HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (<it>HNF1A</it>) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis. <it>HNF1A </it>is a frequent cause of monogenic diabetes, albeit with early-onset. Some uncommon subgroups like late-onset autosomal dominant diabetes mellitus (LOADDM) may present peculiar inheritance patterns with a stronger familial component. This study aims to investigate the relationship of <it>HNF1A </it>SNPs with cardiovascular risk factors in this group, as well as to characterize them in contrast with classical T2DM (CT2DM).</p> <p>Methods</p> <p>eighteen LOADDM (age at onset > 40 y.o.; diabetes in 3 contiguous generations, uniparental lineage) along with 48 CT2DM patients and 42 normoglycemic controls (N group) have been evaluated for cardiovascular risk factors and SNPs of <it>HNF1A</it>.</p> <p>Results</p> <p>LOADDM showed significantly higher frequencies of SNPs A98V (22.2% vs 2.1%, p = 0.02) and S487N (72.2% vs 43.8%, p = 0.049) of <it>HNF1A </it>compared to CT2DM. I27L did not show significant difference (66.7% vs 45.8%), but associated with lower risk of hypertriglyceridemia (OR 0.16, 95% CI 0.04–0.65, p = 0.01). "Protective effect" was independent from other well-known predictive risk factors for hypertriglyceridemia, such as waist circumference (OR 1.09 per 1 cm increase, p = 0.01) and HDL (OR 0.01 per 1 mmol/l, p = 0.005), after logistic regression.</p> <p>Conclusion</p> <p>Late onset autosomal dominant diabetes mellitus is clinically indistinguishable from classical type 2 diabetes individuals. However, LOADDM group is enriched for common <it>HNF1A </it>polymorphisms A98V and S487N. I27L showed "protective effect" upon hypertriglyceridemia in this sample of individuals, suggesting a role for <it>HNF1A </it>on diabetic individuals' lipid profile. These data contribute to the understanding of the complex interactions between genes, hyperglycemia and cardiovascular risk factors development in type 2 diabetes mellitus.</p

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

An Anti-Glitch in a Magnetar

Magnetars are neutron stars showing dramatic X-ray and soft $\gamma$-ray outbursting behaviour that is thought to be powered by intense internal magnetic fields. Like conventional young neutron stars in the form of radio pulsars, magnetars exhibit "glitches" during which angular momentum is believed to be transferred between the solid outer crust and the superfluid component of the inner crust. Hitherto, the several hundred observed glitches in radio pulsars and magnetars have involved a sudden spin-up of the star, due presumably to the interior superfluid rotating faster than the crust. Here we report on X-ray timing observations of the magnetar 1E 2259+586 which we show exhibited a clear "anti-glitch" -- a sudden spin down. We show that this event, like some previous magnetar spin-up glitches, was accompanied by multiple X-ray radiative changes and a significant spin-down rate change. This event, if of origin internal to the star, is unpredicted in models of neutron star spin-down and is suggestive of differential rotation in the neutron star, further supporting the need for a rethinking of glitch theory for all neutron stars

Cancellations in Neutrinoless Double Beta Decay and the Neutrino Mass Matrix

In a degenerate scheme with mass m_0 a complete analysis of the allowed range of the effective electron neutrino Majorana mass is performed. Special attention is paid to effects of cancellations caused either by intrinsic CP parities of the eigenstates (CP invariance) or by complex mixing matrix elements (CP violation). We investigate all possibilities and give in each case constraints on the phases, the relative CP parities or the neutrino mass scale. A solar mixing angle \sin^2 2 \theta smaller than 0.7 jeopardizes the degenerate mass scheme. A key value of /m_0 is identified, which is independent on the solar solution and would rule out certain schemes. Also it would answer the question regarding the presence of CP violation. Even if a total neutrino mass scale and an effective mass is measured, the value of the phases or parities is not fixed, unless in some special cases. The resulting uncertainty in the other mass matrix elements is at least of the same order than the one stemming from nuclear matrix elements calculations.Comment: 20 pages, 10 figures. Title, abstract and parts of the text change

Higgs-pair Production and Decay in Simplest Little Higgs Model

In the framework of the simplest little Higgs model (SLHM), we study the production of a pair of neutral CP-even Higgs bosons at the LHC. First, we examine the production rate and find that it can be significantly larger than the SM prediction. Then we investigate the decays of the Higgs-pair and find that for a low Higgs mass their dominant decay mode is hh->\eta\eta\eta\eta (\eta is a CP-odd scalar) while hh->b\bar{b}\eta\eta and hh->\eta\eta WW may also have sizable ratios. Finally, we comparatively study the rates of pp-> hh -> b\bar{b}\tau^+ \tau^-, pp->hh->b\bar{b}\gamma\gamma, and pp->hh->WWWW in the SLHM and the littlest Higgs models (LHT). We find that for a light Higgs, compared with the SM predictions, all the three rates can be sizably enhanced in the LHT but severely suppressed in the SLHM; while for an intermediately heavy Higgs, both the LHT and SLHM can enhance sizably the SM predictions.Comment: Version in Nucl. Phys.

Service utilization in community health centers in China: a comparison analysis with local hospitals

BACKGROUND: Being an important part of China's Urban Health Care Reform System, Community Health Centers (CHCs) have been established throughout the entire country and are presently undergoing substantial reconstruction. However, the services being delivered by the CHCs are far from reaching their performance targets. In order to assess the role of the CHCs, we examined their performance in six cities located in regions of South-East China. The purpose of this investigation was to identify the utilization and the efficiency of community health resources that are able to provide basic medical and public health services. METHODS: The study was approved by Peking University Health Science Center Institutional Reviewing Board (NO: IRB00001052-T1). Data were collected from all the local health bureaux and processed using SPSS software. Methods of analysis mainly included: descriptive analysis, paired T-test and one-way ANOVA. RESULTS: The six main functions of the CHCs were not fully exploited and the surveys that were collected on their efficiency and utilization of resources indicate that they have a low level of performance and lack the trust of local communities. Furthermore, the CHCs seriously lack funding support and operate under difficult circumstances, and residents have less positive attitudes towards them. CONCLUSION: The community health service must be adjusted according to the requirements of urban medical and health reform, taking into account communities' health needs. More research is required on the living standards and health needs of residents living within the CHC's range, taking into consideration the users' needs in expanding the newly implemented service, and at the same time revising the old service system so as to make the development of CHCs realistic and capable of providing a better service to patients. Several suggestions are put forward for an attainable scheme for developing a community health service

Quark masses and mixings in the RS1 model with a condensing 4th generation

We study the hierarchy of quark masses and mixings in a model based on a 5-dimensional spacetime with constant curvature of Randall-Sundrum type with two branes, where the Electroweak Symmetry Breaking is caused dynamically by the condensation of a 4th generation of quarks, due to underlying physics from the 5D bulk and the first KK gluons. We first study the hierarchy of quark masses and mixings that can be obtained from purely adjusting the profile localizations, finding that realistic masses are not reproduced unless non trivial hierarchies of underlying 4-fermion interactions from the bulk are included. Then we study global U(1) symmetries that can be imposed in order to obtain non-symmetric modified Fritzsch-like textures in the mass matrices that reproduce reasonably well quark masses and CKM mixings.Comment: Minor changes. Version accepted for publication in JHE

Genetic relationships between Candida albicans strains isolated from dental plaque, trachea, and bronchoalveolar lavage fluid from mechanically ventilated intensive care unit patients

Candida albicans often resides in the oral cavity of healthy humans as a harmless commensal organism. This opportunistic fungus can cause significant disease in critically ill patients, such as those undergoing mechanical ventilation in the intensive care unit (ICU) having compromised local airway defense mechanisms. The goal of this study was to determine the intra- and inter-patient genetic relationship between strains of C. albicans recovered from dental plaque, tracheal secretions, and the lower airway by bronchoalveolar lavage of patients undergoing mechanical ventilation. Three pulsed-field gel electrophoresis (PFGE) typing methods were used to determine the genetic relatedness of the C. albicans strains, including electrophoretic karyotyping (EK) and restriction endonuclease analysis of the genome using SfiI (REAG-S) and BssHII (REAG-B). The C. albicans isolates from dental plaque and tracheo-bronchial sites from the same patient were genetically indistinguishable and retained over time, whereas strains from different patients usually separated into different genotypes. Among the three methods, REAG-B proved to be the most discriminatory method to differentiate isolates. The finding of genetically similar strains from the oral and tracheo-bronchial sites from the same patient supports the notion that the oral cavity may serve as an important source for C. albicans spread to the trachea and lung of mechanically ventilated patients

Selected Topics on Rare Kaon Processes - in the Standard Model and Supergravity -

Rare kaon processes appear to be particularly suitable to study the extensions of the standard model, especially if the possibility for eventual direct evidence becomes unlikely. In this review, we discuss processes that are important as a test of either the standard model or supergravity. Moreover, some of these are important even for both the standard model and for supergravity. Particular attention is paid to the reduction of uncertainties in the calculation, especially the ones coming from the confinement effects. Recent approaches, such as chiral perturbation theory, the large $N_c$-expansion, QCD sum rules and lattice QCD, are discussed. This is found to be the best strategy in view of the fact that supersymmetric effects are rather tiny.Comment: 52 pages (14 figures available upon request), LaTex, LMU-TP 7/89, RBI-TP 4/89, final version July 1992, to be published in Fortschritte der Physi

Obesity‐induced diabetes and lower urinary tract fibrosis promote urinary voiding dysfunction in a mouse model

BACKGROUND Progressive aging‐ and inflammation‐associated fibrosis effectively remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and lower urinary tract symptoms (LUTS). In the current study, we sought to test whether senescence‐accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet‐induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM). METHODS To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months, then subjected to glucose tolerance tests, assessed for plasma insulin levels, evaluated for urinary voiding function, and assessed for lower urinary tract fibrosis. RESULTS The results of these studies show that SAMP6 mice and AKR/J background strain mice develop diet‐induced obesity and T2DM concurrent with urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and urethral tissue fibrosis. CONCLUSIONS Taken together, these studies suggest that obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are inextricably and biologically linked. Prostate 73: 1123–1133, 2013. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98367/1/22662_ftp.pd