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Fungicides are often used prophylactically, to control fungal diseases. Although fungicides have been designed to control pests/fungi, they frequently share molecular targets with non-target species, including humans. Tebuconazole, a fungicide belonging to the class of triazoles, is widely employed, has moderate to high persistence in soil, and can be found in different environmental levels. This fungicide is metabolized to the main hydroxy-derived metabolite, Tebuconazole-tert-butyl-hydroxy (or hydroxytebuconazole). This study aims to unveil the action mechanism of Tebuconazole and the role played by its metabolite, Tebuconazole-tert-butyl-hydroxy (5-(4-Chlorophenyl)-2,2-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)-1,3-pentanediol), within the expected spectrum of toxicity. In silico and in vitro analyses (MTT assay, cell cycle evaluation, annexin/PI assay, ROS accumulation assay, and mitochondrial membrane potential determination) were performed in HepG2 cells for 24 h and 48 h. Although in silico analysis suggested that both Tebuconazole and Tebuconazole-tert-butyl-hydroxy are potentially hepatotoxic, only Tebuconazole affected the tested cell line. Reduced MTT metabolism, and decreased mitochondrial membrane potential were the main findings. In conclusion, the action mechanism of Tebuconazole may be related to mitochondrial dysfunction. However, the findings of this study pointed out that Tebuconazole-tert-butyl-hydroxy does not play an important role in Tebuconazol toxicity. The study has generated new data that will help to understand how fungicides behave in the environment.

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Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or dipyrido[3,2-a:2'3'-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 µM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 µM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).

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Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity.

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INTRODUCTION AND HYPOTHESIS: The high prevalence of pelvic floor disorders in women requires assessments using validated instruments. We aimed to translate, cross-culturally adapt to Brazilian Portuguese, and analyze the measurement properties of the International Consultation on Incontinence Questionnaire Vaginal Symptoms Module (ICIQ-VS-Br). METHODS: Participants were Brazilian women older than 18 years presenting vulvovaginal symptoms according to the Vulvovaginal Symptoms Questionnaire (VSQ-Br). The development of the ICIQ-VS-Br included the steps of translation, synthesis, back-translation, expert meeting, and pre-test. We analyzed construct validity by correlating the ICIQ-VS-Br and VSQ-Br. The participants answered the ICIQ-VS-Br the second time 7 to 10 days after the first response. We measured test-retest reliability using intraclass correlation coefficient (ICC), internal consistency using Cronbach's alpha, and construct validity using Pearson's correlation coefficient. RESULTS: The study included 313 women. Reproducibility was analyzed for the three subscales of the ICIQ-VS-Br, resulting in an ICC of 0.92 (95% CI 0.89 to 0.94) for "vaginal symptoms," 0.85 (95% CI 0.78 to 0.89) for "sexual matters," and 0.87 (95% CI 0.81 to 0.91) for "quality of life." Construct validity showed a moderate correlation between ICIQ-VS-Br and VSQ-Br, confirming our hypotheses. CONCLUSIONS: The ICIQ-VS-Br demonstrated validity and reproducibility, indicating that the instrument can be used in scientific research and clinical practice.

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A caça às bruxas foi o primeiro genocídio de proporções intercontinentais da era moderna e coincidiu com marcos históricos cruciais para a constituição da modernidade no Ocidente, como a Revolução Científica e a colonização das Américas. As mulheres condenadas como bruxas eram, em sua maioria, parteiras, benzedeiras e curandeiras não profissionais, que davam suporte às populações camponesas e às classes baixas. A perseguição e o extermínio destas mulheres representou também a marginalização de dimensões epistêmicas que propunham uma dimensão mágica, baseada em cosmologias originárias e numa concepção animista do mundo e, portanto, na convivência integrada entre os seres humanos e a natureza, constituindo também um epistemicídio. Isso aconteceu à medida que a Revolução Científica avançava e a medicina se institucionalizava, e se constituía como uma profissão nova, regulamentada e masculina. Esta pesquisa dedica-se a investigar as marcas deixadas por este fenômeno e sua importância na formação de um sistema de saber-poder, a fim de descobrir "se" e "como" seus efeitos se perpetuam na atualidade. Partimos da hipótese, defendida por diversos autores, de que o genocídio não se limitou à Europa, mas foi exportado para outros territórios com as invasões de terras ameríndias -- juntamente com os conceitos de gênero e raça --, ganhando novos contornos e retroalimentando a perseguição europeia. A interconexão entre os interesses e a atuação do Estado e da Igreja, nos permitiu detectar um projeto extenso e complexo de expansão e dominação política, econômica e cultural, que, em última instância, usava da religião como ferramenta de imposição ideológica e da violência, em suas diversas formas, como mecanismo de dominação social. De uma perspectiva foucaultiana, entendemos a caça às bruxas também como um fenômeno "fundado na" e "fundante da" diferença de gênero e do dimorfismo sexual, enquanto ficção biológica, e nos dedicamos a tentar mapear até que ponto ele pode ter contribuído para a instauração de outros marcadores da diferença a partir da biologia e da ciência, como é o caso da raça. Identificamos que o desencantamento do mundo e a biologização da alteridade, fundados no genocídio e no epistemicídio foram fundamentais à exploração humana e natural (divisão que não endossamos), que marcou de maneira crescente os últimos séculos, permitindo o desenvolvimento do capitalismo industrial e tecnológico, e inaugurando o processo que nos trouxe à emergência climática e humana sem precedentes com que hoje nos defrontamos.

The witch-hunting was the first genocide of intercontinental proportions in the modern era and coincided with crucial historical milestones for the constitution of modernity in the West, such as the Scientific Revolution and the colonization of the Americas. Most of the women condemned as witches were non-professional midwives, healers, and herbalists who supported peasant populations and the lower classes. The persecution and extermination of these women also represented the marginalization of epistemological dimensions that proposed a magical dimension, based on original cosmologies and an animistic conception of the world. Therefore, it was rooted in the integrated coexistence between human beings and nature, constituting an epistemicide. This occurred as the Scientific Revolution progressed, and medicine became institutionalized and established as a new, regulated, and male-dominated profession. This research is dedicated to investigating the impact left by this phenomenon and its importance in the formation of a knowledge-power system, aiming to discover if and how its effects continue to persist today. We begin with the hypothesis, defended by several authors, that the genocide was not limited to Europe but was exported to other territories through the invasions of Amerindian lands, along with the concepts of gender and race. This exportation resulted in new manifestations and fed back into the European persecution. The interconnection between the interests and actions of the State and the Church enabled us to identify an extensive and complex project of expansion and political, economic, and cultural domination. Ultimately, religion was used as a tool for ideological imposition and violence, in its various forms, as a mechanism of social domination. From a Foucauldian perspective, we understand the witch-hunting as a phenomenon that both relied on and established gender difference and sexual dimorphism as a biological fiction. We delve into mapping to what extent it may have contributed to the establishment of other markers of difference based on biology and science, such as race. We have identified that the disenchantment of the world and the biologization of otherness, rooted in genocide and epistemicide, were fundamental to the exploration of both human beings and nature. This division, which we do not endorse, has increasingly marked the past centuries, allowing the development of industrial and technological capitalism. This process has brought us to the unprecedented climate and human emergency we face today.

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This study aimed to evaluate the effect of Bifidobacterium animalis subsp. lactis (B. lactis) HN019 in drinking water on the development of apical periodontitis (AP) in rats. In total 60 animals were divided into a control group (sound teeth); Group I - regular water without AP; Group II - probiotic water without AP; Group III - regular water with AP; Group IV - probiotic water with AP. AP was induced after 3 days in the control groups and after 7, 21, and 42 days in groups III and IV. The animals were euthanized, and the mandibles were subjected to histotechnical processing. Samples were stained with hematoxylin & eosin (H&E) to identify root canal features, apical and periapical regions. Additionally, histoenzymology was performed to detect osteoclasts, immunohistochemistry was used to identify osteoclastogenesis markers, and the Brown & Brenn technique was applied for microbiological analysis. The data were analyzed using GraphPad Prism 8.0.1 with a significance level of 5%. Although no statistical differences were observed, the groups administered with probiotics showed better conditions in terms of histological aspects seen microscopically. Furthermore, there were no differences in the number of osteoclasts (p > 0.05). The RANKL marker was not found in the probiotic group at 42 days, unlike in group III.

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The aim of the present study was to evaluate, in vitro, the antimicrobial activity of the probiotic Bifidobacterium animalis subsp. lactis HN019, through the well technique, against 10 microorganisms can be found involved in endodontic infections. The antimicrobial activity of the probiotic was performed on Streptococcus mutans, Streptococcus sobrinus, Lacticaseibacillus casei, Enterococcus faecalis, Staphylococcus aureus, Candida albicans, Porphyromonas gingivalis, Porphyromonas endodontalis, Fusobacterium nucleatum and Prevotella intermedia. For the control group, it was used non-pathogenic bacteria Escherichia coli, Saccharomyces cerevisiae, and Kocuria rizhopilla. After 48 to 72 h of incubation of the petri dishes containing the culture medium, the microorganism strains, and the probiotic, the plates were examined to assess the uniformity of microbial growth, presence of contaminants, and the halo of inhibition. After visual inspection, the reading of the halo of inhibition was performed with the aid of a digital caliper using a reflected light source to illuminate the inverted plate on a black, opaque background after removing the cap. Thus, 3 values were obtained from each bacterial inoculum, which were added and divided by three to obtain the average of the values. The results of the in vitro study demonstrated that the probiotic B. animalis subsp. lactis HN019 promoted the inhibition of all strains of the pathogens evaluated, with the exception of Candida albicans, demonstrating antimicrobial activity on these microorganisms.

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INTRODUCTION AND HYPOTHESIS: The worldwide prevalence of sexual dysfunction in women is high; therefore, an adequate assessment of this condition is necessary, with instruments validated for the Brazilian population. The aim was to translate and adapt the International Consultation on Incontinence Questionnaire Female Sexual Matters Associated with Lower Urinary Tract Symptoms into Brazilian Portuguese (ICIQ-FLUTSsex-Br) and analyze its measurement properties. METHODS: We recruited Brazilian women, literate, over 18 years old, who had had sexual intercourse in the last 4 weeks and had urinary loss. The translation and cross-cultural adaptation were performed following five stages: translation, synthesis, back translation, expert committee review, and pre-test. Measurement properties were analyzed using SPSS software, as follows: test-retest reliability using the intraclass correlation coefficient (ICC); construct validity using Pearson's correlation coefficient, by correlating the ICIQ-FLUTSsex-Br with the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). RESULTS: A total of 328 women participated in the study. The reproducibility was 0.88, the standard error of measurement was 0.29, and the minimal detectable change was 0.80 (95% CI). Moderate correlations were found between the total scores of the ICIQ-FLUTSsex and PISQ-12 questionnaires (0.54, p<0.01), confirming the hypotheses outlined. Weak correlations were also found for comparisons between the FSFI and ICIQ-FLUTSsex total scores (-0.56, p<0.01) and the PISQ-12 question about fear of incontinence hindering sexual intercourse (0.26, p<0.01). CONCLUSION: The Portuguese-language version of the ICIQ-FLUTSsex-Br showed validity and reproducibility, making it a tool to be used in research and clinical practice by health professionals in Brazil.

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As doenças diarreicas agudas (DDA) são consideradas um grave problema de saúde pública mundial. No Brasil, elas afetam de forma desproporcional a população, majoritariamente as que se encontram expostas a condicionantes de determinação social que expressam sua vulnerabilidade. O objetivo deste estudo foi analisar a ocorrência de casos de DDA nos municípios da XII Região de Saúde do estado de Pernambuco e sua correlação com os indicadores de vulnerabilidade social de seus municípios. Trata-se de um estudo de natureza epidemiológica e de caráter analítico ecológico realizado na XII Região de Saúde do estado de Pernambuco, no período de 2016 a 2020. Os dados foram coletados no Sistema de Informação da Vigilância Epidemiológica de Doenças Diarreicas Agudas e no Atlas da Vulnerabilidade Social do Instituto de Pesquisa Econômica Aplicada. Foram utilizados o coeficiente de correlação de Pearson e a regressão linear simples. Verificou-se correlação negativa estatisticamente significante entre a ocorrência de casos de DDA e os índices de vulnerabilidade social de renda e trabalho (p = 0,029). Concluiu-se que a alta vulnerabilidade social de renda e trabalho da população comprova sua relação com as DDA, sendo necessária a criação de políticas públicas mais eficientes para sua prevenção e controle.

Acute diarrheal diseases (ADD) are considered a serious public health problem worldwide. In Brazil, they disproportionately affect the population, mostly those that are exposed to conditions of social determination that express their social vulnerability. The objective of this study was to analyze the occurrence of ADD cases in the municipalities of the XII Health Region of the state of Pernambuco and its correlation with the indexes of social vulnerability in their municipalities. This is an epidemiological study with an ecological analytical character carried out in the XII Health Region of the state of Pernambuco, from 2016 to 2020. Data were collected from the Information System of the Epidemiological Surveillance of Acute Diarrheal Diseases and the Atlas of Social Vulnerability of the Institute of Applied Economic Research. Pearson's correlation coefficient and simple linear regression were used. There was a statistically significant negative correlation between the occurrence of ADD cases and the indexes of social vulnerability of income and work (p = 0.029). In conclusion, the population's high social vulnerability in terms of income and work proved its relationship with ADD, making it necessary to create more efficient public policies for its prevention and control.

Las enfermedades diarreicas agudas (EDA) son un grave problema de salud pública a nivel mundial. En Brasil, afectan de manera desproporcionada a la población, en su mayoría las que están expuestas a condicionantes de determinación social que expresan su vulnerabilidad. El objetivo de este estudio es analizar la ocurrencia de casos de EDA en los municipios de la XII Región Sanitaria del estado de Pernambuco (Brasil) y su correlación con los indicadores de vulnerabilidad social en sus municipios. Se trata de un estudio epidemiológico con carácter analítico ecológico, realizado en la XII Región Sanitaria del estado de Pernambuco, en el período de 2016 a 2020. Los datos se recolectaron del Sistema de Información de Vigilancia Epidemiológica de Enfermedades Diarreicas Agudas y del Atlas de Vulnerabilidad Social del Instituto de Investigaciones Económicas Aplicadas. Se utilizaron el coeficiente de correlación de Pearson y la regresión lineal simple. Hubo una correlación negativa estadísticamente significativa entre la ocurrencia de casos de EDA y los indicadores de vulnerabilidad social ingreso y trabajo (p = 0,029). Se concluye que la alta vulnerabilidad social de ingresos y trabajo de la población demuestra su relación con las EDA, lo que hace necesario implementar políticas públicas más eficientes para su prevención y control.

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