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To assess the effects of family nursing conversations on family caregiver burden, patients' quality of life, family functioning and the amount of professional home health care.A controlled before-and-after design.Intervention group families participated in two family nursing conversations incorporated in home health care; control group families received usual home health care. Patients and family members completed a set of questionnaires on entering the study and 6 months later to assess family caregiver burden, family functioning and patients' quality of life. The amount of home health care was extracted from patient files. Data were collected between January 2018-June 2019.Data of 51 patients (mean age 80; 47% male) and 61 family members (mean age 67; 38% male) were included in the results. Family caregiver burden remained stable in the intervention group whereas it increased in the control group. Family functioning improved significantly compared with the control group for patients and family members in the intervention group. No significant effects on patients' quality of life emerged. The amount of professional home health care decreased significantly in the intervention group whereas it remained equal in the control group.Family nursing conversations prevented family caregiver burden, improved family functioning, but did not affect patients' quality of life. In addition, the amount of home health care decreased following the family nursing conversations.Countries with ageing populations seek to reduce professional and residential care and therefore encourage family caregiving. Intensive family caregiving, however, places families at risk for caregiver burden which may lead to increased professional care and admission into residential care. This study demonstrates that family nursing conversations help nurses to prevent family caregiver burden and improve family functioning while decreasing the amount of home health care.目标: 探讨家庭护理交谈对家庭照料人员负担、患者生活质量、家庭功能及专业家庭保健服务量的影响。 设计: 前后对照研究。 方法: 干预组家庭在家庭护理服务中加入两次家庭护理交谈;对照组家庭接受常规的家庭护理服务。患者和家属在研究期间和6个月后完成一组问卷调查,以评估家庭照料人员的负担、家庭功能和患者生活质量。从患者档案中提取家庭护理服务量。收集2018年1月至2019年6月之间的数据。 结果: 结果中包含51名患者(平均年龄80岁;47%为男性)和61名家庭成员(平均年龄67岁;38%为男性)的数据。家庭照料人员的负担在干预组中保持稳定,但在对照组中呈现增长。与对照组相比,干预组患者和家庭成员的家庭功能明显改善。对患者生活质量无显著影响。在干预组中,专业家庭护理量显著减少,而在对照组中保持不变。 结论: 家庭护理交谈能避免造成家庭照料人员的负担,改进家庭功能,且不影响患者的生活质量。此外,家庭护理交谈后,家庭护理量有所减少。 影响: 人口老龄化国家寻求减少专业护理和住院护理,鼓励家庭护理。然而,密集的家庭护理使家庭照料人员面临负担增加的风险,可能导致专业护理和住院护理增加。本研究显示,家庭护理交谈有助于护士在减少家庭护理量的同时,减轻家庭照料人员的负担,以及改善家庭功能。.

This paper reports on the research methods used in five different projects aimed at supporting people living with dementia in their everyday lives and activities of daily living. In all five projects, people living with dementia and their informal carers were involved. Applied methods ranged from passive involvement in the form of observations to very active involvement consisting of consultation rounds and think-aloud sessions. The projects highlighted that people living with dementia can still contribute to the development of solutions that support them in the self-management of their symptoms and challenges, as well as technological solutions that support them in daily living. LinkedIn: https://www.linkedin.com/in/jvhoof1980/

Context: Only 55% of the athletes return to competitive sports after an anterior cruciate ligament (ACL) injury. Athletes younger than 25 years who return to sports have a second injury rate of 23%. There may be a mismatch between rehabilitation contents and the demands an athlete faces after returning to sports. Current return-to-sports (RTS) tests utilize closed and predictable motor skills; however, demands on the field are different. Neurocognitive functions are essential to manage dynamic sport situations and may fluctuate after peripheral injuries. Most RTS and rehabilitation paradigms appear to lack this aspect, which might be linked to increased risk of second injury. Objective: This systematic and scoping review aims to map existing evidence about neurocognitive and neurophysiological functions in athletes, which could be linked to ACL injury in an integrated fashion and bring an extensive perspective to assessment and rehabilitation approaches. Data Sources: PubMed and Cochrane databases were searched to identify relevant studies published between 2005 and 2020 using the keywords ACL, brain, cortical, neuroplasticity, cognitive, cognition, neurocognition, and athletes. Study Selection: Studies investigating either neurocognitive or neurophysiological functions in athletes and linking these to ACL injury regardless of their design and technique were included. Study Design: Systematic review. Level of Evidence: Level 3. Data Extraction: The demographic, temporal, neurological, and behavioral data revealing possible injury-related aspects were extracted and summarized. Results: A total of 16 studies were included in this review. Deficits in different neurocognitive domains and changes in neurophysiological functions could be a predisposing risk factor for, or a consequence caused by, ACL injuries. Conclusion: Clinicians should view ACL injuries not only as a musculoskeletal but also as a neural lesion with neurocognitive and neurophysiological aspects. Rehabilitation and RTS paradigms should consider these changes for assessment and interventions after injury.

To prevent overweight in children, regular physical activity is important. To stimulate childhood physical activity it seems relevant to consider motor skill competence stimulation in infants. Motor milestones can be seen as benchmarks of development in where motor coordination is central and may lead to more movement opportunities to increase physical activity. This study shows that infants who achieve their motor milestones later are physically less active and more sedentary when growing older. However, the effects are small. Although we found that infants reach their motor milestone later over the past decades, motor milestone achievement and BMI during childhood are largely independent. Instead of physical activity, aerobic fitness might have a stronger association with health outcomes during adolescence. Higher aerobic fitness reduced cardiometabolic risk in adolescents even in those with higher BMI. Therefore, stimulating high intensive physical activities to increase aerobic fitness is advised. Physical activity during childhood could be stimulated by focusing on early motor milestone achievement and by involving parents as a role-model for PA. For future studies, and comparability of studies, it would be good to have guidelines for the use and data processing of accelerometry data. Furthermore, we advise to combine accelerometry data with other measurements, like questionnaires to define the nature of the activities, and to measure aerobic fitness, because it may be more relevant for health outcomes than physical activity alone.

