Alterations in prefrontal-limbic functional activation and connectivity in chronic stress-induced visceral hyperalgesia.

Repeated water avoidance stress (WAS) induces sustained visceral hyperalgesia (VH) in rats measured as enhanced visceromotor response to colorectal distension (CRD). This model incorporates two characteristic features of human irritable bowel syndrome (IBS), VH and a prominent role of stress in the onset and exacerbation of IBS symptoms. Little is known regarding central mechanisms underlying the stress-induced VH. Here, we applied an autoradiographic perfusion method to map regional and network-level neural correlates of VH. Adult male rats were exposed to WAS or sham treatment for 1 hour/day for 10 days. The visceromotor response was measured before and after the treatment. Cerebral blood flow (CBF) mapping was performed by intravenous injection of radiotracer ([(14)C]-iodoantipyrine) while the rat was receiving a 60-mmHg CRD or no distension. Regional CBF-related tissue radioactivity was quantified in autoradiographic images of brain slices and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. Compared to sham rats, stressed rats showed VH in association with greater CRD-evoked activation in the insular cortex, amygdala, and hypothalamus, but reduced activation in the prelimbic area (PrL) of prefrontal cortex. We constrained results of seed correlation analysis by known structural connectivity of the PrL to generate structurally linked functional connectivity (SLFC) of the PrL. Dramatic differences in the SLFC of PrL were noted between stressed and sham rats under distension. In particular, sham rats showed negative correlation between the PrL and amygdala, which was absent in stressed rats. The altered pattern of functional brain activation is in general agreement with that observed in IBS patients in human brain imaging studies, providing further support for the face and construct validity of the WAS model for IBS. The absence of prefrontal cortex-amygdala anticorrelation in stressed rats is consistent with the notion that impaired corticolimbic modulation acts as a central mechanism underlying stress-induced VH

Observational epidemiological study to identify the clinical profile of naïve patients starting antiretroviral (ARV) therapy in Spain

Purpose of the study: To identify the proportion of patients starting ARV treatment with NNRTIs or with a PI/r and to explore and compare their clinical profile establishing different factors whereby physicians select the initial ARV treatment in a Spanish clinical setting. Methods: An observational study was conducted in two different phases. In Phase I a cross-sectional registration was conducted for patients who initiated ARV treatment in a 6-month period in 65 Spanish hospitals. In Phase II clinical and social-demographic features were collected retrospectively of patients who visited HIV clinics between August and November 2010 who had started ARV treatment containing an NNRTIs or a PI/r in Phase I. Summary of results: In Phase I, 1,687 subjects who initiated ARV treatment were registered, of which 53% started with an NNRTI-based regimen whereas 42% started with a PI/r-based regimen. Two percent of the treatment initiations occurred in a clinical trial. In Phase II, 642 patients were paired consecutively and retrospectively. The group of patients was composed of predominantly male subjects (81% vs 19%). The median time between diagnosis and the start of ARV treatment was 3.6±5.3 years. At the initiation of treatment, 72% of patients had a CD4 count below 350 cells/µl. Although treatment based on NNRTIs in naïve patients is the most frequent option in Spain, the analysis of clinical profiles shows that PI/r-based therapy is more often used than NNRTIs with statistical significance in patients with high viral load, Fig. A (≥100.000 copies/ml) (58% vs 42%; OR:1,75; 95% CI: 1,26–2,43; p<0,01), with CD4 cell counts <200 cells/µl, Fig. B (68% vs 31%; OR: 2,92; 95% CI: 1,99–4,27; p<0,01), and in patients at CDC stage C (65% vs 35%; OR: 2,05; CI: 1,27–3,31; p<0,01). Conclusions: In Spain, HIV is still diagnosed late (as measured by CD4 count<350 cells/µl). Treatment based on NNRTIs are more frequently used in naïve patients, although PIs/r-based regimens play an important role being the preferred option in patients with high viral load (≥100.000 copies/ml) and low CD4 cell count (<200 cells/µl)

Antagonism between Bacteriostatic and Bactericidal Antibiotics Is Prevalent

Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion of the use of combination therapy requires knowledge of how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal drugs are most potent with actively dividing cells, then the inhibition of growth induced by a bacteriostatic drug should result in an overall reduction of efficacy when the drug is used in combination with a bactericidal drug. Our goal here was to investigate this hypothesis systematically. We first constructed time-kill curves using five different antibiotics at clinically relevant concentrations, and we observed antagonism between bactericidal and bacteriostatic drugs. We extended our investigation by performing a screen of pairwise combinations of 21 different antibiotics at subinhibitory concentrations, and we found that strong antagonistic interactions were enriched significantly among combinations of bacteriostatic and bactericidal drugs. Finally, since our hypothesis relies on phenotypic effects produced by different drug classes, we recreated these experiments in a microfluidic device and performed time-lapse microscopy to directly observe and quantify the growth and division of individual cells with controlled antibiotic concentrations. While our single-cell observations supported the antagonism between bacteriostatic and bactericidal drugs, they revealed an unexpected variety of cellular responses to antagonistic drug combinations, suggesting that multiple mechanisms underlie the interactions

q-Deformed Superalgebras

The article deals with q-analogs of the three- and four-dimensional Euclidean superalgebra and the Poincare superalgebra.Comment: 38 pages, LateX, no figures, corrected typo

Binary Collisions and the Slingshot Effect

We derive the equations for the gravity assist manoeuvre in the general 2D case without the constraints of circular planetary orbits or widely different masses as assumed by Broucke, and obtain the slingshot conditions and maximum energy gain for arbitrary mass ratios of two colliding rigid bodies. Using the geometric view developed in an earlier paper by the authors the possible trajectories are computed for both attractive or repulsive interactions yielding a further insight on the slingshot mechanics and its parametrization. The general slingshot manoeuvre for arbitrary masses is explained as a particular case of the possible outcomes of attractive or repulsive binary collisions, and the correlation between asymptotic information and orbital parameters is obtained in general.Comment: 12 pages, 7 figures, accepted for publication Dec'07, Celestial Mechanics and Dynamical Astronom

Mycobacterium tuberculosis Rv0679c protein sequences involved in host-cell infection: Potential TB vaccine candidate antigen

Hasta la fecha, la función de muchas proteínas de membrana hipotéticas de Mycobacterium tuberculosis aún se desconoce y su participación en las interacciones patógeno-huésped aún no se ha definido claramente. En este estudio, se evaluó la actividad biológica de los péptidos derivados de la proteína de membrana hipotética Rv0679c de M. tuberculosis y su participación en las interacciones patógeno-huésped. La transcripción del gen Rv0679c se estudió en 26 Mycobacteriumspp. Son. Los anticuerpos generados contra los supuestos epítopos de células B de Rv0679c se usaron en ensayos de inmunotransferencia y microscopía inmunoelectrónica. Los péptidos sintéticos que abarcan toda la longitud de la proteína fueron probados por su capacidad para unirse a las células A549 y U937. Los péptidos de unión de alta actividad (HABP) identificados en Rv0679c se probaron para determinar su capacidad para inhibir la invasión de micobacterias en las células.To date, the function of many hypothetical membrane proteins of Mycobacterium tuberculosis is still unknown and their involvement in pathogen-host interactions has not been yet clearly defined. In this study, the biological activity of peptides derived from the hypothetical membrane protein Rv0679c of M. tuberculosis and their involvement in pathogen-host interactions was assessed. Transcription of the Rv0679c gene was studied in 26 Mycobacterium spp. Strains. Antibodies raised against putative B-cell epitopes of Rv0679c were used in Western blot and immunoelectron microscopy assays. Synthetic peptides spanning the entire length of the protein were tested for their ability to bind to A549 and U937 cells. High-activity binding peptides (HABPs) identified in Rv0679c were tested for their ability to inhibit mycobacterial invasion into cells

Checklist of the freshwater fishes of Colombia

Data derived from the literature supplemented by examination of specimens in collections show that 1435 species of native fishes live in the freshwaters of Colombia. These species represent 14 orders and 47 families. Orders with the largest numbers of species in the Colombian continental ichthyofauna are the Characiformes (637 species), Siluriformes (524 species), Perciformes (124 species), and Gymnotiformes (74 species), with the remaining 10 orders having from 1 to 35 species. At the family level, the Characidae has the greatest number of species (399 species), with this followed by the Loricariidae (166 species), Cichlidae (114 species), Pimelodidae (54 species), and Trichomycteridae (54 species); the remaining 42 families having 1 to 52 species. Present data indicate that 311 of the species occur solely at locations within Colombia. Continued descriptions of new species from the continental waters of Colombia demonstrate that the present total underestimates the species-level diversity of the ichthyofauna. The 1435 species living in Colombian freshwaters represent approximately 5% of all freshwater and marine fish species now recognized worldwide and approximately 29% of the freshwater fish species known to inhabit the drainages across the expanse from the southern border of Mexico through to Chile and Argentina. Various historical and ecological factors potentially contributing to the species-level richness of the Colombian freshwater fish fauna are discussed (e.g. geology, climate, physiography, water chemistry)

Simulation of the CMS Resistive Plate Chambers

The Resistive Plate Chamber (RPC) muon subsystem contributes significantly to the formation of the trigger decision and reconstruction of the muon trajectory parameters. Simulation of the RPC response is a crucial part of the entire CMS Monte Carlo software and directly influences the final physical results. An algorithm based on the parametrization of RPC efficiency, noise, cluster size and timing for every strip has been developed. Experimental data obtained from cosmic and proton-proton collisions at $\sqrt{s}=7$ TeV have been used for determination of the parameters. A dedicated validation procedure has been developed. A good agreement between the simulated and experimental data has been achieved.Comment: to be published in JINS