Synthesis and Anti-Mycobacterium tuberculosis Activity of Imidazo[2,1-b][1,3]oxazine Derivatives against Multidrug-Resistant Strains

The emergence of multidrug-resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC90 values of 0.18–1.63 μM against Mtb H37Rv. Compounds 47–49, 51–53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC90 values below 0.5 μM. In Mtb-infected macrophages, several compounds demonstrated a 1-log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1-b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin-dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1-b][1,3]oxazines and their promising potential against MDR-TB

EFEITO DO TREINAMENTO FÍSICO AERÓBICO EM CORONARIOPATAS SUBMETIDOS A UM PROGRAMA DE REABILITAÇÃO CARDIOVASCULAR

Study Model: Retrospective. Study objectives: Evaluate the effect of aerobic physical training in cardiovascular variables in patients with coronary artery disease participants of a Cardiovascular Rehabilitation Program. Methods: Patients with stable coronary artery disease were included and were analyzed the cardiovascular variables of exercise testing, carried out before and after a minimum period of 12 weeks of aerobic physical training in a Cardiovascular Rehabilitation Program, from February 2002 to July 2005. Results: A significant increment (p <0.0001) of maximal oxygen consumption (VO2 max) was observed after the cardiovascular rehabilitation (30.1 ± 9.5 versus 35.5 ± 8.8 ml/kg/min). The difference of the VO2 max had negative correlation with the initial physical capacity, with greater benefits in patients with smaller initial values of VO2  max. Significant differences were not observed in maximal systolic blood pressure and double product, and a small difference was observed in maximal heart rate. The improvement in ischemic threshold was more pronounced, with an increment of 7.4 ml/kg/min in oxygen consumption, with statistical significance (p < 0.0001) (21.0 ± 6.9 versus 28.4 ± 8.2 ml/kg/min). Conclusions: The cardiovascular rehabilitation improved physical capacity and ischemic threshold in patients participants of a Cardiovascular Rehabilitation Program. The benefit in physical capacity was greater in patients with smaller initial values of maximal oxygen consumption.    Modelo do estudo: Retrospectivo. Objetivos do estudo: Avaliar o efeito do treinamento físico aeróbico nas variáveis cardiovasculares em pacientes coronariopatas participantes do Programa de Reabilitação Cardiovascular. Metodologia: Foram incluídos pacientes portadores de coronariopatia estável e foram avaliadas as variáveis cardiovasculares de testes ergométricos seriados, realizados antes e após um período mínimo de 12 semanas de treinamento físico aeróbico em um Programa de Reabilitação Cardiovascular, de fevereiro de 2002 a julho de 2005. Resultados: Documentou-se incremento significativo (p < 0,0001) do consumo de oxigênio pico (VO2 pico) após a reabilitação cardiovascular (30,1 ± 9,5 versus 35,5 ± 8,8 ml/kg/min). Este delta do VO2 pico apresentou correlação negativa com a capacidade física inicial, com maiores ganhos nos pacientes com menores valores iniciais de VO2 pico. Não foram observadas diferenças significativas na pressão arterial sistólica e no duplo produto pico, e uma diferença de pequena magnitude foi observada na freqüência cardíaca pico. A melhora no limiar isquêmico do miocárdio, avaliada pelo consumo de oxigênio na positivação, foi ainda mais expressiva, com incremento de 7,4 ml/kg/min (p < 0,0001) (21,0 ± 6,9 versus 28,4 ± 8,2 ml/kg/min). Conclusões: A reabilitação cardiovascular melhorou a capacidade física e o limiar isquêmico de pacientes participantes do Programa de Reabilitação Cardiovascular. O benefício na capacidade física foi maior  nos pacientes com menores valores iniciais de consumo de oxigênio pico.   

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO