. CONCLUSIONS: Online, unsupported CCBT did not outperform usual care, and the combination of both did not have additional effects. Decrease in depressive symptoms in people with moderate to severe depression was moderate in all three interventions. Online CCBT without support is not beneficial for all individuals with depression.

[Introducing the diagnostic inventory for depression in the Netherlands]. / Introductie van de Diagnostic Inventory for Depression in Nederland.

BACKGROUND: The Diagnostic Inventory for Depression (did) is a new self-report questionnaire based on the dsm-iv inclusion criteria for a major depressive disorder. AIM: To analyse the Dutch translation of the did and examine the psychometric properties of the inventory. methods We conducted a large-scale internet-based screening among the general population. results Reliability, convergent validity and factor structure were good. The did-nl may classify participants accurately. CONCLUSION: The results look promising and the did-nl can give added value to existing questionnaires. However, since the classification potential has not yet been sufficiently demonstrated, a clinical interview will still be needed.

Clinical and cost-effectiveness of computerised cognitive behavioural therapy for depression in primary care: design of a randomised trial.

BACKGROUND: Major depression is a common mental health problem in the general population, associated with a substantial impact on quality of life and societal costs. However, many depressed patients in primary care do not receive the care they need. Reason for this is that pharmacotherapy is only effective in severely depressed patients and psychological treatments in primary care are scarce and costly. A more feasible treatment in primary care might be computerised cognitive behavioural therapy. This can be a self-help computer program based on the principles of cognitive behavioural therapy. Although previous studies suggest that computerised cognitive behavioural therapy is effective, more research is necessary. Therefore, the objective of the current study is to evaluate the (cost-) effectiveness of online computerised cognitive behavioural therapy for depression in primary care. METHODS/DESIGN: In a randomised trial we will compare (a) computerised cognitive behavioural therapy with (b) treatment as usual by a GP, and (c) computerised cognitive behavioural therapy in combination with usual GP care. Three hundred mild to moderately depressed patients (aged 18-65) will be recruited in the general population by means of a large-scale Internet-based screening (N = 200,000). Patients will be randomly allocated to one of the three treatment groups. Primary outcome measure of the clinical evaluation is the severity of depression. Other outcomes include psychological distress, social functioning, and dysfunctional beliefs. The economic evaluation will be performed from a societal perspective, in which all costs will be related to clinical effectiveness and health-related quality of life. All outcome assessments will take place on the Internet at baseline, two, three, six, nine, and twelve months. Costs are measured on a monthly basis. A time horizon of one year will be used without long-term extrapolation of either costs or quality of life. DISCUSSION: Although computerised cognitive behavioural therapy is a promising treatment for depression in primary care, more research is needed. The effectiveness of online computerised cognitive behavioural therapy without support remains to be evaluated as well as the effects of computerised cognitive behavioural therapy in combination with usual GP care. Economic evaluation is also needed. Methodological strengths and weaknesses are discussed. TRIAL REGISTRATION: The study has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236).

A new MR-compatible loading device to study in vivo muscle damage development in rats due to compressive loading.

To study the aetiology of pressure ulcers an MR-compatible loading device was developed. Magnetic resonance imaging provides the possibility of non-invasive evaluation of muscle tissue after compressive loading. Pressure was applied to the tibialis anterior region of rats by means of an indenter. The developed MR-compatible loading device allowed high quality consecutive MR measurements for up to 6h. Tissue was evaluated both during and after loading. Two loading protocols were used; a large indentation of 4.5mm (mean pressure 150 kPa) was applied for 2h and a small indentation of 2.9 mm (mean pressure 50 kPa) was applied for 4h. T2-weighted MR images after the large indentation showed an immediate increase in signal intensity, associated with damage, following load removal. After 20 h the signal intensity remained higher in the affected regions. Afterwards the tissue was perfusion fixated for histological examination. Histological evaluation revealed an inflammatory response and severe muscle necrosis. No signal increase was observed after small indentation. With this new set-up, the different factors that may play a role in the onset of muscle damage can be studied, what we believe will lead to a better understanding of the contributing factors to pressure ulcer development.

Role for oxygen radicals in self-sustained HIV-1 replication in monocyte-derived macrophages: enhanced HIV-1 replication by N-acetyl-L-cysteine.

N-acetyl-L-cysteine (NAC) has been proposed as a therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated T cells. However, NAC and glutathione enhanced acute HIV-1 replication in monocyte-derived macrophages. Buthionine sulfoximine did not affect NAC-mediated enhanced HIV-1 replication, indicating that the NAC-mediated effects are glutathione-independent. Superoxide dismutase and the hydroxyl radical scavengers dimethylthiourea and thiourea, but not urea, inhibited acute HIV-1 replication in macrophages. NAC reduced ferricytochrome c and increased dose-dependently Fe(III)-citrate and Fe(III)-EDTA-catalyzed hydroxyl radical formation in a system using glucose and glucose oxidase. Dimethylthiourea and thiourea, but not urea and superoxide dismutase, dose-dependently inhibited NAC-mediated enhancement of HIV-1 replication. These data suggest that oxygen radicals play an important role in self-sustained HIV-1 replication in macrophages and that oxygen radical scavengers other than NAC should be considered as therapeutic agents for AIDS patients.

N-acetyl-L-cysteine-induced up-regulation of HIV-1 gene expression in monocyte-derived macrophages correlates with increased NF-kappaB DNA binding activity.

Nuclear factor kappaB (NF-kappaB) is an important cellular regulator of human immunodeficiency virus (HIV) gene expression. In T cells, N-acetyl-L-cysteine (NAC) inhibits the induction of NF-kappaB and transcription of HIV-1. However, NAC up-regulates HIV-1 replication in monocyte-derived macrophages (MDM). In this study we demonstrate that NAC treatment of MDM transfected with a chloramphenicol acetyltransferase (CAT) construct under transcriptional control of the HIV-1 long terminal repeat resulted in an up-regulation of CAT activity. Furthermore, MDM transfected with a HIV-1-NF-kappaB-CAT construct also produced increased CAT activity after NAC treatment. In addition, electrophoretic mobility shift assays revealed that nuclei of NAC-treated MDM contained increased binding activity to wild-type, but not mutant, kappaB oligonucleotides. Components of the binding activity were identified with antibodies as the NF-kappaB subunits p50 and p65. These data indicate that NAC-induced enhancement of HIV-1 replication in MDM is regulated at the level of viral gene expression and mediated by NF-kappaB.

Antibodies and complement enhance binding and uptake of HIV-1 by human monocytes.

OBJECTIVE: To characterize antibody- and complement-mediated binding and uptake of HIV-1 by human monocytes. DESIGN: The first step in the infection of the monocyte by HIV-1 is binding of the virus to the susceptible cell. Procedures were designed to assess the influence of anti-HIV-1 antibodies and complement on this binding, and to study the process of internalization following binding. METHODS: Human monocytes were incubated with fluorescein-labelled purified HTLV-IIIB virions and human sera with high-titre anti-HIV-1 antibodies and/or complement. Binding and uptake of virus by the monocytes was measured as fluorescence per cell by flow cytometry. RESULTS: Binding of purified HIV-1 to monocytes was increased by complement and, to a lesser extent, by anti-HIV-1 antibodies. Uptake of HIV-1 bound to the monocyte appeared to be mediated by antibodies and was increased further by the presence of complement. Complement alone, however, resulted in the uptake of only a small part of the bound virus. CONCLUSIONS: Complement significantly increases the binding of HIV-1 to human monocytes, and a combination of antibodies and complement efficiently mediates uptake of HIV-1 by monocytes.

Characterisation and functional aspects of monoclonal antibodies specific for surface proteins of coagulase-negative staphylococci.

Mouse monoclonal antibodies (MAbs) raised against whole cells of Staphylococcus epidermidis strain 354 were characterised morphologically and functionally. Nine MAbs showed strong reactivity with coagulase-negative staphylococci (CNS). Only two MAbs were specific for CNS; both belonged to the IgG1 subclass, and one, MAb 36.4, reacted only with the strain used for immunisation. In immunoblotting, both CNS-specific MAbs 36.3 and 36.4 reacted strongly with cell-wall protein bands of 220 Kda of S.epidermidis strain 354 and weak reactivity was observed with a 110-Kda band. MAb 36.3 reacted also with 220-230 Kda bands of two other S.epidermidis strains (291 and ATCC 35984) and a 160-180 Kda band of S.epidermidis strain 354. Only MAb 36.4 promoted phagocytosis of strain 354 by polymorphonuclear leucocytes (PMNL) and monocytes, whereas MAb 36.3 and the other MAbs lacked this activity. Opsonisation of S. epidermidis with MAb 36.4 in the presence of complement enhanced uptake by PMNL, but not by monocytes. Furthermore, S.epidermidis strain 354 opsonised with MAb 36.4 induced chemiluminescence of PMNL. Immuno-gold electronmicroscopy with both MAbs 36.3 and 36.4 demonstrated a homogeneous distribution of gold particles on the surface as well as close to the surface of S.epidermidis.

Denaturation of proteins from a non-food perspective.

Controlled denaturation, or the prevention of denaturation, is an important aspect in the development of food applications of proteins. For the use of proteins in non-food applications such as surfactants, adhesives, coatings or plastics, it is discussed that a certain degree of denaturation must occur in order to make proteins processable, and to reach the required product properties such as strength, water resistance or adhesion. By adjusting the processing parameters (temperature, water content, chemicals) conditions can be created to allow structural changes in the protein. The effect of processing on some product properties will be discussed.

Two rapid complementary methods to detect progressive zidovudine resistance mutations in mononuclear cells of HIV-infected patients.

The objective of the study was to evaluate a rapid screening technique for the presence of mutations in the viral reverse transcriptase gene of HIV following prolonged therapy with zidovudine in patients with AIDS. Peripheral blood mononuclear cells (PBMCs) of 14 HIV-infected patients were analyzed by micro-titer point mutation assay (PMA) before therapy with zidovudine and after at least 10 months of treatment. In addition, five of these were analyzed longitudinally. Three nontreated HIV-seropositive individuals were tested as controls. To confirm the validity of the PMA, patients' material was also analyzed with the single strand conformational polymorphism (SSCP) assay. After 10-55 months of treatment, at codons 41, 70, and 215 a shift from predominantly wild type strains to a mixture of wild type and mutant strains (21%-100% mutant sequences) appeared in the majority of patients' PBMCs. At codons 67 and 219, the wild type strain persisted after therapy in all but 3 patients. Most mutations were detected by SSCP as well as by PMA, except for one mutation at codon 41 and one at codon 70. However, when the two mutations were both present, SSCP and PMA were both able to detect these mutations. In conclusion, both PMA and SSCP are rapid and simple methods for screening for mutations causing drug resistance in zidovudine-treated HIV-infected patients. Although PMA is more labor-extensive than SSCP, the advantage of PMA over SSCP is that it permits the quantitative detection of point mutations coding for zidovudine resistance. The application of these assays may improve procedures of monitoring and modifying antiretroviral therapy on an individual basis.