Knowledge, attitudes and practice on sudden infant death: study protocol of a scoping review.

INTRODUCTION: Sudden infant death syndrome (SIDS) is the unexpected death of an infant less than 1 year old, which occurs without presentation of any signs of mortality risk and it is not explained even after investigation, necropsy and review of the site of death. The nurse is an essential healthcare professional working with children and families who can contribute to preventing avoidable deaths of infants. Because SIDS is preventable, permanent education of the healthcare team, family members and infant caregivers is necessary. OBJECTIVE: To explore the scientific literature about knowledge, attitudes and practice on SIDS. METHODS AND ANALYSIS: A scoping review will be conducted. Quantitative or qualitative primary studies, theses, dissertations and technical and governmental documents in English, Spanish, French or Portuguese will be considered, without a time limit for selection with search, in the databases: Pubmed, Embase, Scopus, Virtual Health Library, Digital Library of Theses and Dissertations of the Brazilian Institute and Cochrane. A search strategy will be elaborated with the keywords in the following themes: knowledge, attitudes, practice, sudden infant death and healthcare. The eligibility criteria will be applied to references of selected articles to identify new studies. The studies selected will be subjected to thematic content analysis, which allows data interpretation through a systematic classification process for coding themes to the analysis of quantitative and qualitative studies and meta-aggregation. NVIVO V.14 software will be used to organise, code and validate the data. ETHICS AND DISSEMINATION: Ethics approval is not required. The results will be disseminated to the health science community through professional networks, conference presentations and publication in a scientific journal.

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.

Cardiac hypertrophy that affects hyperthyroidism occurs independently of the NLRP3 inflammasome.

Cardiac hypertrophy (CH) is an adaptive response to maintain cardiac function; however, persistent stress responses lead to contractile dysfunction and heart failure. Although inflammation is involved in these processes, the mechanisms that control cardiac inflammation and hypertrophy still need to be clarified. The NLRP3 inflammasome is a cytosolic multiprotein complex that mediates IL-1ß production. The priming step of NLRP3 is essential for increasing the expression of its components and occurs following NF-κB activation. Hyperthyroidism triggers CH, which can progress to maladaptive CH and even heart failure. We have shown in a previous study that thyroid hormone (TH)-induced CH is linked to the upregulation of S100A8, leading to NF-κB activation. Therefore, we aimed to investigate whether the NLRP3 inflammasome is involved in TH-induced CH and its potential role in CH pathophysiology. Hyperthyroidism was induced in NLRP3 knockout (NLRP3-KO), Caspase-1-KO and Wild Type (WT) male mice of the C57Bl/6J strain, aged 8-12 weeks, by triiodothyronine (7 µg/100 g BW, i.p.) administered daily for 14 days. Morphological and cardiac functional analysis besides molecular assays showed, for the first time, that TH-induced CH is accompanied by reduced NLRP3 expression in the heart and that it occurs independently of the NLRP3 inflammasome and caspase 1-related pathways. However, NLRP3 is important for the maintenance of basal cardiac function since NLRP3-KO mice had impaired diastolic function and reduced heart rate, ejection fraction, and fractional shortening compared with WT mice.

Análise de custo de sequência de tratamento de câncer de ovário avançado, HRD/ BRCAwt, sob a perspectiva do sistema de saúde suplementar brasileiro / Cost Analysis of advanced ovarian cancer treatment sequence, HRD/BRCAwt from the Brazilian supplementary healthcare system perspective

Objetivo: Estimar o custo da sequência de tratamento considerando as terapias com niraparibe e bevacizumabe, respectivamente, como terapias de manutenção de 1L e 2L para pacientes com câncer de ovário (CO) epitelial com deficiência de recombinação homóloga (HRD) e BRCA selvagem (BRCAwt) em um horizonte temporal de cinco anos, sob a perspectiva do sistema de saúde suplementar brasileiro. Métodos: Foi desenvolvido um modelo de sobrevida particionado com três transições de estados de saúde, considerando os seguintes regimes em 1L e 2L, respectivamente: carboplatina + paclitaxel seguido de terapia de manutenção com niraparibe; carboplatina + gencitabina + bevacizumabe seguido pela continuação de bevacizumabe. As posologias em bula e as curvas de sobrevida livre de progressão dos respectivos estudos pivotais em cada uma das linhas terapêuticas foram utilizadas na análise, e o custo de tratamento foi calculado a partir da lista oficial de preços de medicamentos da CMED de abril de 2023. Resultados: O custo em 1L e 2L foi de BRL 868.830 e BRL 403.407, totalizando BRL 1.272.237 em um horizonte temporal de cinco anos, com 2,28 e 0,52 anos de vida livre de progressão, respectivamente, na 1L e 2L, com o total de 2,8 anos. Conclusões: O resultado da análise de custo de sequência de tratamento de câncer de ovário HRD/BRCAwt apresentou um custo total estimado de BRL 1.272.237, com 2,8 anos de vida livre de progressão. Essa análise contribui no entendimento dos custos e da eficácia esperada com o uso da terapia de manutenção de niraparibe em 1L e bevacizumabe em 2L em um horizonte temporal de cinco anos.

Objective: To estimate the cost of the treatment sequence, considering the maintenance therapies niraparib and bevacizumab, respectively, as maintenance therapies in 1L and 2L for patients with epithelial ovarian cancer with homologous recombination deficiency (HRD) and BRCA wild-type (BRCAwt) over a 5-year time horizon from the perspective of the Brazilian supplementary health system. Methods: A partitioned survival model was developed with three health state transitions, considering the following regimens in the 1L and 2L, respectively: carboplatin + paclitaxel followed by maintenance therapy with niraparib; carboplatin + gemcitabine + bevacizumab followed by the continuation of bevacizumab. The product's label and progression-free survival curves from the respective pivotal studies in each of the therapeutic lines were used in the analysis and the cost of treatment was calculated using as a reference the official CMED drug price list from April 2023. Results: The cost in 1L and 2L was BRL 868,830 and BRL 403,407, totaling BRL 1,272,237 over a 5-year period, with 2.28 and 0.52 years of progression-free survival, respectively in 1L and 2L, with a total of 2.8 years. Conclusions: The result of the analysis of the cost of the treatment sequence of ovarian cancer HRD/BRCAwt presented an estimated total cost of 1,272,237 with 2.8 year of progression-free survival. This analysis contributes to understand the expected cost and effectiveness with the use of maintenance therapy niraparib in 1L and bevacizumab in 2L over a 5-year time horizon.

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.

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.

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.

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.

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.

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.

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.