National Institute for Public Health and the Environment Bilthoven

Bilthoven, Netherlands

National Institute for Public Health and the Environment Bilthoven

Bilthoven, Netherlands
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Roswall N.,Danish Cancer Society | Angquist L.,Bispebjerg and Frederiksberg Hospitals The Capital Region | Ahluwalia T.S.,Novo Nordisk AS | Ahluwalia T.S.,Copenhagen University | And 19 more authors.
American Journal of Clinical Nutrition | Year: 2014

Background: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics.Objective: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI).Design: We conducted a case-cohort study with a median followup of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during followup. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models.Results: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/ y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI(β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations.Conclusions: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up. © 2014 American Society for Nutrition.


Yokel R.A.,University of Kentucky | Hussain S.,U.S. National Institutes of Health | Garantziotis S.,U.S. National Institutes of Health | Demokritou P.,Environmental Health | And 4 more authors.
Environmental Science: Nano | Year: 2014

This critical review evolved from a SNO Special Workshop on Nanoceria panel presentation addressing the toxicological risks of nanoceria: accumulation, target organs, and issues of clearance; how exposure dose/concentration, exposure route, and experimental preparation/model influence the different reported effects of nanoceria; and how can safer by design concepts be applied to nanoceria? It focuses on the most relevant routes of human nanoceria exposure and uptake, disposition, persistence, and resultant adverse effects. The pulmonary, oral, dermal, and topical ocular exposure routes are addressed as well as the intravenous route, as the latter provides a reference for the pharmacokinetic fate of nanoceria once introduced into blood. Nanoceria reaching the blood is primarily distributed to mononuclear phagocytic system organs. Available data suggest nanoceria's distribution is not greatly affected by dose, shape, or dosing schedule. Significant attention has been paid to the inhalation exposure route. Nanoceria distribution from the lung to the rest of the body is less than 1% of the deposited dose, and from the gastrointestinal tract even less. Intracellular nanoceria and organ burdens persist for at least months, suggesting very slow clearance rates. The acute toxicity of nanoceria is very low. However, large/accumulated doses produce granuloma in the lung and liver, and fibrosis in the lung. Toxicity, including genotoxicity, increases with exposure time; the effects disappear slowly, possibly due to nanoceria's biopersistence. Nanoceria may exert toxicity through oxidative stress. Adverse effects seen at sites distal to exposure may be due to nanoceria translocation or released biomolecules. An example is elevated oxidative stress indicators in the brain, in the absence of appreciable brain nanoceria. Nanoceria may change its nature in biological environments and cause changes in biological molecules. Increased toxicity has been related to greater surface Ce3+, which becomes more relevant as particle size decreases and the ratio of surface area to volume increases. Given its biopersistence and resulting increased toxicity with time, there is a risk that long-term exposure to low nanoceria levels may eventually lead to adverse health effects. This critical review provides recommendations for research to resolve some of the many unknowns of nanoceria's fate and adverse effects. © 2014 the Partner Organisations.


Lagoe R.J.,Hospital Executive Council Syracuse | Westert G.P.,National Institute for Public Health and the Environment Bilthoven
BMC Health Services Research | Year: 2010

Background: Hospital inpatient complications are one of a number of adverse health care outcomes. Reducing complications has been identified as an approach to improving care and saving resources as part of the health care reform efforts in the United States. An objective of this study was to describe the Potentially Preventable Complications software developed as a tool for evaluating hospital inpatient outcomes. Additional objectives included demonstration of the use of this software to evaluate the connection between health care outcomes and expenses in United States administrative data at the state and local levels and the use of the software to plan and implement interventions to reduce hospital complications in one U.S. metropolitan area. Methods: The study described the Potentially Preventable Complications software as a tool for evaluating these inpatient hospital outcomes. Through administrative hospital charge data from California and Maryland and through cost data from three hospitals in Syracuse, New York, expenses for patients with and without complications were compared. These comparisons were based on patients in the same All Patients Refined Diagnosis Related Groups and severity of illness categories. This analysis included tests of statistical significance. In addition, the study included a planning process for use of the Potentially Preventable Complications software in three Syracuse hospitals to plan and implement reductions in hospital inpatient complications. The use of the PPC software in cost comparisons and reduction of complications included tests of statistical significance. Results: The study demonstrated that Potentially Preventable Complications were associated with significantly increased cost in administrative data from the United States in California and Maryland and in actual cost data from the hospitals of Syracuse, New York. The implementation of interventions in the Syracuse hospitals was associated with the reduction of complications for urinary tract infection, decubitus ulcer, and pulmonary embolism. Conclusions: The study demonstrated that the Potentially Preventable Complications software could be used to evaluate hospital outcomes and related costs at the aggregate and diagnosis specific levels. It also indicated that the system could be used to plan and implement interventions to improve outcomes on an individual or multihospital basis. © 2010 Lagoe and Westert; licensee BioMed Central Ltd.


PubMed | University Utrecht, National Institute for Public Health and the EnvironmentBilthoven and National Institute for Public Health and the Environment Bilthoven
Type: | Journal: Frontiers in pharmacology | Year: 2016

Practical problems with the use of medicines, such as difficulties with breaking tablets, are an often overlooked cause for non-adherence. Tablets frequently break in uneven parts and loss of product can occur due to crumbling and powdering. Health characteristics, such as the presence of peripheral neuropathy, decreased grip strength and manual dexterity, can affect a patients ability to break tablets. As these impairments are associated with aging and age-related diseases, such as Parkinsons disease and arthritis, difficulties with breaking tablets could be more prevalent among older adults. The objective of this study was to investigate the relationship between age and the ability to break scored tablets.A comparative study design was chosen. Thirty-six older adults and 36 young adults were systematically observed with breaking scored tablets. Twelve different tablets were included. All participants were asked to break each tablet by three techniques: in between the fingers with the use of nails, in between the fingers without the use of nails and pushing the tablet downward with one finger on a solid surface. It was established whether a tablet was broken or not, and if broken, whether the tablet was broken accurately or not.The older adults experienced more difficulties to break tablets compared to the young adults. On average, the older persons broke 38.1% of the tablets, of which 71.0% was broken accurately. The young adults broke 78.2% of the tablets, of which 77.4% was broken accurately. Further analysis by mixed effects logistic regression revealed that age was associated with the ability to break tablets, but not with the accuracy of breaking.Breaking scored tablets by hand is less successful in an elderly population compared to a group of young adults. Health care providers should be aware that tablet breaking is not appropriate for all patients and for all drugs. In case tablet breaking is unavoidable, a patients ability to break tablets should be assessed by health care providers and instructions on the appropriate method of breaking should be provided.


PubMed | Wageningen University and National Institute for Public Health and the Environment Bilthoven
Type: | Journal: Frontiers in microbiology | Year: 2016

Campylobacter is well recognized as the leading cause of bacterial foodborne diarrheal disease worldwide, and is routinely found in meat originating from poultry, sheep, pigs, and cattle. Effective monitoring of Campylobacter contamination is dependent on the availability of reliable detection methods. The method of the International Organization for Standardization for the detection of Campylobacter spp. in food (ISO 10272-1:2006) recommends the use of Bolton broth (BB) as selective enrichment medium, including a pre-enrichment step of 4-6 h at 37C to revive sublethally damaged cells prior to incubation for 2 days at 41.5C. Recently the presence of abundantly growing extended spectrum -lactamase producing Enterobacteriaceae (ESBL bacteria) has become one of the most important factors that interfere with the isolation of Campylobacter, resulting in false-negative detection. However, detailed growth dynamics of Campylobacter and its competitors remain unclear, where these would provide a solid base for further improvement of the enrichment procedure for Campylobacter. Other enrichment broths, such as Preston broth (PB) and BB plus clavulanic acid (BBc) have been suggested to inhibit competitive flora. Therefore, these different broths were used as enrichments to measure the growth kinetics of several strains of Campylobacter jejuni and ESBL bacteria separately, in co-culture and of strains in chicken samples. The maximum cell numbers and often the growth rates of Campylobacter in mixed culture with ESBL bacteria were significantly lower than in single cultures, indicating severe suppression of Campylobacter by ESBL bacteria, also in naturally contaminated samples. PB and BBc successfully diminished ESBL bacteria and might therefore be a better choice as enrichment medium in possibly ESBL-bacteria contaminated samples. The efficacy of a pre-enrichment step in the BB ISO-procedure was not supported for cold-stressed and non-stressed cells. Therefore, omission of this step (4-6 h at 37C) might be advised to obtain a less troublesome protocol.


