HIV-1 co/super-infection in intravenous drug users.

BACKGROUND: The frequency of HIV-1 co/super-infection is unknown despite their implications for public health and vaccine development. This issue was addressed during an epidemic of both CRF11 and B subtype among intravenous drug users (IVDUs). METHODS: Bulk sequencing of reverse transcriptase, protease and C2V3 regions and subtype-specific nested polymerase chain reaction (PCR) in plasma and proviral DNA were performed using baseline and follow-up samples collected in recently infected IVDUs between 1998-2002 and in IVDUs with chronic infection living in the same area and presenting an unexpected rise of viremia (> 1 log10). RESULTS: In 58 recently infected patients, three B/CRF-11 co-infections, 25 B, 28 CRF-11 and two other subtypes were detected at baseline. In the three co-infected patients, both CRF-11 and B were detected in plasma and proviral DNA and persisted during follow-up. B- and CFR-11-specific PCR performed on follow-up samples of 40 of 58 recently infected patients (median follow-up, 14.5 months) revealed a transient B super-infection in a patient initially infected by CRF-11. Five of 156 chronic IVDUs (total follow-up: 346 years) had an unexpected rise of viremia. In two of them, aviremic without treatment for years after an initial B infection, a symptomatic CRF-11 super-infection occurred and was associated with high viral load and a fall of CD4 cell count. CONCLUSIONS: In recently infected IVDUs, co-infection B/CRF-11 is relatively frequent (5%). In chronically infected IVDUs super-infection may be transient and may occur in patients controlling efficiently HIV infection by the initial strain.

Iron supplementation in a large Swiss cohort of IBD patients demonstrates a shift from oral to intravenous iron over time

Background: The 2007 European Crohn's and Colitis Organization guidelines on anemia in inflammatory bowel disease (IBD) favour intravenous (iv) over oral (po) iron supplementation due to better effectiveness and tolerance. We aimed to determine the percentage of IBD patients under iron supplementation therapy and the dynamics of prescription habits (iv versus po) over time. Methods: Helsana, a leading Swiss health insurance company provides coverage for approximately 18% of the Swiss population, corresponding to about 1.2 million enrollees. Patients with Crohn's disease (CD) and ulcerative colitis (UC) were analyzed from the anonymised Helsana database. Results: In total, 629 CD (61% female) and 398 UC (57% female) patients were identified, mean observation time was 31.8 months for CD and 31.0 months for UC patients. Of the entire study population, 27.1% were prescribed iron (21.1% in males and 31.1% in females). Patients treated with IBDspecific drugs (steroids, immunomodulators, anti-TNF agents) were more frequently treated with iron compared to patients without any medication (35.0% vs. 20.9%, OR 1.91, 95%- CI 1.41 2.61). The prescription of iv iron increased from 2006/2007 (48.8% of all patients receiving any iron priscription) to 65.2% in 2008/2009 by a factor of 1.89. Conclusions: One third of the IBD population was treated with iron supplementation. A gradual shift from oral to iv iron was observed over time. This switch in prescription habits goes along with the implementation of the ECCO consensus guidelines on anemia in IBD.

Nuclear well logging in soils. Calibration of slim hole nuclear tools gamma-gamma and neutron-thermal neutron.

The calculation of elasticity parameters by sonic and ultra sonic wave propagation in saturated soils using Biot's theory needs the following variables : forpiation density and porosity (p, ø), compressional and shear wave velocities (Vp, Vs), fluid density, viscosity and compressibility (Pfi Ilfi Ki), matrix density and compressibility (p" K), The first four parameters can be determined in situ using logging probes. Because fluid and matrix characteristics are not modified during core extraction, they can be obtained through laboratory measurements. All parameters necessitate precise calibrations in various environments and for specific range of values encountered in soils. The slim diameter of boreholes in shallow geophysics and the high cost of petroleum equipment demand the use of specific probes, which usually only give qualitative results. The measurement 'of density is done with a gamma-gamma probe and the measurement of hydrogen index, in relation to porosity, by a neutron probe. The first step of this work has been carried out in synthetic formations in the laboratory using homogeneous media of known density and porosity. To establish borehole corrections different casings have been used. Finally a comparison between laboratory and in situ data in cored holes of known geometry and casing has been performed.

Fat poetry: a kingdom for PPAR gamma.

Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARgamma agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARgamma in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARgamma modulators.

