18F-Labelled exendin to image GLP-1 receptor-expressing tissues: from niche to blockbuster?

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Obesity and diabetes mellitus association in rural community of Katana, South Kivu, in Eastern Democratic Republic of Congo : Bukavu Observ Cohort study results

Background: Factual data exploring the relationship between obesity and diabetes mellitus prevalence from rural areas of sub-Saharan Africa remain scattered and are unreliable. To address this scarceness, this work reports population study data describing the relationship between the obesity and the diabetes mellitus in the general population of the rural area of Katana (South Kivu in the Democratic Republic of the Congo). Methods: A cohort of three thousand, nine hundred, and sixty-two (3962) adults (>15 years old) were followed between 2012 and 2015 (or 4105 person-years during the observation period), and data were collected using the locally adjusted World Health Organization's (WHO) STEPwise approach to Surveillance (STEPS) methodology. The hazard ratio for progression of obesity was calculated. The association between diabetes mellitus and obesity was analyzed with logistic regression. Results: The diabetes mellitus prevalence was 2.8 % versus 3.5 % for obese participants and 7.2 % for those with metabolic syndrome, respectively. Within the diabetes group, 26.9 % had above-normal waist circumference and only 9.8 % were obese. During the median follow-up period of 2 years, the incidence of obesity was 535/100,000 person-years. During the follow-up, the prevalence of abdominal obesity significantly increased by 23 % (p < 0.0001), whereas the increased prevalence of general obesity (7.8 %) was not significant (p = 0.53). Finally, diabetes mellitus was independently associated with age, waist circumference, and blood pressure but not body mass index. Conclusion: This study confirms an association between diabetes mellitus and abdominal obesity but not with general obesity. On the other hand, the rapid increase in abdominal obesity prevalence in this rural area population within the follow-up period calls for the urgent promoting of preventive lifestyle measures

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation

Oxygen-sensitive 3He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO2) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acqiured on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (−1.75 mbar/s versus −0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients

Development of Bacterial Biofilms on Artificial Corals in Comparison to Surface-Associated Microbes of Hard Corals

Numerous studies have demonstrated the differences in bacterial communities associated with corals versus those in their surrounding environment. However, these environmental samples often represent vastly different microbial micro-environments with few studies having looked at the settlement and growth of bacteria on surfaces similar to corals. As a result, it is difficult to determine which bacteria are associated specifically with coral tissue surfaces. In this study, early stages of passive settlement from the water column to artificial coral surfaces (formation of a biofilm) were assessed. Changes in bacterial diversity (16S rRNA gene), were studied on artificially created resin nubbins that were modelled from the skeleton of the reef building coral Acropora muricata. These models were dip-coated in sterile agar, mounted in situ on the reef and followed over time to monitor bacterial community succession. The bacterial community forming the biofilms remained significantly different (R = 0.864 p<0.05) from that of the water column and from the surface mucus layer (SML) of the coral at all times from 30 min to 96 h. The water column was dominated by members of the α-proteobacteria, the developed community on the biofilms dominated by γ-proteobacteria, whereas that within the SML was composed of a more diverse array of groups. Bacterial communities present within the SML do not appear to arise from passive settlement from the water column, but instead appear to have become established through a selection process. This selection process was shown to be dependent on some aspects of the physico-chemical structure of the settlement surface, since agar-coated slides showed distinct communities to coral-shaped surfaces. However, no significant differences were found between different surface coatings, including plain agar and agar enhanced with coral mucus exudates. Therefore future work should consider physico-chemical surface properties as factors governing change in microbial diversity

Proactive and integrated primary care for frail older people: design and methodological challenges of the Utrecht primary care PROactive frailty intervention trial (U-PROFIT)

<p>Abstract</p> <p>Background</p> <p>Currently, primary care for frail older people is reactive, time consuming and does not meet patients' needs. A transition is needed towards proactive and integrated care, so that daily functioning and a good quality of life can be preserved. To work towards these goals, two interventions were developed to enhance the care of frail older patients in general practice: a screening and monitoring intervention using routine healthcare data (U-PRIM) and a nurse-led multidisciplinary intervention program (U-CARE). The U-PROFIT trial was designed to evaluate the effectiveness of these interventions. The aim of this paper is to describe the U-PROFIT trial design and to discuss methodological issues and challenges.</p> <p>Methods/Design</p> <p>The effectiveness of U-PRIM and U-CARE is being tested in a three-armed, cluster randomized trial in 58 general practices in the Netherlands, with approximately 5000 elderly individuals expected to participate. The primary outcome is the effect on activities of daily living as measured with the Katz ADL index. Secondary outcomes are quality of life, mortality, nursing home admission, emergency department and out-of-hours General Practice (GP), surgery visits, and caregiver burden.</p> <p>Discussion</p> <p>In a large, pragmatic trial conducted in daily clinical practice with frail older patients, several challenges and methodological issues will occur. Recruitment and retention of patients and feasibility of the interventions are important issues. To enable broad generalizability of results, careful choices of the design and outcome measures are required. Taking this into account, the U-PROFIT trial aims to provide robust evidence for a structured and integrated approach to provide care for frail older people in primary care.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2288">NTR2288</a></p

A kinematic examination of dual-route processing for action imitation

The dual-route model of imitation suggests that meaningful and meaningless actions are processed through either an indirect or direct route, respectively. Evidence indicates that the direct route is more cognitively demanding, since it relies on mapping visuospatial properties of the observed action on to a performed one. These cognitive demands might negatively influence reaction time and accuracy for actions performed following a meaningless action under time constraints. However, how meaningful and meaningless action imitation processing is reflected in movement kinematics is not yet clear. We wanted to confirm whether meaningless action performance incurs a reaction time cost, whether the cost is reflected in kinematics, and, more generally, to examine kinematic markers of emblematic meaningful and meaningless action imitation. We examined participants’ reaction time and wrist movements when they imitated emblematic meaningful or matched meaningless gestures in either blocks of the same action type, or mixed blocks. Meaningless actions were associated with a greater correction period at the end of the movement, possibly reflecting a strategy designed to ensure accurate completion for less familiar actions under time constraints. Furthermore, in mixed blocks, trials following meaningless actions had a significantly increased reaction time, supporting previous claims that route selection for action imitation may be stimulus-driven. However, there was only convincing evidence for this effect with an interval of ~2948ms, but not ~3573ms or ~2553ms, between movements. Future work motion-tracking the entire hand to assess imitation accuracy, and more closely examining the influence of duration between movements, may help to explain these effects