Background The prescription of physical activity (PA) in clinical care has been advocated worldwide. This “exercise is medicine” (E=M) concept can be used to prevent, manage, and cure various lifestyle-related chronic diseases. Due to several challenges, E=M is not yet routinely implemented in clinical care. Objective This paper describes the rationale and design of the Physicians Implement Exercise = Medicine (PIE=M) study, which aims to facilitate the implementation of E=M in hospital care. Methods PIE=M consists of 3 interrelated work packages. First, levels and determinants of PA in different patient and healthy populations will be investigated using existing cohort data. The current implementation status, facilitators, and barriers of E=M will also be investigated using a mixed-methods approach among clinicians of participating departments from 2 diverse university medical centers (both located in a city, but one serving an urban population and one serving a more rural population). Implementation strategies will be connected to these barriers and facilitators using a systematic implementation mapping approach. Second, a generic E=M tool will be developed that will provide tailored PA prescription and referral. Requirements for this tool will be investigated among clinicians and department managers. The tool will be developed using an iterative design process in which all stakeholders reflect on the design of the E=M tool. Third, we will pilot-implement the set of implementation strategies, including the E=M tool, to test its feasibility in routine care of clinicians in these 2 university medical centers. An extensive learning process evaluation will be performed among clinicians, department managers, lifestyle coaches, and patients using a mixed-methods design based on the RE-AIM framework. Results This project was approved and funded by the Dutch grant provider ZonMW in April 2018. The project started in September 2018 and continues until December 2020 (depending on the course of the COVID-19 crisis). All data from the first work package have been collected and analyzed and are expected to be published in 2021. Results of the second work package are described. The manuscript is expected to be published in 2021. The third work package is currently being conducted in clinical practice in 4 departments of 2 university medical hospitals among clinicians, lifestyle coaches, hospital managers, and patients. Results are expected to be published in 2021. Conclusions The PIE=M project addresses the potential of providing patients with PA advice to prevent and manage chronic disease, improve recovery, and enable healthy ageing by developing E=M implementation strategies, including an E=M tool, in routine clinical care. The PIE=M project will result in a blueprint of implementation strategies, including an E=M screening and referral tool, which aims to improve E=M referral by clinicians to improve patients’ health, while minimizing the burden on clinicians.

Background: Health care organizations supporting individuals with intellectual disabilities (IDs) carry out a range of interventions to support and improve a healthy lifestyle. However, it is difficult to implement an active and healthy lifestyle into daily support. The presence of numerous intervention components, multiple levels of influence, and the explicit use of theory are factors that are considered to be essential for implementation in practice. A comprehensive written lifestyle policy provides for sustainability of a lifestyle approach. It is unknown to what extent these crucial factors for successful implementation are taken into consideration by health care organizations supporting this population.Aim: To analyze the intervention components, levels of influence, explicit use of theory, and conditions for sustainability of currently used lifestyle interventions within lifestyle approaches aiming at physical activity and nutrition in health care organizations supporting people with ID.Methods: In this descriptive multiple case study of 9 health care organizations, qualitative data of the lifestyle approaches with accompanying interventions and their components were compiled with a newly developed online inventory form.Results: From 9 health care organizations, 59 interventions were included, of which 31% aimed to improve physical activity, 10% nutrition, and 59% a combination of both. Most (49%) interventions aimed at the educational component and less at daily (19%) and generic activities (16%) and the evaluation component (16%). Most interventions targeted individuals with ID and the professionals whereas social levels were underrepresented. Although 52% of the interventions were structurally embedded, only 10 of the 59 interventions were theory-driven.Conclusion: Health care organizations could improve their lifestyle approaches by using an explicit theoretical basis by expanding the current focus of the interventions that primarily concentrate on their clients and professionals toward also targeting the social and external environment as well as the introduction of a written lifestyle policy. This policy should encompass all interventions and should be the responsibility of those in the organization working with individuals with ID. In conclusion, comprehensive, integrated, and theory-driven approaches at multiple levels should be promoted.

Introduction: The primary aim was to investigate feasibility of a web-based cross-over Paleolithic diet intervention in the general population. The secondary aim was to calculate the sample size needed to reach a statistically significant difference in effect of a Paleolithic-like diet on psychological and somatic symptoms compared with the Dutch consensus diet.Methods: 35 participants from the general population were recruited using social media. Participants filled-out an intake questionnaire to assess representativeness of the sample. Participants were instructed to consume both a Paleolithic-like diet and the Dutch consensus diet during four weeks, the order was randomly assigned. After each period, participants filled-out a questionnaire to assess compliance to the dietary instructions, the Depression Anxiety Stress Scale to assess psychological symptoms and the Rosmalen Somatization Index to assess somatic symptoms.Results: It took 42 days to recruit 35 participants, the drop-out rate was 20% and compliance to the diets was at least 68%. Participants were representative of the general Dutch population regarding age, BMI, marital and work status and symptoms of depression and anxiety. Participants showed greater reductions in psychological and somatic symptoms when consuming a Paleolithic-like diet compared to the Dutch consensus diet. Sample size calculations showed that at least 30 participants need to be recruited for statistical significance.Conclusion: Conducting a web-based cross-over dietary intervention in the general population appeared feasible. Given the ease of increasing sample size in web-based studies, we recommend recruiting more participants than estimated when comparing a Paleolithic-like diet to the Dutch consensus diet.

With ageing of our population and the accompanying increase in the number of people living with dementia, it is important to find modifiable risk factors to postpone the onset of cognitive decline. Diet has been proposed such a modifiable risk factor. To date, numerous studies have been conducted demonstrating a possible role of specific nutrients and foods in cognitive functioning. However, as people do not consume single nutrients, the research field has shifted towards studying dietary patterns in which synergistic effects of single nutrients and/or foods can be studied. The main aim of this thesis was to study the association of healthful dietary patterns with cognitive functioning. In addition, nutrient intake inadequacies were assessed and the potential to change dietary intake in older adults aged 65 years and older was studied. Chapter 2 describes nutrient intake of 245 Dutch adults aged 65-80 years. We identified the contribution of nutrient dense foods, fortified foods and dietary supplements to the total intake of micronutrients. Nutrient density of foods was evaluated using the Nutrient Rich Food score 9.3. Nutrient intake inadequacies were observed for vitamin D, vitamin B6 and selenium. Conventional foods were the main source of vitamin D, vitamin B6 and selenium intake. Foods with the highest nutrient density contributed most to total vitamin B6 intake. In order to optimize nutrient intakes of elderly, combinations of natural food sources, fortified foods and dietary supplements should be considered. Chapter 3 provides a systematic review of the literature on human studies up to May 2014 that examined the role of dietary patterns in relation to cognitive decline or dementia. The results demonstrate that better adherence to a Mediterranean diet was associated with less cognitive decline, dementia or Alzheimer’s Disease (AD) in four out of six cross-sectional studies, six out of 12 longitudinal studies, one trial and three meta-analyses. Other healthy dietary patterns, among which the Healthy Diet Indicator, have shown to be associated with reduced cognitive decline and/or a reduced risk of dementia in all six cross-sectional studies and six out of eight longitudinal studies. The conclusion of this literature review was that more conclusive evidence is needed to come to more targeted and detailed dietary guidelines to prevent or postpone cognitive decline. In chapter 4 the association between the Healthy Diet Indicator (HDI) and cognitive functioning in older adults from three different cohort studies was investigated. The cohorts included in total 21,837 subjects from Europe (SENECA and the Rotterdam Study [RS]) and the Unites States (Nurses’ Health Study [NHS]). Cognitive functioning was measured using the Mini-Mental State Examination (MMSE) in SENECA and RS, and the Telephone Interview for Cognitive Status (TICS) in NHS. In all three cohorts, the HDI was not significantly associated with cognitive decline, nor with cognitive function. In chapter 5 the association of long-term adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with cognitive function and decline in older American women was examined. A total of 16,144 women from the Nurses’ Health Study, aged ≥70 years, who underwent cognitive testing a total of 4 times by telephone from 1995-2001 (baseline), with multiple dietary assessments between 1984 and the first cognitive exam were studied. Greater adherence to long-term DASH score was significantly associated with better average global cognition, verbal memory and TICS score at older ages, but not with cognitive decline. In chapter 6, the same cohort as in chapter 5 was studied to examine the association between long-term adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and decline. Higher MIND diet scores were associated with better verbal memory at older ages, but not with cognitive decline over 6 years in global cognition, verbal memory or TICS. Chapter 7 provides an overview of the NU-AGE (NUtrients and AGEing) dietary intervention study. The NU-AGE study is a randomized one-year intervention in 1,250 apparently healthy, independently living European subjects aged 65 to 80 years. Subjects were randomised into either the intervention group or the control group. Participants in the intervention group received dietary advice aimed at meeting the dietary recommendations of the ageing population. At the start of this thesis, the NU-AGE study was the first dietary intervention investigating the effect of a whole diet and providing targeted dietary recommendations for optimal health and quality of life in apparently healthy European elderly. In chapter 8, we evaluated if the NU-AGE intervention could be effective to shift the dietary intake of apparently healthy older adults aged 65-80 years living in Italy, the UK, the Netherlands, Poland, and France towards a more healthful diet. The NU-AGE index was created to assess adherence to the NU-AGE diet. At baseline and after one-year follow-up dietary intake was assessed by means of 7-day food records. In total, 1,296 participants were randomized and 1,145 participants completed the intervention (571 in intervention group, 570 in control group). After one-year follow-up, the intervention group improved mean intake of 13 out of 16 dietary recommendations of the NU-AGE diet (p

Objectives: To demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system.Methods: Twenty HNC patients were enrolled in this in-silico comparative planning study. Per patient, novice planners with less experience in dosimetry planning created an IMRT plan using an MCO system (RayStation). Furthermore, a conventionally planned clinical IMRT plan was available (Pinnacle(3)). All conventional IMRT and MCO-plans were blind-rated by two expert radiation-oncologists in HNC, using a 5-point scale (1-5 with 5 the highest score) assessment form comprising 10 questions. Additionally, plan quality was reported in terms of planning time, dosimetric and normal tissue complication probability (NTCP) comparisons. Inter-rater reliability was derived using the intra-class correlation coefficient (ICC).Results: In total, the radiation-oncologists rated 800 items on plan quality. The overall plan score indicated no differences between both planning techniques (conventional IMRT: 3.8 +/- 1.2 vs. MCO: 3.6 +/- 1.1, p = 0.29). The inter-rater reliability of all ratings was 0.65 (95% CI: 0.57-0.71), indicating substantial agreement between the radiation-oncologists. In 93% of cases, the scoring difference of the conventional IMRT and MCO-plans was one point or less. Furthermore, MCO-plans led to slightly higher dose uniformity in the therapeutic planning target volume, to a lower integral body dose (13.9 +/- 4.5 Gy vs. 12.9 +/- 4.0 Gy, p Conclusions: MCO planning enables novice treatment planners to create high quality IMRT plans for HNC patients. Plans were created with vastly reduced planning times, requiring less resources and a short learning curve.

