Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection.

OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.

The centrality of workers to sustainability based on values: Exploring ergonomics to introduce new rationalities into decision-making processes.

This article presents the results of an academic research project connecting the discipline of ergonomics (and work-related issues) with the theme of sustainability. Despite the stated aim of creating value for stakeholders, including employees, companies face difficulties in introducing effective sustainability policies. The research question addressed in this article is the following: How can companies improve their decision-making processes to increase workers' wellbeing using policies integrating issues related to corporate sustainability and ergonomics? Currently, corporate sustainability is focused mainly on the triple bottom line (TBL) concept. In this context, the integration of ergonomics is fragmented and arguably separate from strategic human-resource functions (which have largely been the primary promoter of the internal-social component of corporate sustainability). This research argues that corporate sustainability requires a new step, improving the decision-making process, with the inclusion of more types of rationalities and the recognition of the centrality of workers in the process of creating sustainable action. When corporate sustainability policies focus on worker centrality, they open space for the integration of ergonomics as a pillar of an organization's corporate sustainability strategy. Based on a complex view of work systems, ergonomics can introduce values aligned with sustainability and promote cooperation in organizations. Different stakeholders working at companies can make use of different concepts proposed by ergonomics and other work sciences to support changes in their decision-making processes. In view of broader sustainability objectives, integrating different work-related considerations can help improve performance, including productivity, quality and health.

Knowledge Among University Students in Rio de Janeiro Regarding Transplant Organ Donation.

INTRODUCTION: Organ transplantation is often the only possible treatment to save the lives of patients with end-stage organ failure. Limiting factors include failure to notify in cases of patients with brain death, the inefficient procurement and distribution of organs, the lack of specific educational policies for health care professionals, lack of knowledge on the organ transplantation process, and family refusal for organ donation. OBJECTIVE: To evaluate the knowledge of students enrolled in different undergraduate university courses in Rio de Janeiro on the regulations and strategies governing transplant organ donation in Brazil. METHODS: This qualitative, observational study used a 10-item questionnaire aimed at obtaining data on respondents' general knowledge regarding organ donation and transplantation. The questionnaire was applied using either a printed or an electronic version developed on Google Forms and was completed anonymously. RESULTS: Overall, 587 questionnaires were completed. The participants were divided into 3 groups according to their field of study: 256 (43.6%) from courses related to arts and humanities, 159 (27.1%) from science and technology-related courses, and 172 (29.3%) from the biomedical field. Most respondents (396; 67.5%) were unaware of the criteria required to be an organ transplant donor. CONCLUSION: There is a significant lack of knowledge among university students on issues related to the organ donation and transplantation process in Brazil.

Bivariate and multivariate analyses of the correlations between stability of the erythrocyte membrane, serum lipids and hematological variables.

The observation that the fluidity must remain within a critical interval, outside which the stability and functionality of the cell tends to decrease, shows that stability, fluidity and function are related and that the measure of erythrocyte stability allows inferences about the fluidity or functionality of these cells. This study determined the biochemical and hematological variables that are directly or indirectly related to erythrocyte stability in a population of 71 volunteers. Data were evaluated by bivariate and multivariate analysis. The erythrocyte stability showed a greater association with hematological variables than the biochemical variables. The RDW stands out for its strong correlation with the stability of erythrocyte membrane, without being heavily influenced by other factors. Regarding the biochemical variables, the erythrocyte stability was more sensitive to LDL-C. Erythrocyte stability was significantly associated with RDW and LDL-C. Thus, the level of LDL-C is a consistent link between stability and functionality, suggesting that a measure of stability could be more one indirect parameter for assessing the risk of degenerative processes associated with high levels of LDL-C.

Fish hemoglobins.

Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta) and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemical strategies to adapt to the changing environmental gas availability. Structurally, most fish hemoglobins are tetrameric; however, those from some species such as lamprey and hagfish dissociate, being monomeric when oxygenated and oligomeric when deoxygenated. Fish blood frequently possesses several hemoglobins; the primary origin of this finding lies in the polymorphism that occurs in the globin loci, an aspect that may occasionally confer advantages to its carriers or even be a harmless evolutionary remnant. On the other hand, the functional properties exhibit different behaviors, ranging from a total absence of responses to allosteric regulation to drastic ones, such as the Root effect.

Coexpression of cytokeratin and vimentin in mice trophoblastic giant cells.

Trophoblastic giant cells reach their maximum size and exhibit a conspicuous synthetic and invasive activity during mouse placentation. The cytoskeleton, given the complex functions of the cells, shows a well-developed network of intermediate filament proteins. Immunohistochemistry combined with confocal and conventional immunofluorescence studies of intermediate filaments proteins cytokeratin and vimentin were performed in mice trophoblastic giant cells on days 9-11 of pregnancy. Specimens were fixed in phosphate-buffered formaldehyde and tissues were processed for routine paraffin embedding. Trophoblastic giant cells from antimesometrial, lateral or mesometrial uterine regions, through days 9-11 of pregnancy, expressed the same staining with both immunoperoxidase and immunofluorescent techniques. Cytokeratin filamentous structures were intensely immunoreactive and were detected throughout the cells cytoplasm; a few cells exhibited strongest fluorescence in the peripheral cytoplasm. Vimentin-positive staining was often distributed throughout the cells cytoplasm, most frequently and more intensely in the peripheral region; in some cells, it was present only in the peripheral regions. It is probable that expression of vimentin in midpregnancy trophoblastic giant cells may be associated with the rapid and conspicuous increase in size and synthetic activity of the cells and also with phagocytosis of degraded materials and invasion of decidual tissue.

Use of recombinant granulocyte-macrophage colony stimulating factor in the Brazil radiation accident.

8 patients with bone marrow failure after a caesium-137 radiation accident were treated with recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF). The 7 who were evaluable had prompt increases in granulocytes and bone marrow cellularity. 2 patients died of radiation toxicity and haemorrhage and 2 of bacterial sepsis acquired before the start of rHuGM-CSF treatment. 4 patients survive, including 2 who were treated early and never became infected. This therapeutic approach to radiation-induced granulocytopenia may therefore be useful after radiation and nuclear accidents.