Functional Foods from Black Rice (Oryza sativa L.): An Overview of the Influence of Drying, Storage, and Processing on Bioactive Molecules and Health-Promoting Effects.

Black rice (Oryza sativa) stands out for its high content of bioactive compounds with functional properties that play an important role in health benefits. The phytochemical level is affected by industrial processing due to its instability to the hydrothermal process. Studies about the influence of industrial processing on the phytochemical profile of black-rice-based foods are still scarce. This study carried out a comprehensive review of the influence of industrial applications on the bioactive compounds in food products based on black rice and their health-promoting effects. Most industrial processes such as drying, storage, cooking, and extrusion affect phytochemical content and antioxidant capacity. Alternatively, technologies such as fermentation, UV-C irradiation, and sprouting can maintain or improve the phytochemical content in black rice products.

Insight into inflammation involvement in varicocele: A narrative review.

BACKGROUND: Varicocele is one of the main causes of male infertility. Although the pathophysiology mechanism of varicocele is very well described and understood, there are some unanswered questions that remains unknown. Some studies have previously described the state of testicular inflammation and sperm in animal models, especially the mouse model, and the seminal plasma of men with varicocele, with or without changes in semen parameters. METHODS OF STUDY: This review intended to verify the role of inflammatory mechanism in varicocele, using clinical studies as well as animal model studies on the effect of inflammation caused by varicocele on the function of testicular somatic and germ cells. RESULTS: In-vivo studies confirmed whether anti-inflammatory molecules could treat the semen of men with varicocele and rats with varicocele. The use of different anti-inflammatory agents in mouse model studies provided a new perspective for future clinical studies to investigate the effect of concurrent treatment with surgery to improve surgical outcomes. CONCLUSION: Similar to animal model studies, previously conducted clinical trials have demonstrated the effectiveness of anti-inflammatory therapy in varicocele patients. However, clinical trials using anti-inflammatory are needed to be conducted agents to evaluate different aspects of this therapeutical approach in varicocele patients.

Risk and prevalence of oral cancer in patients with different types of lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to assess the risk and prevalence of oral cancer in patients with systemic lupus erythematosus (SLE) or discoid lupus erythematosus (DLE). STUDY DESIGN: The review included observational cohort and cross-sectional studies that investigated the incidence or prevalence of oral cancer in adults with confirmed diagnoses of SLE or DLE. Studies were selected based on predefined eligibility criteria, including the use of specific diagnostic criteria for SLE and DLE. After searches in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, LILACS, and LIVIVO databases and gray literature for relevant studies, the selection process was conducted by independent reviewers. RESULTS: A total of 5,545 articles were identified. After screening, 8 studies met the inclusion criteria. The pooled risk estimate indicated a significantly increased risk of oral cancer in patients with SLE (risk ratio = 2.69; 95% confidence interval, 1.75 to 4.16; I2 = 0%; P = .78) compared with the general population. The pooled prevalence of oral cancer in patients with DLE was 10% (95% ci, 0.03 to 0.13; I2 = 59%; P = .12). CONCLUSIONS: This review provides evidence supporting an elevated risk for individuals with SLE or DLE developing oral cancer. The findings highlight the importance of monitoring oral mucosa in patients with these conditions.

Pregnancy and postpartum experiences of women undergoing hemodialysis: a qualitative study / Experiências de gravidez e puerpério de mulheres em hemodiálise: um estudo qualitativo

ABSTRACT Introduction: There are particularities of chronic kidney disease (CKD) in women and their treatment. The biology of women exposes them to greater risk factors for CKD and both pregnancy and the postpartum period place an additional burden on renal health. Pregnancy complications may cause or worsen CKD. Objective: To explore the experiences of women with CKD undergoing hemodialysis in relation to their reproductive history. Methods: This study consisted of clinical-qualitative design with semi-structured individual interviews and open-ended questions. The sample selection was intentional and according to the theoretical saturation criterion. The data analysis was carried out based on the seven steps of the clinical-qualitative content analysis and validated by Nvivo11. This study was conducted in a public hemodialysis clinic of the Brazilian National Health System. Results: Twelve women undergoing hemodialysis were interviewed. The results from the analysis revealed three categories: 1) Association of pregnancy with CKD; 2) Nebulosity in relation to diagnosis and reproductive history 3) Being a woman undergoing hemodialysis. Conclusion: Our study showed the importance of considering the specificities of CKD in women, suggesting that these issues are important for diagnosis and treatment adherence. Consideration of reproductive life history allows the health of women undergoing hemodialysis to be promoted holistically, including aspects of mental health.

Resumo Introdução: Existem particularidades da doença renal crônica (DRC) em mulheres e seu tratamento. A biologia das mulheres as expõe a fatores de risco mais elevados para DRC e tanto a gravidez quanto o puerpério implicam um ônus adicional à saúde renal. Complicações na gestação podem causar ou piorar a DRC. Objetivo: Explorar as experiências de mulheres com DRC submetidas à hemodiálise em relação ao seu histórico reprodutivo. Métodos: Este estudo consistiu em desenho clínico-qualitativo com entrevistas individuais semiestruturadas e questões abertas. A seleção da amostra foi intencional e de acordo com o critério de saturação teórica. A análise de dados foi realizada com base nos sete passos da análise clínico-qualitativa de conteúdo e validada pelo Nvivo11. Este estudo foi realizado em uma clínica pública de hemodiálise do Sistema Único de Saúde brasileiro. Resultados: Foram entrevistadas 12 mulheres em hemodiálise. Os resultados da análise revelaram três categorias: 1) Associação da gravidez com DRC; 2) Nebulosidade em relação ao diagnóstico e à história reprodutiva; 3) Ser mulher e fazer hemodiálise. Conclusões: Nosso estudo mostrou a importância de considerar as especificidades da DRC em mulheres, sugerindo que estas questões são importantes para o diagnóstico e a adesão ao tratamento. A consideração do histórico de vida reprodutiva permite promover de forma holística a saúde das mulheres submetidas à hemodiálise, incluindo aspectos de saúde mental.

Role of Cystathionine ß-Synthase and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics of Murine Breast Cancer Cells.

Cystathionine ß-synthase (CBS), CSE (cystathionine γ-lyase) and 3-mercaptopyruvate sulfurtransferase (3-MST) have emerged as three significant sources of hydrogen sulfide (H2S) in various forms of mammalian cancer. Here, we investigated the functional role of CBS' and 3-MST's catalytic activity in the murine breast cancer cell line EO771. The CBS/CSE inhibitor aminooxyacetic acid (AOAA) and the 3-MST inhibitor 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) were used to assess the role of endogenous H2S in the modulation of breast cancer cell proliferation, migration, bioenergetics and viability in vitro. Methods included measurements of cell viability (MTT and LDH assays), cell proliferation and in vitro wound healing (IncuCyte) and cellular bioenergetics (Seahorse extracellular flux analysis). CBS and 3-MST, as well as expression were detected by Western blotting; H2S production was measured by the fluorescent dye AzMC. The results show that EO771 cells express CBS, CSE and 3-MST protein, as well as several enzymes involved in H2S degradation (SQR, TST, and ETHE1). Pharmacological inhibition of CBS or 3-MST inhibited H2S production, suppressed cellular bioenergetics and attenuated cell proliferation. Cell migration was only inhibited by the 3-MST inhibitor, but not the CBS/CSE inhibitor. Inhibition of CBS/CSE of 3-MST did not significantly affect basal cell viability; inhibition of 3-MST (but not of CBS/CSE) slightly enhanced the cytotoxic effects of oxidative stress (hydrogen peroxide challenge). From these findings, we conclude that endogenous H2S, generated by 3-MST and to a lower degree by CBS/CSE, significantly contributes to the maintenance of bioenergetics, proliferation and migration in murine breast cancer cells and may also exert a minor role as a cytoprotectant.

Genomic evidences of gulls as reservoirs of critical priority CTX-M-producing Escherichia coli in Corcovado Gulf, Patagonia.

Extended spectrum ß-lactamase (ESBL)-producing Enterobacterales has spread rapidly around the world, reaching remote areas. In this regard, wild birds that acquire ESBL producers from anthropogenically impacted areas can become reservoirs, contributing to further dissemination of antimicrobial-resistant bacteria categorized as critical priority pathogens to remote environments, during migration seasons. We have conducted a microbiological and genomic investigation on the occurrence and features of ESBL-producing Enterobacterales in wild birds from the remote Acuy Island, in the Gulf of Corcovado, at Chilean Patagonia. Strikingly, five ESBL-producing Escherichia coli were isolated from migratory and resident gulls. Whole-genome sequencing (WGS) analysis revealed the presence of two E. coli clones belonging to international sequence types (STs) ST295 and ST388, producing CTX-M-55 and CTX-M-1 ESBLs, respectively. Moreover, E. coli carried a wide resistome and virulome associated with human and animal infections. Phylogenomic analysis of global and publicly genomes of E. coli ST388 (n = 51) and ST295 (n = 85) clustered gulls isolates along to E. coli strains isolated from the environment, companion animal and livestock in the United States of America, within or close to the migratory route of Franklin's gull, suggesting a possible trans hemispheric movement of international clones of WHO critical priority ESBL producing pathogens.

Impact of pretreatments with ethanol and freezing on drying slice papaya: drying performance and kinetic of ultrasound-assisted extraction of phenolics compounds.

BACKGROUND: Pretreatments of drying can represent an alternative to minimize the negative aspect process on the dry samples. Thus, the influence of ethanol (ET) and freezing (FG) as drying pretreatments was analyzed for slices of papaya. The slices (5 mm) were submitted for drying kinetics (60 °C and 1.5 m s-1 ). Drying kinetics experimental data were fitted using Page's model and a diffusive model with boundary condition of types I and III. Also the thermophysical properties (thermal conductivity and specific heat) were determined and finally, the kinetics of ultrasound-assisted (40 kHz and 132 W) extraction of total phenolic compounds (TPCs) were realized. RESULTS: The combined method (ET + FG) was more efficient in reducing the drying time of papaya slices (48%) and the model 2 simulating the boundary condition of the third type (type III) showed the best fit to the experimental data. Effective diffusivity and convective coefficient were higher for ET + FG, where the maximum reduction in water content was 91% compared to fresh slices. The pretreatments did not influence the thermal conductivity, however, they were significant in the specific heat and in the extraction of TPCs, being higher in the time of 180 min. CONCLUSION: It was confirmed in the results presented that the combined pretreatment ET + FG is the most viable for drying papaya slices. Furthermore, it was found to be the most efficient in minimizing the loss of TPCs. Therefore, this pretreatment has great potential for application in the development of high value-added foods. © 2022 Society of Chemical Industry.

Characteristics of biscuits containing different proportions of whole mung bean, wheat and rice brown flours.

A simplex-centroid design was used to evaluate the effect of proportions (0 to 100%) of whole wheat flour (WWF), whole mung bean flour (WMF) and whole rice flour (BRF) on the quality of cookies savory. The dough cut in the shape of a disks (37 mm × 2 mm) showed a 13% retraction in diameter when they contained exclusively WWF, it was less intense (5%) with BRF and null (0%) with WMF. The dough expansion occurred only vertically, the thicknesses of the WWF, WMF and BRF biscuits were 5.33, 2.79 and 2.13 times greater than the initial dough height, respectively. This characteristic showed high correlations with volumetric expansion (r = 0.95), specific volume (r = 0.90), hardness (r = 0.92), fracturability (r = 0.93) and spread factor (r = -0.96). BRF increased the value of the color difference of the biscuits up to 17.70, the effect of WMF was smaller (6.51). Only the radial expansion index correlated with the trough (r = 0.76), final viscosity (r = 0.79) and setback (r = 0.77) parameters. Considering the main desirable physical characteristics in savory biscuits, the highest global desirability obtained was for the proportion of 49% WWF, 24% WMF and 27% BRF.

Pregnancy and postpartum experiences of women undergoing hemodialysis: a qualitative study.

INTRODUCTION: There are particularities of chronic kidney disease (CKD) in women and their treatment. The biology of women exposes them to greater risk factors for CKD and both pregnancy and the postpartum period place an additional burden on renal health. Pregnancy complications may cause or worsen CKD. OBJECTIVE: To explore the experiences of women with CKD undergoing hemodialysis in relation to their reproductive history. METHODS: This study consisted of clinical-qualitative design with semi-structured individual interviews and open-ended questions. The sample selection was intentional and according to the theoretical saturation criterion. The data analysis was carried out based on the seven steps of the clinical-qualitative content analysis and validated by Nvivo11. This study was conducted in a public hemodialysis clinic of the Brazilian National Health System. RESULTS: Twelve women undergoing hemodialysis were interviewed. The results from the analysis revealed three categories: 1) Association of pregnancy with CKD; 2) Nebulosity in relation to diagnosis and reproductive history 3) Being a woman undergoing hemodialysis. CONCLUSION: Our study showed the importance of considering the specificities of CKD in women, suggesting that these issues are important for diagnosis and treatment adherence. Consideration of reproductive life history allows the health of women undergoing hemodialysis to be promoted holistically, including aspects of mental health.

Efficacy of Clinically Used PARP Inhibitors in a Murine Model of Acute Lung Injury.

Poly(ADP-ribose) polymerase 1 (PARP1), as a potential target for the experimental therapy of acute lung injury (ALI), was identified over 20 years ago. However, clinical translation of this concept was not possible due to the lack of clinically useful PARP inhibitors. With the clinical introduction of several novel, ultrapotent PARP inhibitors, the concept of PARP inhibitor repurposing has re-emerged. Here, we evaluated the effect of 5 clinical-stage PARP inhibitors in oxidatively stressed cultured human epithelial cells and monocytes in vitro and demonstrated that all inhibitors (1-30 µM) provide a comparable degree of cytoprotection. Subsequent in vivo studies using a murine model of ALI compared the efficacy of olaparib and rucaparib. Both inhibitors (1-10 mg/kg) provided beneficial effects against lung extravasation and pro-inflammatory mediator production-both in pre- and post-treatment paradigms. The underlying mechanisms include protection against cell dysfunction/necrosis, inhibition of NF-kB and caspase 3 activation, suppression of the NLRP3 inflammasome, and the modulation of pro-inflammatory mediators. Importantly, the efficacy of PARP inhibitors was demonstrated without any potentiation of DNA damage, at least as assessed by the TUNEL method. These results support the concept that clinically approved PARP inhibitors may be repurposable for the experimental therapy of ALI.

Dentists' attitudes and practices toward evidence-based dentistry: a systematic review.

INTRODUCTION AND AIMS: Considering that attitudes toward evidence-based dentistry (EBD) may predict implementation behaviors, the objective of this systematic review was to synthesize and evaluate the existing evidence related to dentists' attitudes and practices toward EBD. METHODS: We included primary studies that collected information from interviews, questionnaires, or conversation sessions with dentists. The following sources were searched: Cochrane Central Register of Controlled Trials, Embase, PubMed, Scopus, and Web of Science, in addition to gray literature. The included studies were appraised according to the assessment tools recommended by the Joanna Briggs Institute for qualitative and quantitative observational studies. Descriptive data were collected in standardized tables and descriptively synthesized. RESULTS: The selection process resulted in 36 included studies. Dentists share positive opinions about EBD and predominantly report willingness to learn or adopt these practices. Despite high methodological risks and significant heterogeneity, the results collected in this review indicated that scientific journals, clinical practice guidelines, and trusted colleagues are generally perceived as influential and useful by dentists, who highly consulted these information sources. CONCLUSION: Despite supportive reported attitudes toward EBD, very low certainty exists about actual EBD-related practices.

"Tratamento precoce", antivacinação e negacionismo: quem são os Médicos pela Vida no contexto da pandemia de COVID-19 no Brasil? / "Early Treatment", Anti-Vaccination, and Denialism: who are the Doctors for Life in the COVID-19 pandemic context in Brazil?

Resumo O artigo pretende identificar quem são os "Médicos pela Vida" (MPV), suas informações acadêmicas e profissionais, quais as premissas utilizadas para a defesa do "tratamento precoce" e da negação das vacinas contra COVID-19 e qual a representatividade de seus discursos no contexto da prática médica no Brasil. A análise baseia-se na lista de 276 profissionais médicos catalogados no site dos MPV e em informações acadêmicas e profissionais coletadas nos sites do Conselho Federal de Medicina e da Plataforma Lattes, do Conselho Nacional de Desenvolvimento Científico e Tecnológico. A análise do conteúdo aponta para a centralidade das especialidades da Homeopatia e Acupuntura na população de MPV quando comparada ao conjunto dos especialistas do Brasil. A adesão significativa de homeopatas e acupunturistas ao movimento dos MPV pode iluminar a compreensão sobre racionalidades médicas específicas, permitindo distinguir quais categorias e ideias acerca dos processos de saúde e doença estão em disputa. Conclui-se que, para além de descrever a problemática, é preciso estabelecer suas correlações com um conjunto de acontecimentos, práticas, decisões políticas, encadeamentos econômicos, compartilhamento de crenças e uma corrente de processos que configuram seu caráter inegavelmente social.

Abstract The article aims to identify who the "Doctors for Life" are, their academic and professional information, which assumptions have been mobilized for the defense of "early treatment" and the denial of vaccines for COVID-19, and the representativeness of their discourses in the medical practice context in Brazil. The analysis is based on a list of 276 doctors' names, cataloged from their website, and on academic and professional information obtained through research on the Federal Medical Conseil website and the Scientific and Technological Development Nacional Council platform. The content analysis points to the centrality of the medical specialties of homeopathy and acupuncture in the population of Doctors for Life when compared to the set of specialist doctors in Brazil. The significant accession of homeopaths and acupuncturists to the Doctors for Life movement can clarify the understanding of specific medical rationalities, allowing us to distinguish which categories and ideas about the health-disease process are in dispute. It is concluded that, more than describing the problem, it is needed to establish its correlations with a group of events, practices, political decisions, economic linkages, shared beliefs, and a chain of processes that configure its undeniably social characteristics.

"Early Treatment", Anti-Vaccination, and Denialism: who are the Doctors for Life in the COVID-19 pandemic context in Brazil? / "Tratamento precoce", antivacinação e negacionismo: quem são os Médicos pela Vida no contexto da pandemia de COVID-19 no Brasil?

The article aims to identify who the "Doctors for Life" are, their academic and professional information, which assumptions have been mobilized for the defense of "early treatment" and the denial of vaccines for COVID-19, and the representativeness of their discourses in the medical practice context in Brazil. The analysis is based on a list of 276 doctors' names, cataloged from their website, and on academic and professional information obtained through research on the Federal Medical Conseil website and the Scientific and Technological Development Nacional Council platform. The content analysis points to the centrality of the medical specialties of homeopathy and acupuncture in the population of Doctors for Life when compared to the set of specialist doctors in Brazil. The significant accession of homeopaths and acupuncturists to the Doctors for Life movement can clarify the understanding of specific medical rationalities, allowing us to distinguish which categories and ideas about the health-disease process are in dispute. It is concluded that, more than describing the problem, it is needed to establish its correlations with a group of events, practices, political decisions, economic linkages, shared beliefs, and a chain of processes that configure its undeniably social characteristics.

O artigo pretende identificar quem são os "Médicos pela Vida" (MPV), suas informações acadêmicas e profissionais, quais as premissas utilizadas para a defesa do "tratamento precoce" e da negação das vacinas contra COVID-19 e qual a representatividade de seus discursos no contexto da prática médica no Brasil. A análise baseia-se na lista de 276 profissionais médicos catalogados no site dos MPV e em informações acadêmicas e profissionais coletadas nos sites do Conselho Federal de Medicina e da Plataforma Lattes, do Conselho Nacional de Desenvolvimento Científico e Tecnológico. A análise do conteúdo aponta para a centralidade das especialidades da Homeopatia e Acupuntura na população de MPV quando comparada ao conjunto dos especialistas do Brasil. A adesão significativa de homeopatas e acupunturistas ao movimento dos MPV pode iluminar a compreensão sobre racionalidades médicas específicas, permitindo distinguir quais categorias e ideias acerca dos processos de saúde e doença estão em disputa. Conclui-se que, para além de descrever a problemática, é preciso estabelecer suas correlações com um conjunto de acontecimentos, práticas, decisões políticas, encadeamentos econômicos, compartilhamento de crenças e uma corrente de processos que configuram seu caráter inegavelmente social.

Early physicians' mortality in Espírito Santo: a decade trend.

Introduction: Mortality data make it possible to develop indicators to guide the planning of health promotion and prevention actions in order to reduce mortality from preventable causes. However, there are no publications on physicians' mortality in the state of Espírito Santo, Brazil. Objectives: To describe mortality distribution and potential years of life lost from 2006 to 2015 among physicians who lived in Espírito Santo. Methods: This is a descriptive study of secondary data from the Mortality Information System of the Brazilian Ministry of Health. The distribution of socio-demographic variables and of basic cause of death was studied by absolute and relative frequencies. Potential years of life lost in each death were considered the years remaining from age at death up to the age limit of 70 years. Results: There were 20 deaths of female physicians (14.5%) and 118 (85.5%) of male physicians, with predominance of whites (87.9%) and married (56%) individuals. The main causes of death were neoplasms (39.1%), diseases of the circulatory system (19.6%), and external causes (19.6%). The majority of female and male deaths occurred from 60 to 69 years, but average death was significantly lower among women compared to men (respectively 58.3 and 67.0 years). Potential years of life lost totaled 1,226 years, with a mean of 14.6, which was greater in women (20.4) compared to men (13.4). Conclusions: Mortality trends observed in the general population were also present among physicians in Espírito Santo. However, contrary to the general population pattern, average death age was lower in women. Early mortality caused many lost years of life, especially among women.

Detecting KPC-2 and NDM-1 Coexpression in Klebsiella pneumoniae Complex from Human and Animal Hosts in South America.

Reports of Gram-negative bacteria harboring multiple carbapenemase genes have increased in South America, leading to an urgent need for appropriate microbiological diagnosis. We evaluated phenotypic methods for detecting Klebsiella pneumoniae carbapenemase 2 (KPC-2) and New Delhi metallo-ß-lactamase-1 (NDM-1) coexpression in members of the K. pneumoniae complex (i.e., K. pneumoniae, K. quasipneumoniae, and K. variicola) isolated from human and animal hosts, based on inhibition of ceftazidime-avibactam (CZA) and aztreonam (ATM) by dipicolinic acid (DPA), EDTA, or avibactam (AVI). While the presence of blaKPC-2 and blaNDM-1 genes was confirmed by whole-genome sequencing, PCR, and/or GeneXpert, coexpression was successfully detected based on the following: (i) a ≥5-mm increase in the zone diameter of ATM (30 µg) disks plus AVI (4 or 20 µg) and ≥4-mm and ≥10-mm increases in the zone diameters for "CZA 50" (30 µg ceftazidime [CAZ] and 20 µg AVI) and "CZA 14" (10 µg CAZ and 4 µg AVI) disks, respectively, when we added DPA (1 mg/disk) or EDTA (5 mM) in a combined disk test (CDT); (ii) a positive ghost zone (synergism) between ATM (30 µg) and CZA 50 disks and between CZA 50 and DPA (1 mg) disks, using the double-disk synergy test (DDST) at a disk-disk distance of 2.5 cm; (iii) ≥3-fold MIC reductions of ATM and CZA in the presence of AVI (4 µg/mL), DPA (500 µg/mL), or EDTA (320 µg/mL); and (iv) immunochromatography. Although our results demonstrated that inhibition by AVI, DPA, and EDTA may provide simple and inexpensive methods for the presumptive detection of coexpression of KPC-2 and NDM-1 in members of the K. pneumoniae complex, additional studies are necessary to confirm the accuracy of these methodologies by testing other Gram-negative bacterial species and other KPC and NDM variants coexpressed by WHO critical priority pathogens detected worldwide. IMPORTANCE Alerts regarding the emergence and increase of combinations of carbapenemases in Enterobacterales in Latin America and the Caribbean have recently been issued by PAHO and WHO, emphasizing the importance of appropriate microbiological diagnosis and the effective and articulated implementation of infection prevention and control programs. In this study, we evaluated methods based on inhibition of ceftazidime (CAZ), ceftazidime-avibactam (CZA), and aztreonam (ATM) by dipicolinic acid (DPA), EDTA, and avibactam (AVI) inhibitors for the identification of KPC-2- and NDM-1-coexpression in members of the K. pneumoniae complex recovered from human and animal hosts. Our results demonstrate that inhibition by AVI, DPA, and EDTA may provide simple and inexpensive methods for the presumptive detection of coexpression of KPC-2 and NDM-1 in members of the K. pneumoniae complex.

Effects of the PARP Inhibitor Olaparib on the Response of Human Peripheral Blood Leukocytes to Bacterial Challenge or Oxidative Stress.

Prior studies demonstrate the activation of poly-(ADP-ribose) polymerase 1 (PARP1) in various pathophysiological conditions, including sepsis. We have assessed the effect of olaparib, a clinically used PARP1 inhibitor, on the responses of human peripheral blood leukocytes (PBMCs) obtained from healthy volunteers in response to challenging with live bacteria, bacterial lipopolysaccharide (LPS), or oxidative stress (hydrogen peroxide, H2O2). The viability of PBMCs exposed to olaparib or to the earlier generation PARP inhibitor PJ-34 (0.1-1000 µM) was monitored using Annexin V and 7-aminoactinomycin D. To evaluate the effects of olaparib on the expression of PARP1 and its effects on protein PARylation, PBMCs were stimulated with Staphylococcus aureus with or without olaparib (1-10 µM). Changes in cellular levels of nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP), as well as changes in mitochondrial membrane potential (MMP), were measured in PBMCs exposed to H2O2. Bacterial killing was evaluated in PBMCs and polymorphonuclear leukocytes (PMNs) incubated with S. aureus. Cytokine production was measured in supernatants using a cytometric bead array. Reactive oxygen species (ROS), nitric oxide (NO) production, and phagocytic activity of monocytes and neutrophils were measured in whole blood. For ROS and NO production, samples were incubated with heat-killed S. aureus; phagocytic activity was assessed using killed Escherichia coli conjugated to FITC. Olaparib (0.1-100 µM) did not adversely affect lymphocyte viability. Olaparib also did not interfere with PARP1 expression but inhibits S. aureus-induced protein PARylation. In cells challenged with H2O2, olaparib prevented NAD+ and ATP depletion and attenuated mitochondrial membrane depolarization. LPS-induced production of TNF-α, MIP-1α, and IL-10 by PBMCs was also reduced by olaparib. Monocytes and neutrophils displayed significant increases in the production of ROS and NO after stimulation with S. aureus and phagocytic (E. coli) and microbicidal activity, and these responses were not suppressed by olaparib. We conclude that, at clinically relevant concentrations, olaparib exerts cytoprotective effects and modulates inflammatory cytokine production without exerting adverse effects on the cells' ability to phagocytose or eradicate pathogens. The current data support the concept of repurposing olaparib as a potential experimental therapy for septic shock.

Quality of Life of Pregnant Women with Systemic Lupus Erythematosus / Qualidade de vida de mulheres grávidas com lúpus eritematoso sistêmico

Abstract Objective To assess the quality of life (QoL) of pregnant women with systemic lupus erythematosus (SLE) treated at a high-risk prenatal outpatient clinic during the third trimester of gestation. Methods An observational descriptive study was performed in a high-risk prenatal outpatient clinic. Women in the third trimester of pregnancy and undergoing antenatal care between July 2017 and July 2019 answered the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire, consisting of 26 questions divided into 4 domains (physical, psychological, social and environmental). Results We interviewed 50 pregnant women with a mean gestational age of 30 weeks (standard deviation [SD]: 10 weeks) who were diagnosed with SLE. The average age of the participants was 30 years (SD: 14.85), and the average time since the diagnosis of SLE was of 9.06 years (SD: 6.8 years). Most participants had a partner, did not plan their pregnancy (76%), and did not use contraception prior to pregnancy (80%). The score of each domain ranges from 0 (the worst score) to 100 (the best score). The means ± SDs of the scores of the participants on each domain were: physical - 52.21 ± 18.44); psychological - 64.17 ± 18.56); social - 66.33 ± 27.09); and environmental - 64.56 (18.53). The means ± SDs of the general QoL, and health-related QoL items were of 70.50 ± 24.06 and 70.00 ± 30.72 respectively. Conclusion The physical domain presented the lowest scores compared with the other three domains. Pregnant women with SLE had high overall QoL scores, and their health-related QoL scores were also relatively high.

Resumo Objetivo Investigar a qualidade de vida (QV) de gestantes com lúpus eritematoso sistêmico (LES), em acompanhamento ambulatorial pré-natal de alto risco, durante o terceiro trimestre de gestação. Métodos Foi realizado um estudo observacional descritivo em ambulatório de prénatal de alto risco. Asmulheres emacompanhamento pré-natal no terceiro trimestre de gravidez entre julho de 2017 e julho de 2019 responderam ao questionário abreviado de Qualidade de Vida da Organização Mundial de Saúde (abbreviated World Health Organization Quality of Life, WHOQOL-BREF, em inglês), composto por 26 questões divididas em 4 domínios (físico, psicológico, social e ambiental). Resultados Foram entrevistadas 50 gestantes com diagnóstico de LES e média de 30 semanas de idade gestacional (desvio padrão [DP]: 10 semanas). A idade média das participantes foi de 30 anos (DP: 14,85), e o tempomédio desde o diagnóstico de lúpus foi de 9,06 anos (DP=15,55 anos). Amaioria das participantes tinha companheiro, não havia planejado a gravidez (76%), e não fazia uso de anticoncepcional antes da gravidez (80%). A pontuação em cada domínios varia de 0 (pior pontuação) a 100 (melhor pontuação). As médias± DPs das pontuações das participantes em cada domínios foram: físico - 52,21± 18,44; psicológico - 64,17± 18,56; social - 66,33± 27,09; e ambiental -64,56± 18,53). As médias± DPs dos itens relativos à QV geral e à QV relacionada à saude foram de 70,50± 24,06) e 70,00± 30,72, respectivamente. Conclusão O domínio físico apresentou as menores pontuações em comparação com os outros três domínios. Mulheres grávidas com LES tiveram pontuação alta no item de QV geral, e a pontuação no item de QV relacionada à saúde também foi relativamente alta.

