The Effect of ACACB cis-Variants on Gene Expression and Metabolic Traits

Acetyl Coenzyme A carboxylase β (ACACB) is the rate-limiting enzyme in fatty acid oxidation, and continuous fatty acid oxidation in Acacb knock-out mice increases insulin sensitivity. Systematic human studies have not been performed to evaluate whether ACACB variants regulate gene expression and insulin sensitivity in skeletal muscle and adipose tissues. We sought to determine whether ACACB transcribed variants were associated with ACACB gene expression and insulin sensitivity in non-diabetic African American (AA) and European American (EA) adults.ACACB transcribed single nucleotide polymorphisms (SNPs) were genotyped in 105 EAs and 46 AAs whose body mass index (BMI), lipid profiles and ACACB gene expression in subcutaneous adipose and skeletal muscle had been measured. Allelic expression imbalance (AEI) was assessed in lymphoblast cell lines from heterozygous subjects in an additional EA sample (n = 95). Selected SNPs were further examined for association with insulin sensitivity in a cohort of 417 EAs and 153 AAs.ACACB transcribed SNP rs2075260 (A/G) was associated with adipose ACACB messenger RNA expression in EAs and AAs (p = 3.8×10(-5), dominant model in meta-analysis, Stouffer method), with the (A) allele representing lower gene expression in adipose and higher insulin sensitivity in EAs (p = 0.04). In EAs, adipose ACACB expression was negatively associated with age and sex-adjusted BMI (r = -0.35, p = 0.0002).Common variants within the ACACB locus appear to regulate adipose gene expression in humans. Body fat (represented by BMI) may further regulate adipose ACACB gene expression in the EA population

Research protocol of the NeedYD-study (Needs in Young onset Dementia): a prospective cohort study on the needs and course of early onset dementia

Contains fulltext : 89407.pdf (publisher's version ) (Open Access)BACKGROUND: Early onset dementia has serious consequences for patients and their family members. Although there has been growing attention for this patient group, health care services are still mainly targeted at the elderly. Specific knowledge of the needs of early onset dementia patients and their families is limited but necessary for the development of adequate health care services and specific guidelines. This research project is mainly targeted at delineating the course of early onset dementia, the functional characteristics and needs of early onset dementia patients and their caregivers, the risk factors for institutionalization and the interaction with the caring environment. METHODS/DESIGN: The NeedYD-study (Needs in Young Onset Dementia) is a longitudinal observational study investigating early onset dementia patients and their caregivers (n = 217). Assessments are performed every six months over two years and consist of interviews and questionnaires with patients and caregivers. The main outcomes are (1) the needs of patients and caregivers, as measured by the Camberwell Assessment of Needs for the Elderly (CANE) and (2) neuropsychiatric symptoms, as measured by the NeuroPsychiatric Inventory (NPI). Qualitative analyses will be performed in order to obtain more in-depth information on the experiences of EOD patients and their family members. The results of this study will be compared with comparable data on late onset dementia from a historical cohort. DISCUSSION: The study protocol of the NeedYD-study is presented here. To our knowledge, this study is the first prospective cohort study in this research area. Although some limitations exist, these do not outweigh the strong points of this study design

Coping and sickness absence

Objectives: The aim of this study is to examine the role of coping styles in sickness absence. In line with findings that contrast the reactive-passive focused strategies, problem-solving strategies are generally associated with positive results in terms of well-being and overall health outcomes; our hypothesis is that such strategies are positively related to a low frequency of sickness absence and with short lengths (total number of days absent) and durations (mean duration per spell). Methods: Using a prospective design, employees' (N = 3,628) responses on a self-report coping inventory are used to predict future registered sickness absence (i.e. frequency, length, duration, and median time before the onset of a new sick leave period). Results and conclusions: In accordance with our hypothesis, and after adjustment for potential confounders, employees with an active problem-solving coping strategy are less likely to drop out because of sickness absence in terms of frequency, length (longer than 14 days), and duration (more than 7 days) of sickness absence. This positive effect is observed in the case of seeking social support only for the duration of sickness absence and in the case of palliative reaction only for the length and frequency of absence. In contrast, an avoidant coping style, representing a reactive-passive strategy, increases the likelihood of frequent absences significantly, as well as the length and duration of sickness absence. Expression of emotions, representing another reactive-passive strategy, has no effect on future sickness absenteeism. The median time before the onset of a new episode of absenteeism is significantly extended for active problem-solving and reduced for avoidance and for a palliative response. The results of the present study support the notion that problem-solving coping and reactive-passive strategies are inextricably connected to frequency, duration, length and onset of sickness absence. Especially, active problem-solving decreases the chance of future sickness absence. © Springer-Verlag 2007

Dutch guideline on total hip prosthesis

Contains fulltext : 97840.pdf (publisher's version ) (Open Access

Collaborative stepped care for anxiety disorders in primary care: aims and design of a randomized controlled trial

Background. Panic disorder (PD) and generalized anxiety disorder (GAD) are two of the most disabling and costly anxiety disorders seen in primary care. However, treatment quality of these disorders in primary care generally falls beneath the standard of international guidelines. Collaborative stepped care is recommended for improving treatment of anxiety disorders, but cost-effectiveness of such an intervention has not yet been assessed in primary care. This article describes the aims and design of a study that is currently underway. The aim of this study is to evaluate effects and costs of a collaborative stepped care approach in the primary care setting for patients with PD and GAD compared with care as usual. Methods/design. The study is a two armed, cluster randomized controlled trial. Care managers and their primary care practices will be randomized to deliver either collaborative stepped care (CSC) or care as usual (CAU). In the CSC group a general practitioner, care manager and psychiatrist work together in a collaborative care framework. Stepped care is provided in three steps: 1) guided self-help, 2) cognitive behavioral therapy and 3) antidepressant medication. Primary care patients with a DSM-IV diagnosis of PD and/or GAD will be included. 134 completers are needed to attain sufficient power to show a clinically significant effect of 1/2 SD on the primary outcome measure, the Beck Anxiety Inventory (BAI). Data on anxiety symptoms, mental and physical health, quality of life, health resource use and productivity will be collected at baseline and after three, six, nine and twelve months. Discussion. It is hypothesized that the collaborative stepped care intervention will be more cost-effective than care as usual. The pragmatic design of this study will enable the researchers to evaluate what is possible in real clinical practice, rather than under ideal circumstances. Many requirements for a high quality trial are being met. Results of this study will contribute to treatment options for GAD and PD in the primary care setting. Results will become available in 2011. Trial registration. NTR1071

Chemical characterisation of archaeological glasses from the Hellenistic site of Jebel Khalid, Syria by electron probe microanalysis

© 2016 The Author(s). Background: Jebel Khalid is a single period Hellenistic site on the west bank of the Euphrates River in northern Syria. The occupation of the site dates from the early 3rd century BCE until its abandonment in the late 70s BCE. The so-called Governor's Palace, an administrative centre on the Acropolis of the site, overlooked this walled Greek garrison city. A considerable quantity of glass, predominantly drinking bowls, was excavated from this building complex. This study concerns the elemental analysis of glass samples from this assemblage by electron probe microanalysis (SEM-WDS). Results: The preliminary analyses presented in this report reveal that the Jebel Khalid glasses are of the silica-sodalime type fluxed with mineral soda, typical of late 1st millennium BCE glass composition. Manganese was employed as the chief decolourant. Glass compositions of monochrome bowls, core-formed and mosaic glass vessels are very similar, despite the different forms, colours and manufacturing techniques of the vessels. Conclusions: While the production centre for the Jebel Khalid glass remains elusive, the similarity to other published Hellenistic glasses from Greek mainland sites, Rhodes, Tel Anafa in Israel, and Gordion in central Turkey, indicates a tightly controlled composition with comparable batch ingredients. Without more comparative material of this date from the Near East and Greece, it is difficult to determine whether production of the vessel glass from this Seleucid site in the Near East occurred in the Aegean region or the Syro-Palestinian Levant, or both. Vessel style and archaeological context lean towards an Aegean connection, but until more comparative glass is analysed, and trace element and isotope data are considered, questions of primary and secondary production remain unresolved