Somatostatin receptor 5 and cannabinoid receptor 1 activation inhibit secretion of glucose-dependent insulinotropic polypeptide from intestinal K cells in rodents.

AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) is an enteroendocrine hormone that promotes storage of glucose and fat. Its secretion from intestinal K cells is triggered by nutrient ingestion and is modulated by intracellular cAMP. In view of the proadipogenic actions of GIP, this study aimed to identify pathways in K cells that lower cAMP levels and GIP secretion. METHODS: Murine K cells purified by flow cytometry were analysed for expression of G(αi)-coupled receptors by transcriptomic microarrays. Somatostatin and cannabinoid receptor expression was confirmed by quantitative RT-PCR. Hormone secretion in vitro was measured in GLUTag and primary murine intestinal cultures. cAMP was monitored in GLUTag cells using the genetically encoded sensor Epac2-camps. In vivo tolerance tests were performed in cannulated rats. RESULTS: Purified murine K cells expressed high mRNA levels for somatostatin receptors (Sstrs) Sstr2, Sstr3 and Sstr5, and cannabinoid receptor type 1 (Cnr1, CB1). Somatostatin inhibited GIP and glucagon-like peptide-1 (GLP-1) secretion from primary small intestinal cultures, in part through SSTR5, and reduced cAMP generation in GLUTag cells. Although the CB1 agonist methanandamide (mAEA) inhibited GIP secretion, no significant effect was observed on GLP-1 secretion from primary cultures. In cannulated rats, treatment with mAEA prior to an oral glucose tolerance test suppressed plasma GIP but not GLP-1 levels, whereas the CB1 antagonist AM251 elevated basal GIP concentrations. CONCLUSIONS/INTERPRETATION: GIP release is inhibited by somatostatin and CB1 agonists. The differential effects of CB1 ligands on GIP and GLP-1 release may provide a new tool to dissociate secretion of these incretin hormones and lower GIP but not GLP-1 levels in vivo

The association between retinal vascular geometry changes and diabetic retinopathy and their role in prediction of progression: an exploratory study

Background: The study describes the relationship of retinal vascular geometry (RVG) to severity of diabetic retinopathy (DR), and its predictive role for subsequent development of proliferative diabetic retinopathy (PDR). Methods. The research project comprises of two stages. Firstly, a comparative study of diabetic patients with different grades of DR. (No DR: Minimal non-proliferative DR: Severe non-proliferative DR: PDR) (10:10: 12: 19). Analysed RVG features including vascular widths and branching angles were compared between patient cohorts. A preliminary statistical model for determination of the retinopathy grade of patients, using these features, is presented. Secondly, in a longitudinal predictive study, RVG features were analysed for diabetic patients with progressive DR over 7 years. RVG at baseline was examined to determine risk for subsequent PDR development. Results: In the comparative study, increased DR severity was associated with gradual vascular dilatation (p = 0.000), and widening of the bifurcating angle (p = 0.000) with increase in smaller-child-vessel branching angle (p = 0.027). Type 2 diabetes and increased diabetes duration were associated with increased vascular width (p = <0.05 In the predictive study, at baseline, reduced small-child vascular width (OR = 0.73 (95 CI 0.58-0.92)), was predictive of future progression to PDR. Conclusions: The study findings suggest that RVG alterations can act as novel markers indicative of progression of DR severity and establishment of PDR. RVG may also have a potential predictive role in determining the risk of future retinopathy progression. © 2014 Habib et al.; licensee BioMed Central Ltd

Breathing adapted radiotherapy: a 4D gating software for lung cancer

<p>Abstract</p> <p>Purpose</p> <p>Physiological respiratory motion of tumors growing in the lung can be corrected with respiratory gating when treated with radiotherapy (RT). The optimal respiratory phase for beam-on may be assessed with a respiratory phase optimizer (RPO), a 4D image processing software developed with this purpose.</p> <p>Methods and Materials</p> <p>Fourteen patients with lung cancer were included in the study. Every patient underwent a 4D-CT providing ten datasets of ten phases of the respiratory cycle (0-100% of the cycle). We defined two morphological parameters for comparison of 4D-CT images in different respiratory phases: tumor-volume to lung-volume ratio and tumor-to-spinal cord distance. The RPO automatized the calculations (200 per patient) of these parameters for each phase of the respiratory cycle allowing to determine the optimal interval for RT.</p> <p>Results</p> <p>Lower lobe lung tumors not attached to the diaphragm presented with the largest motion with breathing. Maximum inspiration was considered the optimal phase for treatment in 4 patients (28.6%). In 7 patients (50%), however, the RPO showed a most favorable volumetric and spatial configuration in phases other than maximum inspiration. In 2 cases (14.4%) the RPO showed no benefit from gating. This tool was not conclusive in only one case.</p> <p>Conclusions</p> <p>The RPO software presented in this study can help to determine the optimal respiratory phase for gated RT based on a few simple morphological parameters. Easy to apply in daily routine, it may be a useful tool for selecting patients who might benefit from breathing adapted RT.</p

[11C]acetate PET/CT Visualizes Skeletal Muscle Exercise Participation, Impaired Function, and Recovery after Hip Arthroplasty; First Results

Based on skeletal muscle acetate physiology we aimed studying muscle function after hip arthroplasty with [(11)C]acetate PET

A critique of the WHO TobReg's "Advisory Note" report entitled: "Waterpipe tobacco smoking: health effects, research needs and recommended actions by regulators"

BACKGROUND AND AIM: The World Health Organisation Study Group on Tobacco Product Regulation (TobReg) has issued in 2005 an "Advisory Note" entitled: "Waterpipe Tobacco Smoking: Health Effects, Research Needs and Recommended Actions by Regulators". "Waterpipe" smoking is now considered a global public health threat and the corresponding artefact is actually known in the world under three main terms: hookah, narghile and shisha. This important report, the first ever prepared by WHO on the subject, poses two major problems. On one hand, its bibliographical references dismiss world chief relevant studies. On the other, it contains a certain number of errors of many orders: biomedical, sociological, anthropological and historical. The purpose of the present study is to highlight, one by one, where these weaknesses and errors lie and show how this official report can be considerably improved. RESULTS: We realise that widely advertised early anthropological studies were not taken into consideration whereas they shed a substantial light on this peculiar form of smoking and help understanding its high complexity. As for concrete errors to be found in this report, they deal with the chemistry of smoke, health-related effects, smoking patterns, description and history of the artefact and its use, gender and underage use aspects, prevention and research needs in this field. CONCLUSION: The scientific credibility of an international expert report may be at stake if its recommendations do not rely on sound objective research findings and a comprehensive review of the existing literature. The critical comments in this study will certainly help improve the present WHO report

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV

Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of 2.76 TeV per nucleon pair was studied using data collected with the CMS detector at the LHC. Fragmentation functions are constructed using charged-particle tracks with transverse momenta pt > 4 GeV for dijet events with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events are compared to those in pp data as a function of collision centrality, as well as dijet-pt imbalance. Special emphasis is placed on the most central PbPb events including dijets with unbalanced momentum, indicative of energy loss of the hard scattered parent partons. The fragmentation patterns for both the leading and subleading jets in PbPb collisions agree with those seen in pp data at 2.76 TeV. The results provide evidence that, despite the large parton energy loss observed in PbPb collisions, the partition of the remaining momentum within the jet cone into high-pt particles is not strongly modified in comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic