Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase

Objectives (S)-Leucoxine, isolated from the Colombian Lauraceae tree Rhodostemonodaphne crenaticupula Madriñan, was found to inhibit the growth of Mycobacterium tuberculosis H37Rv. A biomimetic approach for the chemical synthesis of a wide array of 1-substituted tetrahydroisoquinolines was undertaken with the aim of elucidating a common pharmacophore for these compounds with novel mode(s) of anti-TB action. Methods Biomimetic Pictet–Spengler or Bischler–Napieralski synthetic routes were employed followed by an evaluation of the biological activity of the synthesized compounds. Results In this work, the synthesized tetrahydroisoquinolines were found to inhibit the growth of M. tuberculosis H37Rv and affect its whole-cell phenotype as well as the activity of the ATP-dependent MurE ligase, a key enzyme involved in the early stage of cell wall peptidoglycan biosynthesis. Conclusions As the correlation between the MIC and the half-inhibitory enzymatic concentration was not particularly strong, there is a credible possibility that these compounds have pleiotropic mechanism(s) of action in M. tuberculosis

A Multiset Rewriting Model for Specifying and Verifying Timing Aspects of Security Protocols

Catherine Meadows has played an important role in the advancement of formal methods for protocol security verification. Her insights on the use of, for example, narrowing and rewriting logic has made possible the automated discovery of new attacks and the shaping of new protocols. Meadows has also investigated other security aspects, such as, distance-bounding protocols and denial of service attacks. We have been greatly inspired by her work. This paper describes the use of Multiset Rewriting for the specification and verification of timing aspects of protocols, such as network delays, timeouts, timed intruder models and distance-bounding properties. We detail these timed features with a number of examples and describe decidable fragments of related verification problems

Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD)

Alpha-1-antitrypsin (AAT) plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD). In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val), PiM2 (Arg101His), PiM3 (Glu376Asp), PiS (Glu264Val) and PiZ (Glu342Lys) SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3) and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms

Brazilian version of the Functional Status Score for the ICU : translation and cross-cultural adaptation

Objetivo: traduzir e adaptar culturalmente a Escala de Estado Funcional em UTI (FSS-ICU - Functional Status Score for the ICU) para o português do Brasil. Métodos: o presente estudo consistiu das seguintes fases: tradução (realizada por dois tradutores independentes), síntese da tradução inicial, tradução de volta ao inglês (realizada por dois tradutores independentes não familiarizados com a FSS-ICU original) e fase de teste, para avaliar a compreensão por parte da audiência alvo. Um comitê de especialistas supervisionou todas as fases e foi responsável pelos ajustes ao longo do processo e pela versão final da tradução. Resultados: a fase de testes incluiu dois fisioterapeutas experientes que avaliaram um total de 30 pacientes críticos (escore da FSS-ICU médio de 25 ± 6). Como os fisioterapeutas não relataram problemas com incertezas ou problemas de interpretação que afetassem seu desempenho, não foram feitos outros ajustes à versão em português brasileiro após a fase de teste. Obteve-se uma boa confiabilidade entre observadores para cada uma das cinco tarefas da FSS-ICU e entre os escores dos dois avaliadores (o coeficiente de correlação intraclasse variou de 0,88 a 0,91). Conclusão: a versão adaptada da FSS-ICU para o português brasileiro comprovou ser de fácil compreensão e aplicação clínica no ambiente da unidade de terapia intensiva.Objective: the aim of the present study was to translate and cross-culturally adapt the Functional Status Score for the intensive care unit (FSS-ICU) into Brazilian Portuguese. Methods: this study consisted of the following steps: translation (performed by two independent translators), synthesis of the initial translation, back-translation (by two independent translators who were unaware of the original FSS-ICU), and testing to evaluate the target audience's understanding. An Expert Committee supervised all steps and was responsible for the modifications made throughout the process and the final translated version. Results: the testing phase included two experienced physiotherapists who assessed a total of 30 critical care patients (mean FSS-ICU score = 25 ± 6). As the physiotherapists did not report any uncertainties or problems with interpretation affecting their performance, no additional adjustments were made to the Brazilian Portuguese version after the testing phase. Good interobserver reliability between the two assessors was obtained for each of the 5 FSS-ICU tasks and for the total FSS-ICU score (intraclass correlation coefficients ranged from 0.88 to 0.91). Conclusion: the adapted version of the FSS-ICU in Brazilian Portuguese was easy to understand and apply in an intensive care unit environment

Measurement of the branching ratios of the decays Xi0 --> Sigma+ e- nubar and anti-Xi0 --> anti-Sigma+ e+ nu

From 56 days of data taking in 2002, the NA48/1 experiment observed 6316 Xi0 --> Sigma+ e- nubar candidates (with the subsequent Sigma+ --> p pi0 decay) and 555 anti-Xi0 --> anti-Sigma+ e+ nu candidates with background contamination of 215+-44 and 136+-8 events, respectively. From these samples, the branching ratios BR(Xi0 --> Sigma+ e- nubar)= (2.51+-0.03stat+-0.09syst)E(-4) and BR(anti-Xi0 --> anti-Sigma+ e+ nu)= (2.55+-0.14stat+-0.10syst)E(-4) were measured allowing the determination of the CKM matrix element |Vus| = 0.209+0.023-0.028. Using the Particle Data Group average for |Vus| obtained in semileptonic kaon decays, we measured the ratio g1/f1 = 1.20+-0.05 of the axial-vector to vector form factors.Comment: 16 pages, 11 figures Submitted to Phys.Lett.

Sedimentary Environment Influences the Effect of an Infaunal Suspension Feeding Bivalve on Estuarine Ecosystem Function

The suspension feeding bivalve Austrovenus stutchburyi is a key species on intertidal sandflats in New Zealand, affecting the appearance and functioning of these systems, but is susceptible to several environmental stressors including sedimentation. Previous studies into the effect of this species on ecosystem function have been restricted in space and time, limiting our ability to infer the effect of habitat change on functioning. We examined the effect of Austrovenus on benthic primary production and nutrient dynamics at two sites, one sandy, the other composed of muddy-sand to determine whether sedimentary environment alters this key species' role. At each site we established large (16 m2) plots of two types, Austrovenus addition and removal. In winter and summer we deployed light and dark benthic chambers to quantify oxygen and nutrient fluxes and measured sediment denitrification enzyme activity to assess denitrification potential. Rates of gross primary production (GPP) and ammonium uptake were significantly increased when Austrovenus was added, relative to removed, at the sandy site (GPP, 1.5 times greater in winter and summer; ammonium uptake, 8 times greater in summer; 3-factor analysis of variance (ANOVA), p<0.05). Denitrification potential was also elevated in Austrovenus addition plots at the sandy site in summer (by 1.6 times, p<0.1). In contrast, there was no effect of Austrovenus treatment on any of these variables at the muddy-sand site, and overall rates tended to be lower at the muddy-sand site, relative to the sandy site (e.g. GPP was 2.1 to 3.4 times lower in winter and summer, respectively, p<0.001). Our results suggest that the positive effects of Austrovenus on system productivity and denitrification potential is limited at a muddy-sand site compared to a sandy site, and reveal the importance of considering sedimentary environment when examining the effect of key species on ecosystem function

Factors associated with delayed diagnosis of tuberculosis in hospitalized patients in a high TB and HIV burden setting: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The most essential components of TB control are early diagnosis and adequate treatment. Delay in the diagnosis and treatment of tuberculosis may result in more extensive disease and more complications, increase severity of the disease and is associated with higher risk of mortality. The purpose of this study was to identify factors associated with delayed diagnosis of TB in hospitalized patients.</p> <p>Methods</p> <p>We conducted a cross-sectional study in a general, tertiary care, university-affiliated hospital. Adult patients with TB that were hospitalized were identified retrospectively, and risk factors for delayed diagnosis were collected.</p> <p>Results</p> <p>The median delay until diagnosis was 6 days (IQR: 2-12 days). One hundred and sixty six (54.4%) patients were diagnosed ≤ 6 days, and 139 (45.6%) > 6 days after admission. The main factors associated with diagnostic delay (> 6 days) were extra-pulmonary TB and negative sputum smear.</p> <p>Conclusions</p> <p>Although hospitalization permits a rapid management of the patient and favors a faster diagnosis, we found an unacceptable time delay before the diagnosis of pulmonary TB was made. Future studies should focus on attempt to explain the reasons of diagnostic retard in the patients with the characteristics related to delay in this study.</p

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Comparing United States and Canadian population exposures from National Biomonitoring Surveys: Bisphenol A intake as a case study

The Centers for Disease Control and Prevention provides biomonitoring data in the United States as part of the National Health and Nutrition Examination Survey (NHANES). Recently, Statistics Canada initiated a similar survey — the Canadian Health Measures Survey (CHMS). Comparison of US and Canadian biomonitoring data can generate hypotheses regarding human exposures from environmental media and consumer products. To ensure that such comparisons are scientifically meaningful, it is essential to first evaluate aspects of the surveys' methods that can impact comparability of data. We examined CHMS and NHANES methodologies, using bisphenol A (BPA) as a case study, to evaluate whether survey differences exist that would hinder our ability to compare chemical concentrations between countries. We explored methods associated with participant selection, urine sampling, and analytical methods. BPA intakes were also estimated to address body weight differences between countries. Differences in survey methods were identified but are unlikely to have substantial impacts on inter-survey comparisons of BPA intakes. BPA intakes for both countries are below health-based guidance values set by the US, Canada and the European Food Safety Authority. We recommend that before comparing biomonitoring data between surveys, a thorough review of methodologic aspects that might impact biomonitoring results be conducted