High mortality from carbapenem-resistant Klebsiella pneumoniae bloodstream infection.

In this study, it was evaluated clinical data of 107 patients with bloodstream infection (BSI) by Klebsiella pneumoniae and performed phenotypic and molecular analyzes in 50.5% (54/107) of the samples, those that showed a resistance profile to carbapenemics. The blaKPC gene was present in 90.4% (49/54) of the samples, blaNDM gene in one sample and, in 7.4% (4/54) of the samples, no carbapenemase gene was found. In the similarity analysis, it was found 4 main clones and 11 samples were not genetically related. The median age of the patients was 58 (40-70) years old and 60.7% (65/107) were male. When comparing two groups of patients with BSI due to K. pneumoniae with and without resistance to carbapenems, the variables ICU permanence, renal failure (IR), previous use of antimicrobials, Charlson's comorbidity index (ICCi), some invasive procedures and death showed a statistically significant difference (p < 0.05). And when relating death as a dependent variable, IR, liver failure and patients with BSI XDR or PDR, were predictors of increased mortality. Our study showed a higher mortality rate in patients with BSI due to carbapenem-resistant pneumonia with additional resistance or not to polymyxins.

Reliability and Learning Effect of the Glittre ADL-Test in Patients with Chronic Obstructive Pulmonary Disease.

The Glittre ADL-test (TGlittre) is a multiple-task test designed to assess functional limitation in patients with chronic obstructive pulmonary disease (COPD). Although few studies have investigated the TGlittre learning effect, the results are still conflicting. This study aimed to investigate the test-retest reliability and learning effect on TGlittre and to identify predicting factors of the learning effect in patients with COPD. Patients performed the TGlittre twice with a 30-minutes resting period between trials. TGlittre consists in measuring the time to complete five laps of a multiple ADL-like activities circuit: walking stairs, carrying a backpack, lifting objects, bending down and rising from a seated position. 124 patients with COPD were assessed [81 men; 66 ± 8 years, forced expiratory volume in one second (FEV1) 37.1 ± 15.0%pred; TGlittre 120 ± 60%pred; six-minute walking test 75.5 ± 17.4%pred]. The time spent in TGlittre presented excellent reliability (ICC = 0.96; 95%CI 0.92 - 0.98; p < 0.001; SEM 0.46 min; MDC 1.28 min) and decreased in the retest (5.24 ± 2.31 min to 4.85 ± 2.02 min; p < 0.001). Patients presented a learning effect of 6.11 ± 11.1% in TGlittre. A lower FEV1 (r2=0.10; p < 0.001) and a worse performance in the first TGlittre (r2=0.28; p < 0.001) are related to the improvement in performance of the second TGlittre. Although the TGlittre is reliable, patients improve their performance when performing the second test probably because they underestimate their functional capacity. These results should encourage professionals to assess TGlittre twice when using this test as an outcome measure.

SARS-CoV-2 vaccine development and how Brazil is contributing.

The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for the development of vaccines. The most advanced strategies have focused on modifications of technologies that were already under development for other viruses, such as SARS, MERS, and even Influenza. Classic and new technologies, such as inactivated and attenuated viruses (non-replicative and replicative), DNA and mRNA vaccines, and nanoparticles containing SARS-CoV-2 antigens, are some of the strategies currently investigated. Although there is a very high expectation for the effectiveness of the most advanced vaccine candidates, there are still no established correlates of protection. Previous experience in vaccine development for other pathogens shows that differences in vaccine formulation can result in diverse immune responses and consequently, different protective properties. Therefore the importance of continuing investigations on a broad range of strategies. Expertise in vaccine development in Brazil was refocused to the new coronavirus. Impressive collaboration between institutions will support further developments until we have available a safe, effective, and economically viable vaccine. Established competence and collaborations will allow preparedness for future challenges and can also be used to address local issues as neglected infectious diseases.

Plants as Sources of Anti-Inflammatory Agents.

Plants represent the main source of molecules for the development of new drugs, which intensifies the interest of transnational industries in searching for substances obtained from plant sources, especially since the vast majority of species have not yet been studied chemically or biologically, particularly concerning anti-inflammatory action. Anti-inflammatory drugs can interfere in the pathophysiological process of inflammation, to minimize tissue damage and provide greater comfort to the patient. Therefore, it is important to note that due to the existence of a large number of species available for research, the successful development of new naturally occurring anti-inflammatory drugs depends mainly on a multidisciplinary effort to find new molecules. Although many review articles have been published in this regard, the majority presented the subject from a limited regional perspective. Thus, the current article presents highlights from the published literature on plants as sources of anti-inflammatory agents.

Metabolic flux reprogramming in Mycobacterium tuberculosis-infected human macrophages.

Metabolic fluxes are at the heart of metabolism and growth in any living system. During tuberculosis (TB) infection, the pathogenic Mycobacterium tuberculosis (Mtb) adapts its nutritional behaviour and metabolic fluxes to survive in human macrophages and cause infection. The infected host cells also undergo metabolic changes. However, our knowledge of the infected host metabolism and identification of the reprogrammed metabolic flux nodes remains limited. In this study, we applied systems-based 13C-metabolic flux analysis (MFA) to measure intracellular carbon metabolic fluxes in Mtb-infected human THP-1 macrophages. We provide a flux map for infected macrophages that quantified significantly increased fluxes through glycolytic fluxes towards pyruvate synthesis and reduced pentose phosphate pathway fluxes when compared to uninfected macrophages. The tri carboxylic acid (TCA) cycle fluxes were relatively low, and amino acid fluxes were reprogrammed upon Mtb infection. The knowledge of host metabolic flux profiles derived from our work expands on how the host cell adapts its carbon metabolism in response to Mtb infection and highlights important nodes that may provide targets for developing new therapeutics to improve TB treatment.

CRISPR/Cas9 Approach to Generate an Auxotrophic BCG Strain for Unmarked Expression of LTAK63 Adjuvant: A Tuberculosis Vaccine Candidate.

Tuberculosis is one of the deadliest infectious diseases and a huge healthcare burden in many countries. New vaccines, including recombinant BCG-based candidates, are currently under evaluation in clinical trials. Our group previously showed that a recombinant BCG expressing LTAK63 (rBCG-LTAK63), a genetically detoxified subunit A of heat-labile toxin (LT) from Escherichia coli, induces improved protection against Mycobacterium tuberculosis (Mtb) in mouse models. This construct uses a traditional antibiotic resistance marker to enable heterologous expression. In order to avoid the use of these markers, not appropriate for human vaccines, we used CRISPR/Cas9 to generate unmarked mutations in the lysA gene, thus obtaining a lysine auxotrophic BCG strain. A mycobacterial vector carrying lysA and ltak63 gene was used to complement the auxotrophic BCG which co-expressed the LTAK63 antigen (rBCGΔ-LTAK63) at comparable levels to the original construct. The intranasal challenge with Mtb confirmed the superior protection induced by rBCGΔ-LTAK63 compared to wild-type BCG. Furthermore, mice immunized with rBCGΔ-LTAK63 showed improved lung function. In this work we showed the practical application of CRISPR/Cas9 in the tuberculosis vaccine development field.

Thirty years of recombinant BCG: new trends for a centenary vaccine.

Introduction: Global perception of the potential for Bacille Calmette-Guérin (BCG), and consequently recombinant BCG (rBCG), in a variety of prophylactic and therapeutic applications has been increasing. A century of information on BCG, and three decades of experience with rBCG, has generated solid knowledge in this field.Area covered: Here, we review the current state of knowledge of BCG and rBCG development. Molecular tools have facilitated the expression of a variety of molecules in BCG, with the aim of improving its efficacy as a tuberculosis vaccine, generating polyvalent vaccines against other pathogens, including viruses, bacteria, and parasites, and developing immunotherapy approaches against noninvasive bladder cancer. BCG's recently appraised heterologous effects and prospects for expanding its application to other diseases are also addressed.Expert opinion: There are high expectations for new tuberculosis vaccines currently undergoing advanced clinical trials, which could change the prospects of the field. Systems biology could reveal effective biomarkers of protection, which would greatly support vaccine development. The development of appropriate large-scale production processes would further support implementation of new vaccines and rBCG products. The next few years should consolidate the broader applications of BCG and produce insights into improvements using the recombinant BCG technology.

Bioanalytical method validation for the quantification of the chlorogenic acid in Capsicum baccatum through High Performance Liquid Chromatography (HPLC-DAD).

The fruit pulp extracts of the species Capsicum baccatum are associated with a number of phenolic compounds. The aim of this study was to validate a bioanalytical method for the quantification of the chlorogenic acid present in the UENF 1613 de C. baccatum accession. The quantification was carried out through HPLC. The results obtained for the extract of C. baccatum indicated selectivity for chlorogenic acid. The values obtained for relative standard deviation, as well as for precision, in terms of repeatability and intermediate precision, did not exceed the maximum of 15% set in the criteria for the acceptance of bioanalytical methods. In terms of recovery, the accuracy rate for the phenolic compound of interest was from 77 to 93%. The validated method through external standardization was applied for the quantification of chlorogenic acid of the UENF accession.

Um olhar sobre a saúde das mulheres cuidadoras de idosos: desafios e possibilidades / A look at the health of women caregivers of elderly people: challenges and opportunities / Una mirada a la salud de las mujeres cuidadoras de ancianos: desafíos y oportunidades

O objetivo deste estudo é avaliar como as mulheres cuidadoras realizam o seu autocuidado durante o período em que estão dispensando atenção ao idoso dependente. Trata-se de uma pesquisa descritiva, de abordagem qualitativa, desenvolvida com nove mulheres cuidadoras, formais ou informais, de idosos. O estudo permite afirmar a necessidade de serviços e programas sociais destinados às mulheres cuidadoras de idosos, apoiando-as no exercício desta função, visto que as evidências mostram necessidades de atenção e estímulo para o seu autocuidado.

The goal of this study is to evaluate how women caregivers realize their self-care during the period they are offering attention to the dependent elderly. This is a descriptive, qualitative approach, developed with nine women caregivers of elderly people, either formal or informal. The study can sustain the need for social services and programs for women caregivers of elderly people, supporting them in the occupation of caring for the elderly, as the evidence shows that they need attention and encouragement for their self-care.

El objetivo de este estudio es evaluar como las cuidadoras realizan su autocuidado durante el período en que están dedicando atención a las personas mayores dependientes. Se trata de un estudio descriptivo, cualitativo, desarrollado con nueve mujeres cuidadoras formales o informales de personas mayores. El estudio permite afirmar la necesidad de servicios y programas sociales para las mujeres cuidadoras de las personas mayores, apoyándolas en la actividad de cuidar de ancianos, visto que las evidencias muestran que estas necesitan atención y estímulo para el autocuidado.

Desenvolvimento e avaliação de filme antimicrobiano aromatizado para aplicação em massa de pastel / Development and evaluation of antimicrobial and flavored film for using on pastry dough

A indústria de alimentos, buscando atender à crescente demanda dos consumidores, vem desenvolvendo embalagens ativas para proporcionar qualidade e segurança aos produtos acondicionados. Este trabalho objetivou desenvolver e avaliar a aplicação de filmes ativos aromatizados em contato com a massa de pastel. Os filmes foram preparados pelo método casting, adicionados de ácido sórbico e aroma de pizza e avaliados in vitro frente ao microrganismo Penicillium sp. Também foram estudadas suas propriedades mecânicas, migração de ácido sórbico, avaliação sensorial do produto e análise microbiológica in vivo. Os filmes ativos apresentaram atividade antimicrobiana tanto in vitro como no alimento. A caracterização mecânica mostrou que os filmes ativos aromatizados apresentaram valores de carga máxima na ruptura, inferiores ao filme controle e, durante a migração, a adição de aroma contribuiu para uma maior liberação do ácido sórbico. Além disso, as massas de pastel em contato com os filmes ativos aromatizados apresentaram melhores resultados sensoriais.

The food industry, trying to meet growing consumer demand, is developing active packaging to provide quality and safety for packed food. This research aimed to develop and evaluate the implementation of active flavored films in contact with pastry dough. The active films were evaluated for in vitro antimicrobial activity against Penicillium sp. The mechanical properties of the films, the sorbic acid migration, sensory and in vivo microbiological analyses were also tested. The active films showed better results for in vitro and in vivo microbiological analyses when compared with the film with the sorbic acid incorporated directly on the pastry dough. The incorporation of sorbic acid and flavor affected the mechanical properties of the active films compared to the control film. The flavor addition provided a larger migration of sorbic acid from the film to the pastry dough. Besides the pastry dough packed in the active films showed better sensory results.