Influence of arterial occlusion on outcome after intravenous thrombolysis for acute ischemic stroke

BACKGROUND AND PURPOSE: We aimed to assess the interaction between intravenous thrombolysis (IVT) and arterial occlusion on acute cervicocerebral computed tomographic angiography on the outcome of patients with acute ischemic stroke. METHODS: Patients from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry with onset-to-door-time ≤4 hours, acute cervicocerebral computed tomographic angiography, a premorbid modified Rankin Scale ≤2, and a National Institute of Health Stroke Scale (NIHSS) >4 were selected. Patients with significant intracranial arterial obstruction (≥50%-99%) and undergoing acute endovascular treatment were excluded. An interaction analysis of IVT and initial arterial occlusion for favorable 3 months outcome (modified Rankin Scale <3) were performed with adjustment for potential confounders. RESULTS: Among 654 included patients, 382 (58%) showed arterial occlusion, of whom 263 (69%) received IVT. Two hundred seventy-two showed no/minimal obstruction of whom 139 (51%) received IVT. In the adjusted interaction analysis, there was a trend in favor of the arterial occlusion group (odds ratio [OR]=3.97; 95% confidence interval [CI], 0.83-18.97; P=0.08). IVT (versus no IVT) was associated with better outcome in patients with occlusion (adjusted OR for favorable outcome, 3.01; 95% CI, 1.10-8.28) but not in patients with no/minimal obstruction (OR, 0.76; 95% CI, 0.21-2.74). Conversely, patients with occlusion had a similar rate of favorable outcome as no/minimal obstruction when thrombolysed (OR, 0.5; 95% CI, 0.17-1.47) but had a less favorable outcome without thrombolysis (OR, 0.13; 95% CI, 0.04-0.44). CONCLUSIONS: In this retrospective analysis of consecutive patients with acute ischemic stroke, there was a trend for more favorable outcomes with IVT in the setting of initial arterial occlusion than in the setting of no/minimal obstruction. Before confirmation in randomized controlled studies, this information should not influence thrombolysis decisions, however.

The murine interleukin-2 receptor gamma chain gene: organization, chromosomal localization and expression in the adult thymus.

Defects in the interleukin-2 receptor gamma (IL-2R gamma) chain in the man result in an X-linked severe combined immunodeficiency, SCIDX1, characterized by an absence of T-cell differentiation. This phenotype may result from pertubations in IL-2, IL-4-, IL-7- or IL-15-mediated signaling, as the IL-2R gamma chain forms an integral component of these receptor systems. We have isolated and characterized cDNA and genomic clones for the murine IL-2R gamma. The gene (Il2rg) is well conserved between mouse and man with respect to overall structure and size, and contains regions of high conservation in the promoter region as well. Il2rg maps to mouse X chromosome region 40, in a region of synteny with human Xq12-13.1. We have also explored the expression of the IL-2R gamma during thymocyte development. IL-2R gamma transcripts are detected in the earliest thymocyte precursor cells and persist throughout intrathymic development into the mature peripheral compartment. Genomic clones for the murine IL-2R gamma will allow for further studies on the regulation and function of this gene in vivo.

Role of high normal gamma-glutamyltransferase level in identifying heavy alcohol use in young men.

The objective of the current study was to determine the predictive value of high normal gamma-glutamyltransferase (GGT) level as an indication of heavy drinking in young men. In a sample of 577 men attending a one-day army recruitment process mandatory for all Swiss men at age 19 years, GGT level was evaluated as the dependent variable for each of eight dichotomous classifications of individuals on the basis of meeting cut-off criteria for five indexes of alcohol use, two indexes of alcohol-related problems, and one index of body mass. The sensitivity, specificity, and predictive values of GGT level in identifying subjects as either heavy drinkers or being overweight were determined. Compared with findings for their counterparts, GGT level was higher in subjects reporting consumption of more than 14 drinks per week (20.5 +/- 7.81 vs. 18.9 +/- 7.60, P <.05), in those reporting being drunk at least once during the past 30 days (20.3 +/- 7.80 vs. 18.3 +/- 7.43, P <.001), and in individuals with body mass indexes >or=25 kg/m(2) (25.8 +/- 10.84 vs. 18.3 +/- 6.59, P <.001). At a GGT level cut-off of 20 U/l, the sensitivity, specificity, and positive and negative predictive values of either being a heavy drinker or overweight were 48.2%, 70.2%, 67.7%, and 51.2%, respectively. Exclusion of subjects with body mass indexes of >or=25 kg/m(2) revealed similar results. High normal GGT level in young men is indicative of heavy alcohol use or being overweight; when present, subjects should be screened further for potential concomitant drinking problems.

