Effects of experimental Neisseria meningitis W135 infection on serotoninergic parameters in mice

This study investigated the effects of Neisseria menigitidis W135 infection via intraperitoneal route on plasma free tryptophan concentration, brain serotonin and 5-hydroxyindole acetic acid (5-HIAA) levels in albino mice fed normal and tryptophan-enriched diets. The kinetics of appearance of viable bacteria in the blood, brain and liver following infection were also investigated. The serotoninergic parameters were determined by colorimetric and HPLC methods while colony counts were measured by plate count technique. Compared to normal diet, the tryptophan-enriched diet resulted in significantly (

Rigidity of compact Riemannian spin Manifolds with Boundary

In this article, we prove new rigidity results for compact Riemannian spin manifolds with boundary whose scalar curvature is bounded from below by a non-positive constant. In particular, we obtain generalizations of a result of Hang-Wang \cite{hangwang1} based on a conjecture of Schroeder and Strake \cite{schroeder}.Comment: English version of "G\'eom\'etrie spinorielle extrins\`eque et rigidit\'es", Corollary 6 in Section 3 added, to appear in Letters Math. Phy

Deformations of the hemisphere that increase scalar curvature

Consider a compact Riemannian manifold M of dimension n whose boundary \partial M is totally geodesic and is isometric to the standard sphere S^{n-1}. A natural conjecture of Min-Oo asserts that if the scalar curvature of M is at least n(n-1), then M is isometric to the hemisphere S_+^n equipped with its standard metric. This conjecture is inspired by the positive mass theorem in general relativity, and has been verified in many special cases. In this paper, we construct counterexamples to Min-Oo's conjecture in dimension n \geq 3.Comment: Revised version, to appear in Invent. Mat

Hidden Orbital Order in URu2Si2URu_{2}Si_{2}

When matter is cooled from high temperatures, collective instabilities develop amongst its constituent particles that lead to new kinds of order. An anomaly in the specific heat is a classic signature of this phenomenon. Usually the associated order is easily identified, but sometimes its nature remains elusive. The heavy fermion metal $URu_2Si_2$ is one such example, where the order responsible for the sharp specific heat anomaly at $T_0=17 K$ has remained unidentified despite more than seventeen years of effort. In $URu_{2}Si_{2}$, the coexistence of large electron-electron repulsion and antiferromagnetic fluctuations in $URu_2Si_2$ leads to an almost incompressible heavy electron fluid, where anisotropically paired quasiparticle states are energetically favored. In this paper we use these insights to develop a detailed proposal for the hidden order in $URu_2Si_2$. We show that incommensurate orbital antiferromagnetism, associated with circulating currents between the uranium ions, can account for the local fields and entropy loss observed at the $17 K$ transition; furthermore we make detailed predictions for neutron scattering measurements

Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction

New Findings What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non‐diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes. Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal‐averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT‐PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara–Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal‐averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2 , KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after‐depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+–Ca2+ exchange current. These data suggest that diabetes leads to pro‐arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population

Ferromagnetism in Ga1-xMnxP: evidence for inter-Mn exchange mediated by localized holes within a detached impurity band

We demonstrate that in ferromagnetic Ga1-xMnxP exchange is mediated by holes localized in a Mn-derived band. For x<0.06, infrared absorption and photoconductivity spectra indicate the presence of a Mn impurity band which is not merged with the valence band. At temperatures above TC (<65 K) electrical transport is dominated by excitation across this energy gap while nearest neighbor hopping dominates below TC. Magnetization measurements reveal a moment of 3.5 Bohr magnetons per substitutional Mn, while the large anomalous Hall signal unambiguously demonstrates that the ferromagnetism is carrier-mediated.Comment: Equation 1 correcte

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

The frequency of osteogenic activities and the pattern of intermittence between periods of physical activity and sedentary behaviour affects bone mineral content: the cross-sectional NHANES study

BACKGROUND: Sedentary behaviours, defined as non exercising seated activities, have been shown to have deleterious effects on health. It has been hypothesised that too much sitting time can have a detrimental effect on bone health in youth. The aim of this study is to test this hypothesis by exploring the association between objectively measured volume and patterns of time spent in sedentary behaviours, time spent in specific screen-based sedentary pursuits and bone mineral content (BMC) accrual in youth. METHODS: NHANES 2005–2006 cycle data includes BMC of the femoral and spinal region via dual-energy X-ray absorptiometry (DEXA), assessment of physical activity and sedentary behaviour patterns through accelerometry, self reported time spent in screen based pursuits (watching TV and using a computer), and frequency of vigorous playtime and strengthening activities. Multiple regression analysis, stratified by gender was performed on N = 671 males and N = 677 females aged from 8 to 22 years. RESULTS: Time spent in screen-based sedentary behaviours is negatively associated with femoral BMC (males and females) and spinal BMC (females only) after correction for time spent in moderate and vigorous activity. Regression coefficients indicate that an additional hour per day of screen-based sitting corresponds to a difference of −0.77 g femoral BMC in females [95% CI: -1.31 to −0.22] and of −0.45 g femoral BMC in males [95% CI: -0.83 to −0.06]. This association is attenuated when self-reported engagement in regular (average 5 times per week) strengthening exercise (for males) and vigorous playing (for both males and females) is taken into account. Total sitting time and non screen-based sitting do not appear to have a negative association with BMC, whereas screen based sedentary time does. Patterns of intermittence between periods of sitting and moderate to vigorous activity appears to be positively associated with bone health when activity is clustered in time and inter-spaced with long continuous bouts of sitting. CONCLUSIONS: Some specific sedentary pursuits (screen-based) are negatively associated with bone health in youth. This association is specific to gender and anatomical area. This relationship between screen-based time and bone health is independent of the total amount of physical activity measured objectively, but not independent of self-reported frequency of strengthening and vigorous play activities. The data clearly suggests that the frequency, rather than the volume, of osteogenic activities is important in counteracting the effect of sedentary behaviour on bone health. The pattern of intermittence between sedentary periods and activity also plays a role in bone accrual, with clustered short bouts of activity interspaced with long periods of sedentary behaviours appearing to be more beneficial than activities more evenly spread in time

Reduced risk of Barrett’s esophagus in statin users: case–control study and meta-analysis

Background: Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett’s esophagus. Aim: The purpose of this study was to examine the association between statin use and the presence of Barrett’s esophagus in patients having their first gastroscopy. Methods: We have performed a case–control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett’s esophagus. Male Barrett’s cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case–control studies. Results: Regular statin use was associated with a significantly lower incidence of Barrett’s esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37–0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21–0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett’s was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett’s, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett’s esophagus [pooled adjusted OR 0.63 (95 % CI 0.51–0.77)]. Conclusions: Statin use is associated with a reduced incidence of a new diagnosis of Barrett’s esophagus