Optimal doses of rifampicin in the standard drug regimen to shorten tuberculosis treatment duration and reduce relapse by eradicating persistent bacteria.

Objectives: Although high-dose rifampicin holds promise for improving tuberculosis disease control by eradication of persistent bacteria, the optimal dose of rifampicin that kills persistent bacteria and shortens the treatment duration is unknown. Methods: The Cornell mouse model was used to test the efficacy of rifampicin at elevated doses combined with isoniazid and pyrazinamide to kill actively growing and persistent bacilli and to measure relapse rate. Persistent bacteria were evaluated using Mycobacterium tuberculosis culture supernatant containing resuscitation-promoting factors. Pharmacokinetic parameters and dose-dependent activity for cultivable and persistent bacilli were determined. Results: Increasing doses of rifampicin in combination with isoniazid and pyrazinamide resulted in dose-dependent faster bacterial clearance. Evaluated both on solid media and in culture filtrate containing resuscitation-promoting factors, a regimen containing a standard dose of rifampicin at 10 mg/kg over 14 weeks failed to achieve organ sterility. In contrast, higher doses of rifampicin achieved organ sterility in a much shorter time of 8-11 weeks. Disease relapse, which occurred in 86% of mice treated with the standard regimen for 14 weeks, was completely prevented by rifampicin doses of ≥ 30 mg/kg. Conclusions: In the treatment of murine tuberculosis, a rifampicin dose of 30 mg/kg was sufficient to eradicate persistent M. tuberculosis, allowing shorter treatment duration without disease relapse

Investigation of elimination rate, persistent subpopulation removal and relapse rates of Mycobacterium tuberculosis by combinations of first-line drugs in a modified Cornell mouse model.

Currently, the most effective tuberculosis control method resides in case-finding and 6 months chemotherapy. There is a need to improve our understanding about drug interactions, combination activities and the ability to remove persistent bacteria in the current regimens, particularly in relation to relapse. We aimed to investigate the therapeutic effects of three main components, rifampicin (RMP), isoniazid (INH), and pyrazinamide (PZA), in current drug regimens using a modified version of the Cornell mouse model. We evaluated the post-treatment levels of persistent Mycobacterium tuberculosis in the organs of mice using culture filtrate derived from M. tuberculosis strain H37Rv. When RMP was combined with INH, PZA or INH-PZA, significant additive activities were observed compared to each of the single drug treatments. However, the combination of INH and PZA showed a less significant additive effect than either of the drugs used on their own. Apparent culture negativity of mouse organs was achieved at 14 weeks of treatment with RMP-INH, RMP-PZA and RMP-INH-PZA but not with INH-PZA, when conventional tests, namely culture on solid agar and in liquid broth indicated that the organs were bacteria negative. The relapse rates for RMP-containing regimens were not significantly different to a 100% relapse rate at the numbers of mice examined in this study. In parallel, we examined the organs for the presence of culture filtrate-dependent persistent bacilli after 14 weeks of treatment. Culture filtrate treatment of the organs revealed persistent M. tuberculosis Modelling of mycobacterial elimination rates and evaluation of culture-filtrate dependent organisms showed promise as surrogate methods for efficient factorial evaluation of drug combinations in tuberculosis in mouse models and should be further evaluated against relapse. The presence of culture filtrate-dependent persistent M. tuberculosis is the likely cause of disease relapse in this modified Cornell mouse model

Magnetic and structural characterization of thiol capped ferromagnetic Ag nanoparticles

Dodecanethiol capped Ag nanoparticles (NPs) have been independently synthesized by the well-known Brust method under the same physical-chemical conditions. The obtained NP present similar sizes ( ∼ 2 nm) but different magnetic behaviors. The extended x-ray absorption fine structure analyses at the K-edge of Ag did not reveal any noticeable structural nor topological differences among the samples. In clear contrast with the structure provided for thiol capped ferromagnetic Au NPs, the analysis also brings out the existence of Ag–S bonds in a diffuse region surrounding a reduced Ag core where the magnetism of the Ag NPs would be located. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Alcohol consumption and risky sexual practices: the pattern of nursing students from the Spanish University

OBJECTIVE: to determine the prevalence of substance abuse and unsafe sexual practices and to analyze the relationship between them, in nursing students at the University of Seville. METHOD: quantitative methodological approach with a descriptive cross-sectional design. The population was composed of first year nursing students in the University of Seville, during the academic year 2010-2011 (N=510), with consecutive opportunistic sampling composed of students who attended class on the scheduled day (n=291). RESULTS: a high prevalence of alcohol consumption, and increased likelihood of not using protective measures during sexual practices when alcohol had been consumed, was present. CONCLUSION: these findings are consistent with those obtained in the same population in Brazil, and highlight the need to strengthen in the nursing curriculum, the transverse axis related to the prevention of substance abuse, especially alcohol

Comparación de distintas estrategias para la predicción de muerte a corto plazo en el paciente anciano infectado

Objective. The aim of this study was to determine the utility of a post hoc lactate added to SIRS and qSOFA score to predict 30-day mortality in older non-severely dependent patients attended for infection in the Emergency Department (ED). Methods. We performed an analytical, observational, prospective cohort study including patients of 75 years of age or older, without severe functional dependence, attended for an infectious disease in 69 Spanish ED for 2-day three seasonal periods. Demographic, clinical and analytical data were collected. The primary outcome was 30-day mortality after the index event. Results. We included 739 patients with a mean age of 84.9 (SD 6.0) years; 375 (50.7%) were women. Ninety-one (12.3%) died within 30 days. The AUC was 0.637 (IC 95% 0.587-0.688; p= 2 and 0.698 (IC 95% 0.635- 0.761; p= 2. Comparing receiver operating characteristic (ROC) there was a better accuracy of qSOFA vs SIRS (p=0.041). Both scales improve the prognosis accuracy with lactate inclusion. The AUC was 0.705 (IC95% 0.652-0.758; p<0.001) for SIRS plus lactate and 0.755 (IC95% 0.696-0.814; p<0.001) for qSOFA plus lactate, showing a trend to statistical significance for the second strategy (p=0.0727). Charlson index not added prognosis accuracy to SIRS (p=0.2269) or qSOFA (p=0.2573). Conclusions. Lactate added to SIRS and qSOFA score improve the accuracy of SIRS and qSOFA to predict short-term mortality in older non-severely dependent patients attended for infection. There is not effect in adding Charlson index

Precise Size Control of the Growth of Fe3O4 Nanocubes over a Wide Size Range Using a Rationally Designed One-Pot Synthesis

The physicochemical properties of spinel oxide magnetic nanoparticles depend critically on both their size and shape. In particular, spinel oxide nanocrystals with cubic morphology have shown superior properties in comparison to their spherical counterparts in a variety of fields, like, for example, biomedicine. Therefore, having an accurate control over the nanoparticle shape and size, while preserving the crystallinity, becomes crucial for many applications. However, despite the increasing interest in spinel oxide nanocubes there are relatively few studies on this morphology due to the difficulty to synthesize perfectly defined cubic nanostructures, especially below 20 nm. Here we present a rationally designed synthesis pathway based on the thermal decomposition of iron(III) acetylacetonate to obtain high quality nanocubes over a wide range of sizes. This pathway enables the synthesis of monodisperse Fe3O4 nanocubes with edge length in the 9-80 nm range, with excellent cubic morphology and high crystallinity by only minor adjustments in the synthesis parameters. The accurate size control provides evidence that even 1-2 nm size variations can be critical in determining the functional properties, for example, for improved nuclear magnetic resonance T2 contrast or enhanced magnetic hyperthermia. The rationale behind the changes introduced in the synthesis procedure (e.g., the use of three solvents or adding Na-oleate) is carefully discussed. The versatility of this synthesis route is demonstrated by expanding its capability to grow other spinel oxides such as Co-ferrites, Mn-ferrites, and Mn3O4 of different sizes. The simplicity and adaptability of this synthesis scheme may ease the development of complex oxide nanocubes for a wide variety of applications

Spanish nationalism: ethnic or civic?

ABSTRACT In recent years, it has been a common complaint among scholars to acknowledge the lack of research on Spanish nationalism. This article addresses the gap by giving an historical overview of ‘ethnic ’ and ‘civic ’ Spanish nationalist discourses during the last two centuries. It is argued here that Spanish nationalism is not a unified ideology but it has, at least, two varieties. During the 19th-century, both a ‘liberal ’ and a ‘conservative-traditionalist ’ nationalist discourse were formu-lated and these competed against each other for hegemony within the Spanish market of ideas. In the 20th-century, these two discourses continued to be present and became backbones of different political regimes. However, after the emergence of the Basque and Catalan nationalist movements, Spanish nationalists unified as a counter-force to these regional sources of identity. In fact, one can see 20th-century Spanish nationalism as a dialectical struggle between the centre and the periphery