Sitagliptin is effective and safe as add-on to insulin in patients with absolute insulin deficiency: a case series

<p>Abstract</p> <p>Introduction</p> <p>It is generally believed that incretin-based therapies are effective in patients possessing certain levels of preserved β-cell function. So far, there are no reports that show the effectiveness of dipeptidyl peptidase-4 inhibitors in patients who absolutely lack the capacity for endogenous insulin secretion.</p> <p>Case presentation</p> <p>This report describes the efficacy of sitagliptin in three Japanese patients (a 91-year-old Japanese woman with type 1 diabetes, a 54-year-old Japanese man with type 2 diabetes and a 30-year-old Japanese man with features of both type 1 and type 2 diabetes) who had no detectable post-meal C-peptide levels. Although they were receiving intensive insulin therapy together with some oral hypoglycemic agents, their glycemic control remained poor. Sitagliptin was added to the ongoing therapeutic regimen to provide better glycemic control. Although these patients had mild hypoglycemia, effective reductions of hemoglobin A1c levels were observed without any adverse events in the liver and kidney during the following 24 weeks. Two of the patients were able to reduce their insulin doses, and one of the patients could discontinue one of the oral hypoglycemic agents. There was no weight gain or gastrointestinal complaints among the three patients. Post-meal C-peptide levels remained undetectable after sitagliptin treatment.</p> <p>Conclusion</p> <p>This report demonstrates that sitagliptin is effective and safe as an add-on therapy to insulin in reducing blood glucose levels in patients who absolutely lack the capacity for endogenous insulin secretion. The improvement seen in glycemic control could not be due to enhanced endogenous insulin secretion, since post-meal C-peptide levels remained undetectable after sitagliptin treatment, but it could be a result of other factors (for example, suppression of glucagon levels). However, the glucagon-suppressive effect of sitagliptin is known to be rather weak and short-lived. Given this background, a novel hypothesis that the glycemic effects of this drug may be caused by mechanisms that are independent of the glucagon-like peptide 1 axis (extra-pancreatic effect) will be discussed.</p

Flavourful Production at Hadron Colliders

We ask what new states may lie at or below the TeV scale, with sizable flavour-dependent couplings to light quarks, putting them within reach of hadron colliders via resonant production, or in association with Standard Model states. In particular, we focus on the compatibility of such states with stringent flavour-changing neutral current and electric-dipole moment constraints. We argue that the broadest and most theoretically plausible flavour structure of the new couplings is that they are hierarchical, as are Standard Model Yukawa couplings, although the hierarchical pattern may well be different. We point out that, without the need for any more elaborate or restrictive structure, new scalars with "diquark" couplings to standard quarks are particularly immune to existing constraints, and that such scalars may arise within a variety of theoretical paradigms. In particular, there can be substantial couplings to a pair of light quarks or to one light and one heavy quark. For example, the latter possibility may provide a flavour-safe interpretation of the asymmetry in top quark production observed at the Tevatron. We thereby motivate searches for diquark scalars at the Tevatron and LHC, and argue that their discovery represents one of our best chances for new insight into the Flavour Puzzle of the Standard Model.Comment: 18 pp., 8 figures, references adde

In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-Synuclein within E. coli cells

α-Synuclein is a small protein strongly implicated in the pathogenesis of Parkinson’s disease and related neurodegenerative disorders. We report here the use of in-cell NMR spectroscopy to observe directly the structure and dynamics of this protein within E. coli cells. To improve the accuracy in the measurement of backbone chemical shifts within crowded in-cell NMR spectra, we have developed a deconvolution method to reduce inhomogeneous line broadening within cellular samples. The resulting chemical shift values were then used to evaluate the distribution of secondary structure populations which, in the absence of stable tertiary contacts, are a most effective way to describe the conformational fluctuations of disordered proteins. The results indicate that, at least within the bacterial cytosol, α-synuclein populates a highly dynamic state that, despite the highly crowded environment, has the same characteristics as the disordered monomeric form observed in aqueous solution

Increasing trends of soil greenhouse gas fluxes in Japanese forests from 1980 to 2009

Forest soils are a source/sink of greenhouse gases, and have significant impacts on the budget of these terrestrial greenhouse gases. Here, we show climate-driven changes in soil GHG fluxes (CO2 emission, CH4 uptake, and N2O emission) in Japanese forests from 1980 to 2009, which were estimated using a regional soil GHG model that is data-oriented. Our study reveals that the soil GHG fluxes in Japanese forests have been increasing over the past 30 years at the rate of 0.31 Tg C yr−2 for CO2 (0.23 % yr−1, relative to the average from 1980 to 2009), 0.40 Gg C yr−2 for CH4 (0.44 % yr−1), and 0.0052 Gg N yr−2 for N2O (0.27 % yr−1). Our estimates also show large interannual variations in soil GHG fluxes. The increasing trends and large interannual variations in soil GHG fluxes seem to substantially affect Japan's Kyoto accounting and future GHG mitigation strategies

Fluids in cosmology

We review the role of fluids in cosmology by first introducing them in General Relativity and then by applying them to a FRW Universe's model. We describe how relativistic and non-relativistic components evolve in the background dynamics. We also introduce scalar fields to show that they are able to yield an inflationary dynamics at very early times (inflation) and late times (quintessence). Then, we proceed to study the thermodynamical properties of the fluids and, lastly, its perturbed kinematics. We make emphasis in the constrictions of parameters by recent cosmological probes.Comment: 34 pages, 4 figures, version accepted as invited review to the book "Computational and Experimental Fluid Mechanics with Applications to Physics, Engineering and the Environment". Version 2: typos corrected and references expande

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Risk Factors for Posttraumatic Stress Disorder Among Deployed US Male Marines

<p>Abstract</p> <p>Background</p> <p>Combat exposure has been reported as one of the strongest risk factors for postdeployment posttraumatic stress disorder (PTSD) among military service members. Determining the impact of specific deployment-related exposures on the risk of developing PTSD has not been fully explored. Our study objective was to explore the relationship between specific combat exposures and other life experiences with postdeployment PTSD.</p> <p>Methods</p> <p>This study consisted of male Marines who completed a Recruit Assessment Program (RAP) survey during recruit training at the Marine Corps Recruit Depot in San Diego, California as well as a follow-up survey several years after recruit training. Study participants included those Marines who deployed to the current operations in Iraq or Afghanistan between the baseline and follow-up surveys. Multivariable logistic regression was performed to determine which significant exposures and experiences were associated with postdeployment PTSD.</p> <p>Results</p> <p>Of the 706 study participants, 10.8% screened positive for postdeployment PTSD. Those who reported feeling in great danger of death (odds ratio [OR] = 4.63, 95% confidence interval [CI]: 2.46-8.73), were shot or seriously injured (OR = 3.51, 95% CI: 1.58-7.77), saw someone wounded or killed (OR = 2.47, 95% CI: 1.08-5.67), and baseline (before recruit training) prior violence exposures (OR = 2.99, 95% CI: 1.46-6.10) were at increased odds for reporting PTSD symptoms. Number of deployments, number of close friends or relatives reported at follow-up, and enlisted pay grade were also significantly associated with postdeployment PTSD.</p> <p>Conclusions</p> <p>Combat exposures, specifically the threat of death, serious injury, and witnessing injury or death are significant risk factors for screening positive for postdeployment PTSD among male Marines as well as violence exposures prior to entering the Marine Corps, which are independent of future combat exposures. A thorough history of lifetime violence exposures should be pursued when considering a clinical diagnosis of PTSD.</p

The effects of nail rigidity on fracture healing in rats with osteoporosis

Background and purpose Stress shielding from rigid internal fixation may lead to refracture after removal of the osteosynthesis material. We investigated the effect of a low-rigidity (Ti-24Nb-4Zr-7.9Sn) intramedullary nail regarding stress shielding and bone healing of osteoporotic fractures in the rat

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Barriers to the acceptance of electronic medical records by physicians from systematic review to taxonomy and interventions

<p>Abstract</p> <p>Background</p> <p>The main objective of this research is to identify, categorize, and analyze barriers perceived by physicians to the adoption of Electronic Medical Records (EMRs) in order to provide implementers with beneficial intervention options.</p> <p>Methods</p> <p>A systematic literature review, based on research papers from 1998 to 2009, concerning barriers to the acceptance of EMRs by physicians was conducted. Four databases, "Science", "EBSCO", "PubMed" and "The Cochrane Library", were used in the literature search. Studies were included in the analysis if they reported on physicians' perceived barriers to implementing and using electronic medical records. Electronic medical records are defined as computerized medical information systems that collect, store and display patient information.</p> <p>Results</p> <p>The study includes twenty-two articles that have considered barriers to EMR as perceived by physicians. Eight main categories of barriers, including a total of 31 sub-categories, were identified. These eight categories are: A) Financial, B) Technical, C) Time, D) Psychological, E) Social, F) Legal, G) Organizational, and H) Change Process. All these categories are interrelated with each other. In particular, Categories G (Organizational) and H (Change Process) seem to be mediating factors on other barriers. By adopting a change management perspective, we develop some barrier-related interventions that could overcome the identified barriers.</p> <p>Conclusions</p> <p>Despite the positive effects of EMR usage in medical practices, the adoption rate of such systems is still low and meets resistance from physicians. This systematic review reveals that physicians may face a range of barriers when they approach EMR implementation. We conclude that the process of EMR implementation should be treated as a change project, and led by implementers or change managers, in medical practices. The quality of change management plays an important role in the success of EMR implementation. The barriers and suggested interventions highlighted in this study are intended to act as a reference for implementers of Electronic Medical Records. A careful diagnosis of the specific situation is required before relevant interventions can be determined.</p