Análise de impacto orçamentário dos inibidores de PARP no tratamento de manutenção em primeira linha de pacientes com câncer de ovário avançado, gBRCA mutado, sob a perspectiva do sistema de saúde suplementar brasileiro / Budget impact analysis of PARP inhibitors in the first line maintenance treatment of patients with advanced, gBRCA mutated, ovarian cancer, from the perspective of the Brazilian supplementary health system

Objetivo: O presente artigo visa disponibilizar aos gestores da saúde dados sobre o impacto orçamentário da incorporação dos inibidores de PARP (iPARPs) para o tratamento de primeira linha de manutenção de câncer de ovário avançado, gBRCA mutado, sob a perspectiva do sistema de saúde suplementar. Métodos: Adotou-se o método epidemiológico, tendo como comparador a vigilância ativa em um horizonte temporal de cinco anos. Foram considerados apenas os custos de tratamento medicamentoso na análise, utilizando o pressuposto conservador de que os custos da vigilância ativa são nulos. Além disso, construiu-se uma análise de sensibilidade determinística. Resultados: O impacto orçamentário dos iPARPs na população-alvo em todo o sistema foi de R$ 78,1 milhões em cinco anos acumulados. A análise de sensibilidade apontou que o resultado doimpacto orçamentário varia de R$ 54,6 milhões a R$ 101,6 milhões. A taxa de difusão da tecnologia e os parâmetros epidemiológicos foram os que exerceram a maior influência na variabilidade dos resultados. Conclusão: Os dados sugerem que a incorporação dos iPARPs na população selecionada gera um impacto orçamentário gerenciável.

Objective: The objective was to calculate the budget impact of PARP inhibitors (iPARPs) incorporation for the first-line maintenance treatment of advanced mutated gBRCA ovarian cancer from the perspective of the supplementary health system. Methods: We adopted the epidemiological method, with active surveillance as the comparator in a time horizon of five years. We considered only drug treatment's cost, using a conservative approach in which the costs with active surveillance are null. In addition, we developed a deterministic sensitivity analysis. Results: The budget impact of iPARPs on the target population was R$ 78.1 million in five years. The sensitivity analysis showed that the result of the budget impact ranges from R$ 54.6 million to R$ 101.6 million. The market share evolution and the epidemiological parameters had the highest impact on the result's variability. Conclusion: These data suggest that the incorporation of iPARPs in the selected population generates a manageable budget impact

Phylogeographical Landscape of Citrobacter portucalensis Carrying Clinically Relevant Resistomes.

During a surveillance study conducted to assess the occurrence and genomic landscape of critical priority pathogens circulating at the human-animal-environment interface in Brazil, as part of the Grand Challenges Explorations-New Approaches to Characterize the Global Burden of Antimicrobial Resistance program, two multidrug-resistant (MDR) Citrobacter portucalensis carrying blaCTX-M-15 extended-spectrum ß-lactamase (ESBL) genes, isolated from green sea turtles, were characterized. Genomic and phylogeographical analysis of C. portucalensis genomes available in public databases revealed the intercontinental dissemination of clades carrying different arrays of clinically relevant genes conferring resistance to carbapenems, broad-spectrum cephalosporins, cephamycins, aminoglycosides and fluoroquinolones, disinfectants, and heavy metals. Our observations suggest that C. portucalensis could be emerging as critical priority bacteria of both public and One Health importance worldwide. IMPORTANCE The global spread of antibiotic-resistant priority pathogens beyond the hospital setting is a critical issue within a One Health context that integrates the human-animal-environment interfaces. On the other hand, next-generation sequencing technologies along with user-friendly and high-quality bioinformatics tools have improved the identification of bacterial species, and bacterial resistance surveillance. The novel Citrobacter portucalensis species was proposed in 2017 after taxonomic reclassification and definition of the strain A60T isolated in 2008. Here, we presented genomic data showing the occurrence of multidrug-resistant C. portucalensis isolates carrying blaCTX-M-15 ESBL genes in South America. Additionally, we observed the intercontinental dissemination of clades harboring a broad resistome to clinically relevant antibiotics. Therefore, these findings highlight that C. portucalensis is a global MDR bacteria that carries intrinsic blaCMY- and qnrB-type genes and has become a critical priority pathogen due to the acquisition of clinically relevant resistance determinants, such as ESBL and carbapenemase-encoding genes.