A numerical model for the gamma-ray emission of the microquasar LS 5039

The possible association between the microquasar LS 5039 and the EGRET source 3EG J1824-1514 suggests that microquasars could also be sources of high energy gamma-rays. In this paper, we explore, with a detailed numerical model, if this system can produce the emission detected by EGRET (>100 MeV) through inverse Compton (IC) scattering. Our numerical approach considers a population of relativistic electrons entrained in a cylindrical inhomogeneous jet, interacting with both the radiation and the magnetic fields, taking into account the Thomson and Klein-Nishina regimes of interaction. The computed spectrum reproduces the observed spectral characteristics at very high energy.

Microquasars as high energy gamma-ray sources

Galactic microquasars are certainly one of the most recent additions to the field of high energy astrophysics and have attracted increasing interest over the last decade. However, the high energy part of the spectrum of microquasars is the most poorly known, mainly due the lack of sensitive instrumentation in the past. Microquasars are now primary targets for all of the observatories working in the X-ray and gamma-ray domains. They also appear as the possible counterparts for some of the unidentified sources of high-energy gamma-rays detected by the experiment EGRET on board the satellite COMPTON-GRO. This paper provides a general review of the main observational results obtained up to now as well as a summary of the scenarios for production of high-energy gamma-rays at the present moment.

High-energy gamma-ray emission from microquasars: LS 5039 and LS I+61303

The possible associations between the microquasars LS 5039 and LS I +61 303 and the EGRET sources 3EG J1824-1514 and 3EG J0241+6103 suggest that microquasars could also be sources of high-energy gamma-rays. In this work, we present a detailed numerical inverse Compton (IC) model, based on a microquasar scenario, that reproduces the high-energy gamma-ray spectra and variability observed by EGRET for the mentioned sources. Our model considers a population of relativistic electrons entrained in a cylindrical inhomogeneous jet that interact through IC scattering with both the radiation and the magnetic fields.

Search for very high energy gamma-ray emission from pulsar-pulsar wind nebula systems with the MAGIC telescope

The MAGIC collaboration has searched for high-energy gamma-ray emission of some of the most promising pulsar candidates above an energy threshold of 50 GeV, an energy not reachable up to now by other ground-based instruments. Neither pulsed nor steady gamma-ray emission has been observed at energies of 100 GeV from the classical radio pulsars PSR J0205+6449 and PSR J2229+6114 (and their nebulae 3C58 and Boomerang, respectively) and the millisecond pulsar PSR J0218+4232. Here, we present the flux upper limits for these sources and discuss their implications in the context of current model predictions.

Ex vivo analysis of human antigen-specific CD8+ T-cell responses: quality assessment of fluorescent HLA-A2 multimer and interferon-gamma ELISPOT assays for patient immune monitoring.

The authors developed a standardized approach for immune monitoring of antigen-specific CD8+ T cells within peripheral blood lymphocytes (PBLs) that combines direct ex vivo analysis of Melan-A/MART-1 and influenza-specific CD8+ T cells with HLA-A2/peptide multimers and interferon-gamma ELISPOT assays. Here the authors assessed the quality of results obtained with 180 PBLs from healthy donors and melanoma patients. Reproducibility of the multimer assay was good (average of 15% variation). In the absence of in vivo antigen-specific T-cell responses, physiologic fluctuations of multimer-positive T cells was low, with variation coefficients of 20% for Melan-A and 28% for influenza-specific T cells. In contrast, patients with vaccination-induced T-cell responses had significantly increased T-cell frequencies clearly exceeding physiologic fluctuations. Comparable results were obtained with ELISPOT assays. In conclusion, this approach is well suited to assess T-cell responses as biologic endpoints in clinical vaccine studies.

The optimal dividend barrier in the Gamma-Omega model

In the traditional actuarial risk model, if the surplus is negative, the company is ruined and has to go out of business. In this paper we distinguish between ruin (negative surplus) and bankruptcy (going out of business), where the probability of bankruptcy is a function of the level of negative surplus. The idea for this notion of bankruptcy comes from the observation that in some industries, companies can continue doing business even though they are technically ruined. Assuming that dividends can only be paid with a certain probability at each point of time, we derive closed-form formulas for the expected discounted dividends until bankruptcy under a barrier strategy. Subsequently, the optimal barrier is determined, and several explicit identities for the optimal value are found. The surplus process of the company is modeled by a Wiener process (Brownian motion).