Cerebrospinal Fluid Sex Steroid Hormones in Bacterial Meningitis

Unfavorable outcome in bacterial meningitis is related to excessive inflammation and higher inflammatory markers have been reported in female than in male patients. Sex steroid hormones have immunomodulatory properties and can be found in the cerebrospinal fluid (CSF); however, their actions have not been studied in bacterial meningitis. We investigated the association between CSF sex steroid hormone levels and inflammatory parameters, disease severity, and outcome in pneumococcal meningitis. We identified adults with culture-proven pneumococcal meningitis in a prospective cohort study (2006-2014). We measured estradiol and testosterone in CSF using liquid chromatography-tandem mass spectrometry and sex hormone-binding globulin (SHBG) using an enzyme-linked immunoassay. Hormone levels were compared according to outcome, which was graded using the Glasgow Outcome Scale (a score of 5 indicating favorable, 1-4 unfavorable outcome). Correlation analysis was used to measure the association between hormone levels and inflammatory cytokines, chemokines, and complement factors as well as severity of illness, as measured by the Glasgow Coma Scale and the Dutch Meningitis Risk Score. We included 60 patients: 20 men, 20 premenopausal (50 years) women. Twenty-one (35%) patients had an unfavorable outcome and 11 (18%) died. Cases with an unfavorable outcome exhibited higher estradiol (median 14.0 vs 5.0 pmol/L, P = .04) and lower SHBG (0.40 vs 1.0 nmol/L, P = .03) levels compared with those with a favorable outcome. Estradiol was positively correlated with C-reactive protein (R = 0.42, P = .001), CSF protein (R = 0.33, P = .01), and proinflammatory cytokine levels. CSF concentrations of the sex steroid hormone estradiol were associated with outcome and CSF inflammation. Understanding the dose and time-dependent interaction between sex steroid hormones and the inflammatory response in bacterial meningitis represents an important and understudied topic.info:eu-repo/semantics/publishedVersio

Defect-unbinding and the Bose-glass transition in layered superconductors

The low-field Bose-glass transition temperature in heavy-ion irradiated Bi_2Sr_2CaCu_2O_8+d increases progressively with increasing density of irradiation-induced columnar defects, but saturates for densities in excess of 1.5 x10^9 cm^-2. The maximum Bose-glass temperature corresponds to that above which diffusion of two-dimensional pancake vortices between different vortex lines becomes possible, and above which the ``line-like'' character of vortices is lost. We develop a description of the Bose-glass line that is in excellent quantitative agreement with the experimental line obtained for widely different values of track density and material parameters.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let

Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis.

Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (-794 CATT5-8; rs5844572) and a single-nucleotide polymorphism (-173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and -173 C high-expression MIF alleles were associated with unfavorable outcome (P= 0.005 and 0.003) and death (P= 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P= 0.02] and carriage of the CATT7 allele (OR 5.12,P= 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P= 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy

High rates of suicide and attempted suicide using pesticides in Nickerie, Suriname, South America

Suicide and attempted suicide are identified as a serious mental health problem in Suriname, especially in the district of Nickerie. An epidemiological study in the Nickerie catchment area revealed high rates of suicide (48 per 100,000) and attempted suicide (207 per 100,000) on average in the years 2000–2004. Particularly remarkable is the high number of attempted suicides among males (49%), and the use of pesticides in both fatal (55%) and nonfatal suicidal behavior (44%). Probably this high incidence of suicidal behavior reflects the very poor economic situation of the district, poverty of most of the population, high levels of alcohol misuse, domestic violence, the rigidity of Hindustani culture regarding family traditions, the accessibility of pesticides, and the lack of future perspectives. Health care alone will not be sufficient to tackle this problem. One of the most urgent measures to prevent suicides is to stow away pesticides in locked cabinets with the key held by the proprietor

The magnetization of PrFeAsO0.60_{0.60}F$_{0.12} sueprconductor

The magnetization of the PrFeAsO$_{0.60}$F$_{0.12}$ polycrystalline sample has been measured as functions of temperature and magnetic field $(H)$. The observed total magnetization is the sum of a superconducting irreversible magnetization ($M_s$) and a paramagnetic magnetization ($M_p$). Analysis of dc susceptibility $\chi(T)$ in the normal state shows that the paramagnetic component of magnetization comes from the Pr$^{+3}$ magnetic moments. The intragrain critical current density $(J_L)$ derived from the magnetization measurement is large. The $J_L(H)$ curve displays a second peak which shifts towards the high-field region with decreasing temperature. In the low-field region, a plateau up to a field $H^*$ followed by a power law $H^{-5/8}$ behavior of $J_L(H)$ is the characteristic of the strong pinning. A vortex phase diagram for the present superconductor has been obtained from the magnetization and resistivity data.Comment: A revised version with modified title,8 pages, 7 figure

Microwave Surface-Impedance Measurements of the Magnetic Penetration Depth in Single Crystal Ba1-xKxFe2As2 Superconductors: Evidence for a Disorder-Dependent Superfluid Density

We report high-sensitivity microwave measurements of the in-plane penetration depth $\lambda_{ab}$ and quasiparticle scattering rate $1/\tau$ in several single crystals of hole-doped Fe-based superconductor Ba$_{1-x}$K$_x$Fe$_2$As$_2$ ($x\approx 0.55$). While power-law temperature dependence of $\lambda_{ab}$ with the power $\sim 2$ is found in crystals with large $1/\tau$, we observe exponential temperature dependence of superfluid density consistent with the existence of fully opened two gaps in the cleanest crystal we studied. The difference may be a consequence of different level of disorder inherent in the crystals. We also find a linear relation between the low-temperature scattering rate and the density of quasiparticles, which shows a clear contrast to the case of d-wave cuprate superconductors with nodes in the gap. These results demonstrate intrinsically nodeless order parameters in the Fe-arsenides.Comment: 4 pages, 4 figures, 1 table. Accepted for publication in Phys. Rev. Lett. Changed title as suggested by the PRL editor

Specifying and Analysing SOC Applications with COWS

COWS is a recently defined process calculus for specifying and combining service-oriented applications, while modelling their dynamic behaviour. Since its introduction, a number of methods and tools have been devised to analyse COWS specifications, like e.g. a type system to check confidentiality properties, a logic and a model checker to express and check functional properties of services. In this paper, by means of a case study in the area of automotive systems, we demonstrate that COWS, with some mild linguistic additions, can model all the phases of the life cycle of service-oriented applications, such as publication, discovery, negotiation, orchestration, deployment, reconfiguration and execution. We also provide a flavour of the properties that can be analysed by using the tools mentioned above

Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis

Timing and mechanism of the rise of the Shillong Plateau in the Himalayan foreland

The Shillong Plateau (northeastern India) constitutes the only significant topography in the Himalayan foreland. Knowledge of its surface uplift history is key to understanding topographic development and unraveling tectonic–climate–topographic coupling in the eastern Himalaya. We use the sedimentary record of the Himalayan foreland basin north of the Shillong Plateau to show that the paleo-Brahmaputra river was redirected north and west by the rising plateau at 5.2–4.9 Ma. We suggest that onset of plateau uplift is a result of increased fault-slip rates in response to stresses caused by the Indian lithosphere bending beneath the Himalaya