Detectie en preventie van kwetsbaarheid: Op zoek naar risicoprofielen voor fysieke,psychische, sociale en omgevingskwetsbaarheid

In order to provide proactive care and support for older people attention is needed for the prevention of frailty among older adults. Subsequently, accurate case finding of those who are more at risk of becoming frail is crucial to undertake specific preventive actions. This study investigates frailty and risk profiles of frailty among older people in order to support proactive detection. Hereby, frailty is conceived not only as a physical problem, but also refers to emotional, social, and environmental hazards. Using data generated from the Belgian Ageing Studies (N = 21,664 home-dwelling older people), a multinomial logistic regression model was tested which included socio-demographic and socio-economic indicators as well as the four dimensions of frailty (physical, social, psychological and environmental). Findings indicate that for both men and women having moved in the previous 10 years and having a lower household income are risk factors of becoming multidimensional frail. However, studying the different frailty domains, several risk profiles arise (e.?g. marital status is important for psychological frailty), and gender-specific risk groups are detected (e.?g. non-married men). This paper elaborates on practical implications and formulates a number of future research recommendations to tackle frailty in an ageing society.     

Assay of cholesterol 7 alpha-hydroxylase activity in rat hepatocytes in primary monolayer culture

A sensitive and precise method is described to assay cholesterol 7 alpha-hydroxylase activity in homogenates of rat hepatocytes cultured in monolayers for up to 76 h. The assay is based on measurement of the amount of radioactive cholesterol converted into 7 alpha-[14C]-hydroxycholesterol. Since no subcellular fractionation was applied to measure enzyme activity, this method is rapid and can be performed with cell protein, corresponding to as little as 1 to 2 million hepatocytes. Optimal assay conditions were determined and the reproducibility of this cholesterol 7 alpha-hydroxylase determination was established. Exogenous cholesterol (105 microM), solubilized in Tween 80, was added to saturate the enzyme, giving an apparent Km of 56 microM. Under these conditions, 70% of the cholesterol present in the homogenates is directly accessible to the cholesterol 7 alpha-hydroxylase. The detection limit of the assay was found to be about 10 pmol per incubation. A time course of the cholesterol 7 alpha-hydroxylase activity in cultured hepatocytes revealed that after an initial loss of approximately 60% of the activity as compared with 287 pmol/h/mg for freshly isolated cells, the enzyme activity was increased to the initial level in hepatocytes cultured for 52 h. This result and the finding that the cholesterol 7 alpha-hydroxylase activity was diminished by 94% after a 24-h incubation with 5 microM cycloheximide suggest that the enzyme activity is associated with de novo protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ML-236B (compactin) on biliary excretion of bile salts and lipids, and on bile flow, in the rat

To assess the importance of de novo cholesterol synthesis for bile salt formation, the effects of ML-236B (an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase) on biliary excretion of bile salts and lipids were studied in rats with permanent catheters in bile duct, heart and duodenum. In rats having their bile diverted continuously for 8 days, duodenal administration of ML-236B (50 mg/kg) caused an immediate transient choleresis, which subsided after 2 h. Concomitant with the choleresis concentrations of bile salt, phospholipid and cholesterol fell, but this decrease was maintained for 6 h. Consequently, ML-236B inhibited biliary output salts and lipids from the second till the sixth hour after injection. The kinetics of biliary excretion of intravenously injected [14C]taurocholate were not affected by ML-236B administration. In rats having their biliary catheter connected to the duodenal catheter, or in rats with prolonged bile diversion but treated with mevalonolactone, ML-236B again caused a transient choleresis (having subsided after 2 h), but now did not affect biliary excretion of bile salts and lipids. It is concluded that (1) ML-236B causes a transient bile salt-independent choleresis, (2) ML-236B depresses excretion of bile salts and lipids by blocking mevalonate synthesis and not by blocking the bile salt or lipid transport, (3) biliary excretions of phospholipids and cholesterol partly depend on excretion of bile salt, and (4) in rats with a prolonged total bile diversion newly formed mevalonate is a major substrate for bile salt synthesis.     

A Constitutive Model for a Maturing Fibrin Network

Blood clot formation is crucial to maintain normal physiological conditions but at the same time involved in many diseases. The mechanical properties of the blood clot are important for its functioning but complicated due to the many processes involved. The main structural component of the blood clot is fibrin, a fibrous network that forms within the blood clot, thereby increasing its mechanical rigidity. A constitutive model for the maturing fibrin network is developed that captures the evolving mechanical properties. The model describes the fibrin network as a network of fibers that become thicker in time. Model parameters are related to the structural properties of the network, being the fiber length, bending stiffness, and mass-length ratio. Results are compared with rheometry experiments in which the network maturation is followed in time for various loading frequencies and fibrinogen concentrations. Three parameters are used to capture the mechanical behavior including the mass-length ratio. This parameter agrees with values determined using turbidimetry experiments and is subsequently used to derive the number of protofibrils and fiber radius. The strength of the model is that it describes the mechanical properties of the maturing fibrin network based on it structural quantities. At the same time the model is relatively simple, which makes it suitable for advanced numerical simulations of blood clot formation during flow in blood vessels.     

Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: A systematic review

Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV). HPV-positive OPSCC is considered a distinct molecular entity with a better prognosis than HPV-negative cases of OPSCC. However, the exact pathogenic mechanisms underlying the differences in clinical and molecular behavior between HPV-positive and HPV-negative OPSCC remain poorly understood. Epigenetic events play an important role in the development of cancer. Hypermethylation of DNA in promoter regions and global hypomethylation are 2 epigenetic changes that have been frequently observed in human cancers. It is suggested that heterogeneous epigenetic changes play a role in the clinical and biological differences between HPV-positive and HPV-negative tumors. Unraveling the differences in methylation profiles of HPV-associated OPSCC may provide for promising clinical applications and may pave the road for personalized cancer treatment. This systematic review aims to assess the current state of knowledge regarding differences in promoter hypermethylation and global methylation between HPV-positive and HPV-negative OPSCC.     

Limited costs of wrong root placement in Rumex palustris in heterogeneous soils

Nutrient hot spots in the soil have a limited life span, but the costs and benefits for root foraging are still underexposed. We assessed short-term costs that may arise when a nutrient-rich patch induces root proliferation, but then rapidly disappears. Rumex palustris plants were grown with a homogeneous or a heterogeneous nutrient application. After root proliferation in a nutrient-rich patch, nutrient supply was switched from homogeneous to heterogeneous, and vice versa, or the patch location was changed. R. palustris proliferated its roots in the rich patch. After switching, the relative growth rates of the roots were adjusted to the novel pattern of nutrient availability. However, the changes in local root biomass lagged behind the rapid shift in nutrient supply, because the root mass realized in specific sectors could not be rapidly relocated. Despite this, R. palustris did not exhibit costs of switching in terms of biomass or nitrogen uptake. Our data suggest that rapid shifts in uptake rate and redistribution of nitrogen within the plant may have lowered the costs of incorrect root placement.     

Beyond MHC: signals of elevated selection pressure on Atlantic salmon (Salmo salar) immune‐relevant loci

Using Atlantic salmon (Salmo salar) as a model system, we investigated whether 18 microsatellites tightly linked to immune‐relevant genes have experienced different selection pressures than 76 loci with no obvious association with immune function. Immune‐relevant loci were identified as outliers by two outlier tests significantly more often than nonimmune linked loci (22% vs. 1.6%). In addition, the allele frequencies of immune relevant markers were more often correlated with latitude and temperature. Combined, these results support the hypothesis that immune‐relevant loci more frequently exhibit footprints of selection than other loci. They also indicate that the correlation between immune‐relevant loci and latitude may be due to temperature‐induced differences in pathogen‐driven selection or some other environmental factor correlated with latitude.     

Prevalence of SCN1A-Related Dravet Syndrome among Children Reported with Seizures following Vaccination: A Population-Based Ten-Year Cohort Study

Objectives

To determine the prevalence of Dravet syndrome, an epileptic encephalopathy caused by SCN1A-mutations, often with seizure onset after vaccination, among infants reported with seizures following vaccination. To determine differences in characteristics of reported seizures after vaccination in children with and without SCN1A-related Dravet syndrome.

Methods

Data were reviewed of 1,269 children with seizures following immunization in the first two years of life, reported to the safety surveillance system of the Dutch national immunization program between 1 January 1997 and 31 December 2006. Selective, prospective follow-up was performed of children with clinical characteristics compatible with a diagnosis of Dravet syndrome.

Results

In 21.9% (n = 279) of children, a diagnosis of Dravet syndrome could not be excluded based on available clinical data (median age at follow-up 16 months). Additional follow-up data were obtained in 83.9% (n = 234) of these children (median age 8.5 years).15 (1.2% of 1,269; 95%CI:0.6 to 1.8%) children were diagnosed with SCN1A-related Dravet syndrome. Of all reported seizures following vaccinations in the first year of life, 2.5% (95%CI:1.3 to 3.6%) were due to SCN1A-related Dravet syndrome, as were 5.9% of reported seizures (95%CI:3.1 to 8.7%) after 2^nd or 3^rd DTP-IPV-Hib vaccination.Seizures in children with SCN1A-related Dravet syndrome occurred more often with a body temperature below 38.5°C (57.9% vs. 32.6%, p = 0.020) and reoccurred more often after following vaccinations (26.7% vs. 4.0%, p = 0.003), than in children without a diagnosis of SCN1A-related Dravet Syndrome.

Conclusions

Although Dravet syndrome is a rare genetic epilepsy syndrome, 2.5% of reported seizures following vaccinations in the first year of life in our cohort occurred in children with this disorder. Knowledge on the specific characteristics of vaccination-related seizures in this syndrome might promote early diagnosis and indirectly, public faith in vaccination safety.     

The Development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): A Large-Scale Data Sharing Initiative

Introduction

In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons’ health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu).

Materials and Methods

A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden).

Results

Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies.

Discussion

TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations), standardised dataset pooled from various study protocols with different sampling frameworks. This unique implementation strategy improves efficiency and facilitates individual-level data meta-analysis.