PubMed | National Institute for Public Health and the Environment Bilthoven
Type: | Journal: BMC health services research | Year: 2010

Hospital inpatient complications are one of a number of adverse health care outcomes. Reducing complications has been identified as an approach to improving care and saving resources as part of the health care reform efforts in the United States.An objective of this study was to describe the Potentially Preventable Complications software developed as a tool for evaluating hospital inpatient outcomes. Additional objectives included demonstration of the use of this software to evaluate the connection between health care outcomes and expenses in United States administrative data at the state and local levels and the use of the software to plan and implement interventions to reduce hospital complications in one U.S. metropolitan area.The study described the Potentially Preventable Complications software as a tool for evaluating these inpatient hospital outcomes. Through administrative hospital charge data from California and Maryland and through cost data from three hospitals in Syracuse, New York, expenses for patients with and without complications were compared. These comparisons were based on patients in the same All Patients Refined Diagnosis Related Groups and severity of illness categories. This analysis included tests of statistical significance.In addition, the study included a planning process for use of the Potentially Preventable Complications software in three Syracuse hospitals to plan and implement reductions in hospital inpatient complications. The use of the PPC software in cost comparisons and reduction of complications included tests of statistical significance.The study demonstrated that Potentially Preventable Complications were associated with significantly increased cost in administrative data from the United States in California and Maryland and in actual cost data from the hospitals of Syracuse, New York. The implementation of interventions in the Syracuse hospitals was associated with the reduction of complications for urinary tract infection, decubitus ulcer, and pulmonary embolism.The study demonstrated that the Potentially Preventable Complications software could be used to evaluate hospital outcomes and related costs at the aggregate and diagnosis specific levels. It also indicated that the system could be used to plan and implement interventions to improve outcomes on an individual or multihospital basis.


PubMed | National Institute for Public Health and the Environment Bilthoven, University of Veterinary Medicine Vienna, Humboldt University of Berlin, National University of La Plata and Radboud University Nijmegen
Type: | Journal: Frontiers in microbiology | Year: 2015

Pertussis is a highly contagious disease mainly caused by Bordetella pertussis. Despite the massive use of vaccines, since the 1950s the disease has become re-emergent in 2000 with a shift in incidence from infants to adolescents and adults. Clearly, the efficacy of current cellular or acellular vaccines, formulated from bacteria grown in stirred bioreactors is limited, presenting a challenge for future vaccine development. For gaining insights into the role of B. pertussis biofilm development for host colonization and persistence within the host, we examined the biofilm forming capacity of eight argentinean clinical isolates recovered from 2001 to 2007. All clinical isolates showed an enhanced potential for biofilm formation compared to the reference strain Tohama I. We further selected the clinical isolate B. pertussis 2723, exhibiting the highest biofilm biomass production, for quantitative proteomic profiling by means of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, which was accompanied by targeted transcriptional analysis. Results revealed an elevated expression of several virulence factors, including adhesins involved in biofilm development. In addition, we observed a higher expression of energy metabolism enzymes in the clinical isolate compared to the Tohama I strain. Furthermore, all clinical isolates carried a polymorphism in the bvgS gene. This mutation was associated to an increased sensitivity to modulation and a faster rate of adhesion to abiotic surfaces. Thus, the phenotypic biofilm characteristics shown by the clinical isolates might represent an important, hitherto underestimated, adaptive strategy for host colonization and long time persistence within the host.


PubMed | University of Amsterdam, National Institute for Public Health and the Environment Bilthoven and Netherlands Institute for Neuroscience
Type: | Journal: Frontiers in pharmacology | Year: 2015

Our current 24-h society requires an increasing number of employees to work nightshifts with millions of people worldwide working during the evening or night. Clear associations have been found between shiftwork and the risk to develop metabolic health problems, such as obesity. An increasing number of studies suggest that the underlying mechanism includes disruption of the rhythmically organized body physiology. Normally, daily 24-h rhythms in physiological processes are controlled by the central clock in the brain in close collaboration with peripheral clocks present throughout the body. Working schedules of shiftworkers greatly interfere with these normal daily rhythms by exposing the individual to contrasting inputs, i.e., at the one hand (dim)light exposure at night, nightly activity and eating and at the other hand daytime sleep and reduced light exposure. Several different animal models are being used to mimic shiftwork and study the mechanism responsible for the observed correlation between shiftwork and metabolic diseases. In this review we aim to provide an overview of the available animal studies with a focus on the four most relevant models that are being used to mimic human shiftwork: altered timing of (1) food intake, (2) activity, (3) sleep, or (4) light exposure. For all studies we scored whether and how relevant metabolic parameters, such as bodyweight, adiposity and plasma glucose were affected by the manipulation. In the discussion, we focus on differences between shiftwork models and animal species (i.e., rat and mouse). In addition, we comment on the complexity of shiftwork as an exposure and the subsequent difficulties when using animal models to investigate this condition. In view of the added value of animal models over human cohorts to study the effects and mechanisms of shiftwork, we conclude with recommendations to improve future research protocols to study the causality between shiftwork and metabolic health problems using animal models.

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