Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia

OBJECTIVE: Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs. RESEARCH DESIGN AND METHODS: This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time. RESULTS: Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23–3.50) compared with current metformin use. CONCLUSIONS: Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin.Merck SA, Lyon, Franc

Microscopic calculations of Λ single-particle energies

A binding energy data for total baryon number A ≤ 208 and for Λ angular momenta ℓΛ ≤ 3 are analyzed in terms of phenomenological (but generally consistent with meson-exchange) ΛN and ΛNN potentials. The Fermi hypernetted chain technique is used to calculate the expectation values for the Λ binding to nuclear matter. Accurate effective ΛN and ΛNN potentials are obtained which are folded with the core-nucleus nucleon densities to calculate the Λ single-particle potential UΛ (r). We use a dispersive ANN potential but also include an explicit ρ dependence to allow for reduced repulsion in the surface, and the best fits have a large ρ dependence giving consistency with the variational Monte Carlo calculations for 5ΛHe. The exchange fraction of the ΛN space-exchange potential is found to be 0.2-0.3 corresponding to m*Λ ≃ (0.74 - 0.82)mΛ. Charge-symmetry breaking is found to be significant for heavy hypernuclei with a large neutron excess, with a strength consistent with that obtained from the A = 4 hypernuclei

Evolutionary history and identification of conservation units in the giant otter, Pteronura brasiliensis.

The giant otter, Pteronura brasiliensis, occupies a range including the major drainage basins of South America, yet the degree of structure that exists within and among populations inhabiting these drainages is unknown. We sequenced portions of the mitochondrial DNA (mtDNA) cytochrome b (612 bp) and control region (383 bp) genes in order to determine patterns of genetic variation within the species. We found high levels of mtDNA haplotype diversity (h = 0.93 overall) and support for subdivision into four distinct groups of populations, representing important centers of genetic diversity and useful units for prioritizing conservation within the giant otter. We tested these results against the predictions of three hypotheses of Amazonian diversification (Pleistocene Refugia, Paleogeography, and Hydrogeology). While the phylogeographic pattern conformed to the predictions of the Refugia Hypothesis, molecular dating using a relaxed clock revealed the phylogroups diverged from one another between 1.69 and 0.84 Ma, ruling out the influence of Late Pleistocene glacial refugia. However, the role of Plio-Pleistocene climate change could not be rejected. While the molecular dating also makes the influence of geological arches according to the Paleogeography Hypothesis extremely unlikely, the recent Pliocene formation of the Fitzcarrald Arch and its effect of subsequently altering drainage pattern could not be rejected. The data presented here support the interactions of both climatic and hydrological changes resulting from geological activity in the Plio-Pleistocene, in shaping the phylogeographic structure of the giant otter

Lambda-proton correlations in relativistic heavy ion collisions

The prospect of using lambda-proton correlations to extract source sizes in relativistic heavy ion collisions is investigated. It is found that the strong interaction induces a large peak in the correlation function that provides more sensitive source size measurements than two-proton correlations under some circumstances. The prospect of using lambda-proton correlations to measure the time lag between lambda and proton emissions is also studied.Comment: 4 pages, 3 figure, revtex style. Two short paragraphs are added at referees' recommendations. Phys. Rev. Lett. in pres

Relativistic Model of Detonation Transition from Neutron to Strange Matter

We study the conversion of neutron matter into strange matter as a detonation wave. The detonation is assumed to originate from a central region in a spherically symmetric background of neutrons with a varying radial density distribution. We present self-similar solutions for the propagation of detonation in static and collapsing backgrounds of neutron matter. The solutions are obtained in the framework of general relativistic hydrodynamics, and are relevant for the possible transition of neutron into strange stars. Conditions for the formation of either bare or crusted strange stars are discussed.Comment: 16 pages, 4 figures. Submitted to IJMP

SPARC-Dependent Cardiomyopathy in Drosophila

Background—The Drosophila heart is an important model for studying the genetics underpinning mammalian cardiac function. The system comprises contractile cardiomyocytes, adjacent to which are pairs of highly endocytic pericardial nephrocytes that modulate cardiac function by uncharacterized mechanisms. Identifying these mechanisms and the molecules involved is important because they may be relevant to human cardiac physiology. Methods and Results—This work aimed to identify circulating cardiomodulatory factors of potential relevance to humans using the Drosophila nephrocyte-cardiomyocyte system. A Kruppel-Like Factor 15 (dKlf15) loss-of-function strategy was used to ablate nephrocytes and then heart function and the hemolymph proteome were analysed. Ablation of nephrocytes led to a severe cardiomyopathy characterized by a lengthening of diastolic interval. Rendering adult nephrocytes dysfunctional by disrupting their endocytic function or temporally-conditional knock-down of dKlf15 led to a similar cardiomyopathy. Proteomics revealed that nephrocytes regulate the circulating levels of many secreted proteins, the most notable of which was the evolutionarily conserved matricellular protein SPARC (Secreted Protein Acidic and Rich in Cysteine), a protein involved in mammalian cardiac function. Finally, reducing SPARC gene dosage ameliorated the cardiomyopathy that developed in the absence of nephrocytes. Conclusions—The data implicate SPARC in the non-cell autonomous control of cardiac function in Drosophila and suggest that modulation of SPARC gene expression may ameliorate cardiac dysfunction in humans

Variational calculations of the Λ\Lambda-seperation energy of the Λ17_{\Lambda}^{17}O hypernucleus

Variational Monte Carlo calculations have been made for the $_{ \Lambda}^{17}$O hypernucleus using realistic two- and three-baryon interactions. A two pion exchange potential with spin- and space-exchange components is used for the $\Lambda$N potential. Three-body two-pion exchange and strongly repulsive dispersive $\Lambda$NN interactions are also included. The trial wave function is constructed from pair- and triplet-correlation operators acting on a single particle determinant. These operators consist of central, spin, isospin, tensor and three- baryon potential components. A cluster Monte Carlo method is developed for noncentral correlations and is used with up to four-baryon clusters in our calculations. The three-baryon $\Lambda$NN force is discussed.Comment: 24 pages, 2 figs available by fax., for publication in Phys. Rev.

The association between thyroid disorders and incident gout: population-based case-control study

Thyroid hormones influence kidney function and thereby might alter serum urate levels, a major risk factor for gouty arthritis.; To assess the risk of developing incident gout in association with hypothyroidism or hyperthyroidism.; Retrospective population-based case-control analysis.; UK-based Clinical Practice Research Datalink, a primary care research database.; We identified adult patients with a diagnosis of incident gout between 1990 and 2014. We matched one control to each gout case in terms of age, sex, general practice, calendar time, and years of active history in the database.; We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for developing gout in association with hypo- or hyperthyroidism and adjusted for potential confounders.; The study population encompassed 68,159 incident gout cases, of whom 78.8% were male, and the same number of matched controls. There was no increased risk of gout in patients with hypothyroidism: adjusted OR of gout of 1.12 (95% CI 1.05-1.20) compared with no hypothyroidism. Current short-term treatment of thyroid hormone replacement therapy was associated with an adjusted OR of gout of 1.54 (95% CI 1.24-1.92), compared with no treatment. Neither hyperthyroidism nor current treatment with thyroid suppression therapy was associated with gout (adjusted OR, 1.08 [95% CI 0.95-1.22] and 0.82 [95% CI 0.57-1.17], respectively).; This large observational study does not provide evidence that hypothyroidism or hyperthyroidism, irrespective of treatment, is associated with a clinically relevant increased risk of developing incident gout. There may be an exception among patients with newly diagnosed and treated hypothyroidism

Ecologia de populações de porco monteiro no Pantanal do Brasil

O porco monteiro chegou ao Pantanal há cerca de dois séculos e, desde então, tem sido considerado como a principal espécie cinegética (de interesse para a caça) na região. Suas populações vivem livres na planície e independentes da atividade humana, exceto pelo manejo tradicional que age como fator de controle populacional dos rebanhos. Considerando que a espécie apresenta potencial para utilização econômica e que pode vir a compor a pauta de produtos com certificação de origem no Pantanal, informações sobre a ecologia das populações presentes na planície são estratégicas. Este artigo apresenta um apanhado sobre as informações disponíveis a respeito da espécie e discute aspectos da dinâmica de suas populações, com base em projeções obtidas utilizando-se o software VORTEX 9.6.bitstream/CPAP-2010/57340/1/DOC106.pd