Background: Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians. Objective: The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y. Design: Data on dietary intake, psychological test performance, and biochemical variables of cobalamin status were collected from 48 adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y, subsequently followed by lactovegetarian or omnivorous diets, and from 24 subjects (aged 10-18 y) who were fed omnivorous diets from birth onward. Thirty-one subjects from the previously macrobiotic group were cobalamin deficient according to their plasma methylmalonic acid concentrations. Seventeen previously macrobiotic subjects and all control subjects had normal cobalamin status. Results: The control subjects performed better on most psychological tests than did macrobiotic subjects with low or normal cobalamin status. A significant relation between test score and cobalamin deficiency (P = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: -0.48, -0.08). This effect became more pronounced (P = 0.003) within the subgroup of macrobiotic subjects (correlation coefficient: -0.38; 95% CI: -0.62, - 0.14). Conclusion: Our data suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adolescents.

Adverse drug effects are manifold and heterogenous. Many situations may hamper the signalling (i.e. the detection of early warning signs) of adverse effects and new signals often differ from previous experiences. Signals have qualitative and quantitative aspects. Different categories of adverse effects need different methods for detection. Current pharmacovigilance is predominantly based on spontaneous reporting and is mainly helpful in detecting type B effects (those effects that are often allergic or idiosyncratic reactions, characteristically occurring in only a minority of patients and usually unrelated to dosage and that are serious, unexpected and unpredictable) and unusual type A effects (those effects that are related to the pharmacological effects of the drug and are dosage-related). Examples of other sources of signals are prescription event monitoring, large automated data resources on morbidity and drug use (including record linkage), case-control surveillance and follow-up studies. Type C effects (those effects related to an increased frequency of 'spontaneous' disease) are difficult to study, however, and continue to pose a pharmacoepidemiological challenge. Seven basic considerations can be identified that determine the evidence contained in a signal: quantitative strength of the association, consistency of the data, exposure response relationship, biological plausibility, experimental findings, possible analogies and the nature and quality of the data. A proposal is made for a standard signal management procedure at pharmacovigilance centres, including the following steps: signal delineation, literature search, preliminary inventory of data, collection of additional information, consultation with the World Health Organization Centre for International Drug Monitoring and the relevant drug companies, aggregated data assessment and a report in writing. A better understanding of the conditions and mechanisms involved in the detection of adverse drug effects may further improve strategies for pharmacovigilance.

Monoclonal anti-nuclear antibodies which are complexed to nucleosomes are able to bind to the glomerular basement membrane (GBM) in vivo, whereas purified antibodies do not bind. The positively charged histone moieties in the nucleosome are-responsible for the binding to anionic determinants in the GBM. We tested the hypothesis that the specificity of the autoantibodies complexed to the nucleosome influences the glomerular binding of the antibody-nucleosome complex. We induced the formation of these immune complexes in vivo, by intraperitoneal inoculation of hybridomas producing monoclonal anti-nuclear antibodies (four anti-histone, three anti-double stranded (ds)DNA and three anti-nucleosome antibodies) into nude BALB/c mice. In ascites and plasma from the mice inoculated with these hybridomas, nucleosome/autoantibody complexes were detected in comparable amounts. Immunofluorescence of kidney sections revealed that about 60% of the mice inoculated with anti-nucleosome or anti-dsDNA hybridomas had immunoglobulin deposits in the GBM, whereas only 15% of the mice with anti-histone hybridomas showed these deposits (por = 0.04). In the Matrigel-ELISA (used as a GBM surrogate) ascites from anti-nucleosome or anti-DNA hybridomas displayed significantly higher titers (por = 0.002) than ascites from anti-histone hybridomas. In conclusion, nucleosome/immunoglobulin complexes comprising anti-nucleosome or anti-dsDNA auto-antibodies do bind more frequently to the GBM in vivo than nucleosome/immunoglobulin complexes containing anti-histone antibodies. It therefore appears that the specificity of the antibody bound to the nucleosome is a critical determinant for the nephritogenic potential of the nucleosome-autoantibody complex.

Summary: in this; study we examined the effects of long-term treatment of 19 patients with primary hypertension with the sr adrenoceptor antagonist atenolol on norepinephrine and epi­ nephrine kinetics, at rest and during sympathoadrenal stimula­ tion by lower body negative pressure. Norepinephrine and epinephrine kinetics were measured by using the radioisotopedi luti on technique by steady-state infusion of tritiated norepi­ nephrine and epinephrine. The patients were studied before and at the end of 3 months of treatment with atenolol (50 or 100 mg daily). A control group of four normotensive subjects was stud­ ied before and after 3 months without any drug treatment. In this group, only arterial blood samples were collected without infu­ sion of the tritiated catecholamines. Atenolol decreased blood pressure and heart rate, but forearm vascular resistance was not affected by atenolol. During atenolol, baseline arterial plasma epinephrine decreased from 0.23 ± O.02 to U.17 ± O.Oi nM (p < 0,05), and this was accompanied by a decrease in total body ep­ inephrine spillover from 0,50 ± 0.05 to 0.35 ± 0.04 nmol/min (p < 0.05), In the control group, arterial plasma epinephrine had not decreased after 3 months. In addition, the increment of arterial plasma epinephrine during lower body negative pressure at-40 mm Hg was attenuated during atenolol. Atenolol had no effect on total body and forearm norepinephrine spillover rates, either at rest or during lower body negative pressure. Clearance ivtes of epinephrine and norepinephrine were not significantly ef­ fected by atenolol. These results suggest that treatment of pa­ tients with primary hypertension with the s j-adrenoceptor blocker atenolol inhibits the adrenomedullary secretion of epi­ nephrine, but it does not affect the biochemical indices of sympathoneural activity, It remains speculative whether this selec­ tive effect of atenolol on epinephrine secretion contributes to its hypotensive action and to its cardioprotective effects in the long term. KeyWords: s (-Adrenergic— Sympathoadrenal activity— Hypertension— Catecholamines.

Heparin and heparinoids prevent the binding of immune complexes containing nucleosomal antigens to the GBM and delay nephritis in MRL/lpr mice. Monoclonal anti-nucleosome antibodies (mAbs) complexed to nucleosomal antigens can bind to DNA and to heparan sulfate (HS) in ELISA and to the GBM in vivo in a rat renal perfusion system, whereas non-complexed mAbs do not bind [1]. In this study, we analyzed whether heparin (HEP) or N-desulfated/acetylated heparins (DSA-HEP), structurally and functionally strongly related to HS, are able to prevent the binding of these complexed mAbs to DNA and to HS in vitro and to rat GBM in vivo. In ELISA the binding of nucleosome complexed anti-nucleosome antibodies to DNA and HS was inhibited dose-dependently by HEP, DSA-HEP and low molecular weight (LMW) DSA-HEP. Intravenous injection of nucleosome/anti-nucleosome immune complexes without heparin/heparinoids in BALB/c mice led to GBM binding, while simultaneous injection of heparin/heparinoids with complexed antibodies or pretreatment with heparin subcutaneously prior to injection of complexes prevented this binding. Subsequently, we tested the preventive effect of HEP, DSA-HEP and LMW-DSA-HEP on progression of renal disease in MRL/lpr mice. Treatment was started at an age of eight weeks in a dose of 50 µg daily. With all three drugs albuminuria was significantly delayed compared to PBS treated controls (cumulative incidence of proteinuria at 20 weeks in controls 60% vs. 13%, 14% and 6% respectively for HEP, DSA-HEP and LMW-DSA-HEP; P < 0.05). At week 21 the glomerulonephritis was histologically less severe in heparin/heparinoid treated animals (P = 0.02). In immunofluorescence the amount of immunoglobulin and C3 deposits in the glomerular capillary wall tended to be less in heparin/heparinoid treated mice compared to PBS treated controls (P = 0.07). Furthermore, at 20 weeks anti-HS levels in plasma of heparin/heparinoid treated mice were significantly lower (P < 0.05). We conclude that interaction of heparin or heparin analogs with HS reactive immune complexes containing nucleosomal antigens prevents the binding of these immune complexes to the GBM and delays nephritis in MRL/lpr mice.

Recently, anti-nucleosome antibodies, which do not bind to DNA or to individual histones, have been identified in longitudinal studies in lupus mice. These anti-nucleosome antibodies occur early in spontaneous SLE and are formed prior to other anti-nuclear specificities. However, nucleosomal epitopes are yet to be fully characterized. We selected a panel of six monoclonal anti-nucleosome antibodies (mAbs) (#2, #32, #34, PL2-6, LG8-1 and LG10-1) derived from lupus mice. These mAbs were tested in ELISA on subnucleosome structures and on a panel of 53 histone peptides, covering the entire sequence of the five histones. Two mAbs reacted with one of these peptides, but the reactivity hardly exceeded the background reactivity. Based on the nucleosome and subnucleosome ELISA we identified different recognition patterns. Three mAbs showed the highest reactivity towards the intact nucleosome. For two of them (#32 and LG8-1) the nucleosomal epitope was primarily located on H2A-H2B/DNA, whereas for mAb #34 this primary epitope was located on H3/H4/DNA. Two mAbs (#2 and PL2-6) showed the highest reactivity with H2A-H2B/DNA and one mAb (LG10-1) recognized H3-H4/DNA. In the subnucleosome ELISA all but one (mAb #32) recognized more than one epitope, including DNA complexed to a variety of cationic molecules. Comparing these reactivities we identified for all mAbs one specific nucleosomal epitope, whereas reactivity with other subnucleosomes was comparable to the reactivity towards DNA complexed with cationic molecules. In inhibition experiments both in ELISA and in immunofluorescence it was found that only one of the mAbs (i.e. PL2-6), recognizing an epitope on H2A-H2B/DNA as primary epitope, could be inhibited by H2A-H2B/DNA in fluid phase. The two mAbs recognizing an epitope on H3-H4/DNA as primary epitope could be inhibited by H3-H4/DNA in fluid phase. From these analyses, we conclude first that for these nucleosome specific mAbs linear histone peptides are not Fiery important. Second, that these mAbs all recognize different epitopes on both H2A/H2B-DNA and H3/H4-DNA and third that some solid phase H2A/H2B-DNA epitopes are not expressed on fluid phase H2A/H2B-DNA. Our findings suggest that in SLE the nucleosome can act as auto-antigen and that there is no immunodominant beta cell epitope within the nucleosome. (C) 1996 Academic Press Limited

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-regulated, cAMP-activated chloride channel located in the apical membrane of many epithelial secretory cells. Here we report cloning of a cAMP-activated epithelial basolateral chloride conductance regulator (EBCR) that appears to be a basolateral CFTR counterpart. This novel chloride channel or regulator shows 49% identity with multidrug resistance-associated protein (MRP) and 29% identity with CFTR. On expression in Xenopus oocytes, EBCR confers a cAMP-activated chloride conductance that is inhibited by the chloride channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamine)benzoic acid, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. Northern blot analysis reveals high expression in small intestine, kidney, and liver. In kidney, immunohistochemistry shows a conspicuous basolateral localization mainly in the thick ascending limb of Henle's loop, distal convoluted tubules and to a lesser extent connecting tubules. These data suggest that in the kidney EBCR is involved in hormone-regulated chloride reabsorption.

The link between modern lifestyles and increasing levels of chronic heart disease, obesity, stress and poor mental health is a concern across the world. The cost of dealing with these conditions places a large burden on national public health budgets so that policymakers are increasingly looking at prevention as a cost-effective alternative to medical treatment. Attention is turning towards interactions between the environment and lifestyles. Exploring the relationships between health, natural environments in general, and forests in particular, this groundbreaking book is the outcome of the European Union’s COST Action E39 ‘Forests, Trees and Human Health and Wellbeing’, and draws together work carried out over four years by scientists from 25 countries working in the fields of forestry, health, environment and social sciences. While the focus is primarily on health priorities defined within Europe, this volume explicitly draws also on research from North America and elsewhere and will have relevance worldwide. A state-of-the-art analysis of the global research on the topic of forests and human health, a key contribution of the book is its synthesis of material across both disciplines and nations, providing a vital reference for researchers in forestry, health, natural resource management and environmental policy. Currently the only unified body of work on this topic, the book will also be an important tool for those working in both health and environment policy and practice.

Associations between blood pressure and nutrition-related variables (body mass index, dietary intake, and 24-hr excretion of sodium, potassium, magnesium, and calcium in the urine) were investigated in men (n = 138) and women (n = 117) 65-79 years old not using drugs known to affect blood pressure and not on a diet. Among men, body mass index was positively and creatinine clearance was inversely associated with systolic blood pressure, whereas body mass index and urinary sodium:potassium ratio were positively associated with diastolic blood pressure. Among women, both age and urinary calcium:creatinine ratio were positively associated with systolic as well as diastolic blood pressure. Coffee consumption was positively correlated with blood pressure and urinary calcium:creatinine ratio among the women. From the results it appears that, besides ''normal'' weight, increased potassium intake and urinary excretion may exert a protective effect among elderly men against hypertension when sodium exposure is relatively high. The positive association between urinary calcium:creatinine ratio and blood pressure among the women may be partly due to coffee consumption. Chemicals/CAS: Calcium, 7440-70-2; Creatinine, 60-27-5; Magnesium, 7439-95-4; Potassium, 7440-09-7; Sodium, 7440-23-5

This paper gives a brief overview of the research literature on the effects of nature and green space on human health and well-being, with special attention to green areas in residential environments. A preliminary descriptive framework is presented and used to delineate the focus of the paper. The review of the studies is organized by the mechanisms that are supposed to explain the positive effect of nature on health. Seven of such mechanisms are distinguished. Although the evidence is mounting, the main conclusion is that the research on nature and human health is still in its early stages. The results thus far do not offer much support for evidence-based policy making nor can they be translated into practical guidelines yet.

AIMSTo compare the ultrasound (US) evolution and neurodevelopmental outcome of infants with localised (grade II) and extensive (grade III) cystic periventricular leucomalacia (c-PVL).METHODSOver a nine year period, c-PVL was diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were excluded from the study. Thirty nine infants with grade II PVL were compared with 39 infants with grade III PVL.RESULTSThe two populations were comparable for gestational age and birth weight. In infants with grade II PVL, cysts were noted to develop more often after the first month of life (53%) in contrast with grade III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to 12.63)). Cysts were also more often unilateral in grade II (54%) than in grade III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with grade II PVL, with ventriculomegaly being the only visible sequel in nine cases. In grade III PVL, cysts were still present in 25 of the 27 surviving infants. Nine infants with grade II PVL were free of motor sequelae at follow up compared with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two out of 29 children with grade II PVL who developed cerebral palsy achieved independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to 662)).CONCLUSIONSIn the cohort studied, 50% of the infants with c-PVL had a more localised form (grade II). In grade II PVL, the cysts developed beyond the first month of life in more than half of the cases and were often no longer visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential US should also be performed beyond the first month of life. Mild ventriculomegaly noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly less common and tended to be less severe in infants with grade II PVL than in those with grade III PVL.

The aim of this study was to investigate whether in stress-prone subjects, carbohydrate-rich, protein-poor food (CR/PP) diminished depressive mood and a cortisol response under controllable as well as uncontrollable laboratory stress. Twenty-two subjects with high stress proneness (HS) and 23 subjects with low stress proneness (LS) participated in a controllable- and uncontrollable-stress experiment during either a CR/PP or protein-rich, carbohydrate-poor (PR/CP) diet. Both controllable and uncontrollable laboratory stress significantly increased pulse rate and skin conductance in HS and LS subjects, whereas uncontrollable stress increased feelings of depression, anger, tension, and fatigue and decreased feelings of vigor. Only in HS subjects, a cortisol response and feelings of depression became lower under the CR/PP diet condition, irrespective of the controllability of the laboratory stressor, suggesting an increased ability to cope with stress. Because the CR/PP diet compared with the PR/CP diet previously has been found to cause a 42% increase in plasma tryptophan/ΣLNAA, seen as an indirect measure of increases in brain serotonin levels, the present results suggest that an enhanced serotonin function in HS subjects may be involved. (C) 2000 Elsevier Science Inc. Chemicals/CAS: Anti-Bacterial Agents; Nisin, 1414-45-5c

The TNO gastro-Intestinal tract Model (TIM) is a dynamic computer-controlled in vitro system that mimics the human physiological conditions in the stomach and small intestine. In the current TIM physiological parameters such as pH, temperature, peristaltic movements, secretion of digestion enzymes, bile and pancreatic juices, and absorption of digested products - by removal through dialysis - was simulated. Heterocyclic aromatic amines (HAA; viz. IQ, MeIQ, MeIQx and PhIP) were used as model compounds for food mutagens, and the passage through TIM was investigated for each of these compounds separately. Subsequently, the influence of a matrix and different rates of passage on the availability for absorption and distribution were studied in experiments with prepared meat, supplemented with MeIQx. Samples taken at various time points from the jejunal and ileal dialysates and from the lumen at the end of the small intestine (ileal delivery) were tested for the presence of mutagenic activity in the Ames test with Salmonella typhimurium strain TA98 as indicator, in the presence of mammalian metabolic activation (rat S9 mix). The results show that, comparable with the human in vivo situation, all four HAA are quickly removed (approx. 50% in 2 hr; approx. 95% in 6 hr) and mainly recovered from the lumen into the jejunal and ileal dialysates (94% of recovery). Only 5 ± 1.5% is recovered in the chyme at the end of the small intestine. When MeIQx was added to meat, its availability for absorption was slower, although the influence of the gastrointestinal passage time on the availability of MeIQx was more pronounced than this matrix effect. More MeIQx was found in the jejunal dialysate (23%; P < 0.01) and less in the ileal delivery (8%; P < 0.01) when simulating the gastrointestinal passage of solid meals was compared to simulating that of liquid meals. The present experiments demonstrate that TIM can be applied to study in vitro the availability of heterocyclic aromatic amines in the gastrointestinal tract. More generally, these studies indicate that TIM shows promise as a useful tool for various research purposes dealing with the availability for absorption of mutagenic as well as antimutagenic components in food. (C) 2000 Elsevier Science Ltd. Chemicals/CAS: Heterocyclic Compounds; Mutagens

Twenty-four men and 24 women, all nonsmoking, and maintaining normal dietary habits were assigned to 3 groups of 16. Each group comprising 4 males with "low" cholesterol levels (6 mmol/L) and 8 similarly matched females. A three-treatment, three-treatment period, cross-over design was adopted. The three treatments were placebo, 60 mg vitamin C/day (the recommended daily allowance) and 6 g vitamin C/day for 14 days with 6 weeks between treatments. Blood samples were taken at the end of each treatment period. Vitamin C supplementation significantly increased plasma vitamin C concentrations and total antioxidant capacity, but did not affect cholesterol status or plasma ras p21 protein levels. There was a nonsignificant dose-related decrease in plasma lipid peroxidation breakdown products. DNA damage, measured in lymphocytes by the Comet assay and chromosome aberration test, was not increased after vitamin C supplementation. Sensitivity to hydrogen peroxide (in the Comet assay) was also unaffected, but sensitivity to chromosome aberration induced by bleomycin was increased by supplementation. A significant gender difference was found in plasma vitamin C levels, antioxidant capacity, and number of chromosome aberrations. Results were independent of low and high cholesterol status.

The aim of this study was to investigate whether in stress-prone subjects, carbohydrate-rich, protein-poor food (CR/PP) diminished depressive mood and a cortisol response under controllable as well as uncontrollable laboratory stress. Twenty-two subjects with high stress proneness (HS) and 23 subjects with low stress proneness (LS) participated in a controllable- and uncontrollable-stress experiment during either a CR/PP or protein-rich, carbohydrate-poor (PR/CP) diet. Both controllable and uncontrollable laboratory stress significantly increased pulse rate and skin conductance in HS and LS subjects, whereas uncontrollable stress increased feelings of depression, anger, tension, and fatigue and decreased feelings of vigor. Only in HS subjects, a cortisol response and feelings of depression became lower under the CR/PP diet condition, irrespective of the controllability of the laboratory stressor, suggesting an increased ability to cope with stress. Because the CR/PP diet compared with the PR/CP diet previously has been found to cause a 42% increase in plasma tryptophan/ΣLNAA, seen as an indirect measure of increases in brain serotonin levels, the present results suggest that an enhanced serotonin function in HS subjects may be involved. (C) 2000 Elsevier Science Inc. Chemicals/CAS: Anti-Bacterial Agents; Nisin, 1414-45-5c

Objective: To investigate the impact of intensive group education on the Mediterranean diet on dietary intake and serum total cholesterol after 16 and 52 weeks, compared to a posted leaflet with the Dutch nutritional guidelines, in the context of primary prevention of cardiovascular disease (CVD). Design: Controlled comparison study of an intervention group given intensive group education about the Mediterranean diet and a control group of hypercholesterolaemic persons given usual care by general practitioners (GPs). Setting: A socioeconomically deprived area in the Netherlands with an elevated coronary heart disease (CHD) mortality ratio. Subjects: Two hundred and sixty-six hypercholesterolaemic persons with at least two other CVD risk factors. Results: After 52 weeks, the intervention group decreased total and saturated fat intake more than the control group (net differences were 1.8 en% (95%CI 0.2-3.4) and 1.1 en% (95%CI 0.4-1.9), respectively). According to the Mediterranean diet guidelines the intake of fish, fruit, poultry and bread increased in the intervention group, more than in the control group. Within the intervention group, intake of fish (+100%), poultry (+28%) and bread (+6%) was significantly increased after 1 year (P < 0.05). The intensive programme on dietary education did not significantly lower serum cholesterol level more (-3%) than the posted leaflet (-2%) (net difference 0.06 mmoll-1, 95%CI -0.10 to 0.22). Initially, the body mass index (BMI) decreased more in the intervention group, but after 1 year the intervention and control group gained weight equally (+1%). Conclusions: Despite beneficial changes in dietary habits in the intervention group compared with the control group, after 1 year BMI increased and total fat and saturated fat intake were still too high. Chemicals/CAS: Cholesterol, 57-88-5; Dietary Fats

The TNO gastro-Intestinal tract Model (TIM) is a dynamic computer-controlled in vitro system that mimics the human physiological conditions in the stomach and small intestine. In the current TIM physiological parameters such as pH, temperature, peristaltic movements, secretion of digestion enzymes, bile and pancreatic juices, and absorption of digested products - by removal through dialysis - was simulated. Heterocyclic aromatic amines (HAA; viz. IQ, MeIQ, MeIQx and PhIP) were used as model compounds for food mutagens, and the passage through TIM was investigated for each of these compounds separately. Subsequently, the influence of a matrix and different rates of passage on the availability for absorption and distribution were studied in experiments with prepared meat, supplemented with MeIQx. Samples taken at various time points from the jejunal and ileal dialysates and from the lumen at the end of the small intestine (ileal delivery) were tested for the presence of mutagenic activity in the Ames test with Salmonella typhimurium strain TA98 as indicator, in the presence of mammalian metabolic activation (rat S9 mix). The results show that, comparable with the human in vivo situation, all four HAA are quickly removed (approx. 50% in 2 hr; approx. 95% in 6 hr) and mainly recovered from the lumen into the jejunal and ileal dialysates (94% of recovery). Only 5 ± 1.5% is recovered in the chyme at the end of the small intestine. When MeIQx was added to meat, its availability for absorption was slower, although the influence of the gastrointestinal passage time on the availability of MeIQx was more pronounced than this matrix effect. More MeIQx was found in the jejunal dialysate (23%; P < 0.01) and less in the ileal delivery (8%; P < 0.01) when simulating the gastrointestinal passage of solid meals was compared to simulating that of liquid meals. The present experiments demonstrate that TIM can be applied to study in vitro the availability of heterocyclic aromatic amines in the gastrointestinal tract. More generally, these studies indicate that TIM shows promise as a useful tool for various research purposes dealing with the availability for absorption of mutagenic as well as antimutagenic components in food. (C) 2000 Elsevier Science Ltd. Chemicals/CAS: Heterocyclic Compounds; Mutagens

The main goal of prevention and health care for elderly people is optimizing 'quality of life'. Frail older persons have limited reserves and are therefore at an increased risk of a decline in health, which may lead to dependency and disability. This thesis focuses on the health-related effects of physical exercise and nutrient dense foods among non-institutionalized frail older people. First, criteria for identification of frailty were investigated using prospective cohort data. It was concluded that physical inactivity in combination with weight loss seems a practical and inexpensive screening criterion to identify functionally vulnerable persons among non-institutionalized elderly. Second, the results of a 17-weeks randomized controlled trial on a specific exercise and nutritional program in 217 frail, independently-living elderly (aged 67-96) are presented.The exercise program proved of benefit for functional status and immune response. Performance on 7 functional tests had significantly improved (+8%) in trained compared to non-trained subjects (-8%). The beneficial effect on the sum score of 7 fitness tests was also significant but smaller. Cellular immune response was measured by the delayed-type hypersensitivity skin test response against 7 recall antigens. The number of positive responses declined in non-exercising subjects (-26%) compared to an unchanged responsiveness among exercising subjects. Effects on self-rated disabilities, psychological well-being and self-rated health could not be demonstrated. Seventeen weeks of consumption of micronutrient enriched foods at physiological doses (25-100% of the RDA) did not affect functional status, cellular immune response or psychological well-being.In conclusion, exercise programs can be developed which are effective in preventing, slowing down or reversing the age-related decline in physical functioning and cellular immune response. Moreover, subjects highly appreciated the exercise program and the majority favored continuing program participation.

The main goal of prevention and health care for elderly people is optimizing 'quality of life'. Frail older persons have limited reserves and are therefore at an increased risk of a decline in health, which may lead to dependency and disability. This thesis focuses on the health-related effects of physical exercise and nutrient dense foods among non-institutionalized frail older people. First, criteria for identification of frailty were investigated using prospective cohort data. It was concluded that physical inactivity in combination with weight loss seems a practical and inexpensive screening criterion to identify functionally vulnerable persons among non-institutionalized elderly. Second, the results of a 17-weeks randomized controlled trial on a specific exercise and nutritional program in 217 frail, independently-living elderly (aged 67-96) are presented.The exercise program proved of benefit for functional status and immune response. Performance on 7 functional tests had significantly improved (+8%) in trained compared to non-trained subjects (-8%). The beneficial effect on the sum score of 7 fitness tests was also significant but smaller. Cellular immune response was measured by the delayed-type hypersensitivity skin test response against 7 recall antigens. The number of positive responses declined in non-exercising subjects (-26%) compared to an unchanged responsiveness among exercising subjects. Effects on self-rated disabilities, psychological well-being and self-rated health could not be demonstrated. Seventeen weeks of consumption of micronutrient enriched foods at physiological doses (25-100% of the RDA) did not affect functional status, cellular immune response or psychological well-being.In conclusion, exercise programs can be developed which are effective in preventing, slowing down or reversing the age-related decline in physical functioning and cellular immune response. Moreover, subjects highly appreciated the exercise program and the majority favored continuing program participation.ISBN:90-5808-125-7

Purpose: Several case reports have described familial aggregation of transitional cell carcinoma of the urinary tract but to our knowledge only 1 epidemiological study specifically addressed the issue of familial bladder cancer. We evaluated the extent of familial aggregation of transitional cell carcinoma among the population of Iceland.Materials and Methods: The first to third degree relatives of 190 patients with bladder, ureter or renal pelvis transitional cell carcinoma diagnosed between 1983 and 1992 in Iceland were identified through the Icelandic Cancer Family Resource. The records of these 12,328 relatives were subsequently linked to the 1965 to 1994 cancer registry. The observed occurrence of transitional cell carcinoma of the urinary tract was compared to the expected occurrence based on age, gender and calendar specific incidence rates. Observed-to-expected ratios and 95% confidence intervals were calculated.Results: In 41 of the 190 pedigrees at least 1 relative had transitional cell ...