In vitro antimicrobial efficacy of a fixed-dose combination of RHZE against M. tuberculosis

The use of drugs in fixed-dose combination (FDC) is now recommended by the World Health Organization (WHO) due to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis. FDC uses different drugs against tuberculosis (TB) in a single tablet for phase-intensive therapeutic intervention. This therapy aims to optimize treatment, to prevent inappropriate use of drugs, and to prevent the emergence of new resistant strains. This study aims to evaluate the susceptibility of clinical isolates of M. tuberculosis against rifampicin, isoniazid, ethambutol, and pyrazinamide. The antimicrobials were tested separately and in associations according to FDC. This was used for broth microdilution method, which was compared to the proportions method previously considered as the gold standard. In antimicrobials testing alone, several strains were resistant to one, two, or three drugs. However, when applied to association of drugs in FDC, there was no antimicrobial resistance. The results strengthen the FDC's concept, which aims to unite the four anti-TB drugs to combat bacterial resistance

Fármacos Anticorpos Monoclonais para o Tratamento do Câncer: uma Perspectiva Brasileira

Introdução: Os anticorpos monoclonais (mAb) são alternativa terapêutica importante no tratamento do câncer. Porém, o acesso a essa terapia é desigual entre países com diferentes rendas. Objetivo: Comparar os fármacos mAb aprovados para uso contra câncer nos EUA com os aprovados no Brasil e discutir, por meio do mecanismo de ação, alternativas terapêuticas disponíveis. Método: A lista de fármacos mAb aprovados pelo FDA foi coletada de publicação prévia e complementada com dados presentes no site dessa agência, assim como mecanismo de ação, data de aprovação e indicações clínicas foram obtidos das bulas dos medicamentos nesse mesmo site. Da mesma forma, os dados de data de aprovação pela Anvisa foram obtidos em consultas ao site dessa agência. Os fármacos foram tabelados e organizados conforme características estruturais e separados em quatro grandes grupos, conforme seu mecanismo de ação. Resultados: Até 2022, 48 mAb foram aprovados para uso contra o câncer pelo FDA. Destes, 37 foram aprovados pela Anvisa para uso no Brasil, com tempo médio entre aprovação no exterior e no Brasil próximo a dois anos. A maioria dos mAb são humanos ou humanizados (77%) e variam bastante com relação ao mecanismo de ação, sendo o antígeno de linfócitos B CD20 e o checkpoint imunológico PD-1/PD-L1 os principais alvos dos mAb avaliados. Conclusão: Apesar de alguns fármacos aprovados no exterior ainda não estarem aprovados no Brasil, o atraso para registro não parece estar relacionado à demora da Anvisa. Além disso, para a maioria dos casos de fármacos ainda não aprovados no Brasil, existem alternativas terapêuticas disponíveis.

Evaluation of bedtime vs. morning levothyroxine intake to control hypothyroidism in older patients : a pragmatic crossover randomized clinical trial

Introduction: Drug scheduling in older adults can be a challenge, especially considering polypharmacy, physical dependency, and possible drug interactions. Properly testing alternative treatment regimens could therefore help to overcome treatment barriers. Hypothyroidism is a prevalent condition in older adults, however, studies evaluating Lthyroxine treatment effectiveness in this specific age group are still lacking. Most studies testing an evening administration of levothyroxine were mainly composed of younger adults. Therefore, this trial is aimed to assess if evening levothyroxine (LT4) administration can effectively control hypothyroidism in older patients. Materials and Methods: A randomized crossover clinical trial was conducted between June 2018 and March 2020 at the Hospital de Clínicas de Porto Alegre, a teaching hospital in Brazil, to compare the efficacy of morning and evening administration of LT4 for hypothyroidism control in older patients. The study protocol is published elsewhere. A total of 201 participants, ≥60 years old, with primary hypothyroidism treated with LT4 for at least 6 months and on stable doses for at least 3 months were included. Participants were randomly assigned to a starting group of morning LT4 intake (60min before breakfast) or bedtime LT4 intake (60min after the last meal). After ≥12 weeks of follow-up, a crossover between strategies was performed. The primary outcome was the change in serum thyrotropin (Thyroid-Stimulating Hormone; TSH) levels after 12 weeks of each LT4 administration regimen. Results: A total of 201 participants with mean age of 72.4 ± 7.2 years were included, out of which 84.1% were women; baseline characteristics and frequency of controlled hypothyroidism were similar between groups. Mean baseline TSH was 3.43 ± 0.25 mUI/L. In total, 118 participants attended three meetings, allowing 135 comparisons by crossover analytic strategy. Mean TSH levels after follow-up were 2.95 ± 2.86 in the morning group and 3.64 ± 2.86 in the bedtime group, p = 0.107. Discussion: Thyroid-Stimulating Hormone levels and frequency of controlled hypothyroidism were similar during the follow-up period regardless of the treatment regimen (morning or bedtime)

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio