Divergent effects of liraglutide, exendin-4, and sitagliptin on beta-cell mass and indicators of pancreatitis in a mouse model of hyperglycaemia

AIMS:Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP4) inhibitors improve glucose tolerance by still incompletely understood mechanisms. Each class of antihyperglycemic drugs has also been proposed to increase pancreatitis risk. Here, we compare systematically the effects of two widely-used GLP-1 analogues, liraglutide and exendin-4, and the DPP4 inhibitor, sitagliptin, in the mouse. METHODS:C57BL6 mice were maintained for 131 days on a normal diet (ND) or a diet comprising 60% fat (HFD) before measurements of fasting blood glucose and insulin, and intraperitoneal glucose tolerance. Beta- and alpha- cell volume, and Reg3b immunoreactivity, were measured by immunohistochemical analysis of pancreatic slices. RESULTS:Whereas liraglutide (200 µg/kg) and exendin-4 (10 µg/kg) treatment reduced body weight and/or improved glucose tolerance, sitagliptin (10 mg/kg) was without effect on either parameter. Liraglutide caused a sharp reduction in beta-cell mass in both ND and HFD mice, whereas exendin-4 exerted no effect. By contrast, sitagliptin unmasked an action of high fat diet to increase beta-cell mass. Reg3B positive area was augmented by all three agents in normal chow-fed mice, whilst sitagliptin and exendin-4, but not liraglutide, affected this parameter in HFD animals. Correspondingly sitagliptin, but not the GLP-1 analogues, increased circulating amylase levels in ND and HFD mice. CONCLUSIONS:Liraglutide improves glucose tolerance in the mouse whilst exerting relatively modest effects on pancreatitis risk. Conversely, exendin-4 and sitagliptin, at doses which exert, respectively, minor or no effects on metabolic parameters, lead to signs of pancreatitis

A novel multivariate STeady-state index during general ANesthesia (STAN)

The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.The first author was supported by a scholarship from the Portuguese Foundation for Science and Technology (FCT SFRH/BD/35879/2007). The authors would also like to acknowledge the support of UISPA—System Integration and Process Automation Unit—Part of the LAETA (Associated Laboratory of Energy, Transports and Aeronautics) a I&D Unit of the Foundation for Science and Technology (FCT), Portugal. FCT support under project PEst-OE/EME/LA0022/2013.info:eu-repo/semantics/publishedVersio

Enzymatic degradation of starch thermoplastic blends using samples of different thickness

The material studied was a thermoplastic blend of corn starch with a poly(ethylene-vinyl alcohol) copolymer, SEVA-C. The influence of both the material’s exposed surface and enzyme concentration on degradation kinetics was studied. As α-amylase is present in the blood plasma, experiments were performed, varying the material thickness and the α-amylase between 50 and 100 units/l, at 37°C, lasting up to 90 days. Four different batches using SEVA-C and starch samples of different thickness were performed. The positive correlation between degradation rate and the exposed material surface was confirmed, since thin films with larger exposed surfaces were degraded faster than thick square plates having the same total mass. The degradation extent depends on the total amount of amorphous starch present in the formulation rather than on the amount of enzyme used and the minimum thickness to ensure maximum degradation was estimated to be close to 0.25 mm

Heterogeneities in leishmania infantum infection : using skin parasite burdens to identify highly infectious dogs

Background: The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods: Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results: Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions: Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs

Effects of an exercise programme with people living with HIV: Research in a disadvantaged setting

This study aimed to analyse the physical health effects of a community based 10-week physical activity programme with people living with HIV. It was developed, implemented and evaluated in a disadvantaged community in South Africa. A pre-post research design was chosen. Major recruitment and adherence challenges resulted in a small sample. Among the 23 participants who took part in both baseline and final testing, compliant participants (n = 12) were compared to non-compliant participants (n = 11). Immunological (CD4, viral load), anthropometric (height, weight, skinfolds and waist to hip ratio), muscular strength (h1RM) and cardiopulmonary fitness (time on treadmill) parameters were measured. The compliant and non-compliant groups were not different at baseline. Muscular strength was the parameter most influenced by compliance with the physical activity programme (F = 4.516, p = 0.047). Weight loss and improvement in cardiopulmonary fitness were restricted by the duration of the programme, compliance and influencing factors (e.g. nutrition, medication). The increase in strength is significant and meaningful in the context, as the participants goals were to look healthy and strong to avoid HIV related stigma. The improvements in appearance were a motivational factor, especially since the changes were made visible in a short time. Practical implications for health promotion are described. More research contextualised in disadvantaged settings is needed.DHE

Supercritical phase inversion of starch-poly(e-caprolactone) for tissue engineering applications

In this work, a starch-based polymer, namely a blend of starch-poly(ε-caprolactone) was processed by supercritical assisted phase inversion process. This processing technique has been proposed for the development of 3D structures with potential applications in tissue engineering applications, as scaffolds. The use of carbon dioxide as non-solvent in the phase inversion process leads to the formation of a porous and interconnected structure, dry and free of any residual solvent. Different processing conditions such as pressure (from 80 up to 150 bar) and temperature (45 and 55°C) were studied and the effect on the morphological features of the scaffolds was evaluated by scanning electron microscopy and micro-computed tomography. The mechanical properties of the SPCL scaffolds prepared were also studied. Additionally, in this work, the in vitro biological performance of the scaffolds was studied. Cell adhesion and morphology, viability and proliferation was assessed and the results suggest that the materials prepared are allow cell attachment and promote cell proliferation having thus potential to be used in some for biomedical applications.Ana Rita C. Duarte is grateful for financial support from Fundacao para a Ciencia e Tecnologia through the grant SFRH/BPD/34994/2007

Hydrodynamic Effects on Biofilm Development and Recombinant Protein Expression

Hydrodynamics play an important role in the rate of cell attachment and nutrient and oxygen transfer, which can affect biofilm development and the level of recombinant protein production. In the present study, the effects of different flow conditions on the development of Escherichia coli biofilms and the expression of a model recombinant protein (enhanced green fluorescent protein, eGFP) were examined. Planktonic and biofilm cells were grown at two different flow rates in a recirculating flow cell system for 7 days: 255 and 128 L h(-1) (corresponding to a Reynolds number of 4600 and 2300, respectively). The fluorometric analysis showed that the specific eGFP production was higher in biofilms than in planktonic cells under both hydrodynamic conditions (3-fold higher for 255 L h(-1) and 2-fold higher for 128 L h(-1)). In the biofilm cells, the percentage of eGFP-expressing cells was on average 52% higher at a flow rate of 255 L h(-1). Furthermore, a higher plasmid copy number (PCN) was obtained for the highest flow rate for both planktonic (244 PCN/cell versus 118 PCN/cell) and biofilm cells (43 PCN/cell versus 29 PCN/cell). The results suggested that higher flow velocities promoted eGFP expression in E. coli biofilms

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente