Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells.

Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has significantly improved therapeutic outcomes. In line with this, our team has developed temozolomide-transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebrafish model and were able to efficiently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantification of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression-a core regulator of this apoptotic pathway. Our findings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma.

Circadian ABCG2 Expression Influences the Brain Uptake of Donepezil across the Blood-Cerebrospinal Fluid Barrier.

Donepezil (DNPZ) is a cholinesterase inhibitor used for the management of Alzheimer's disease (AD) and is dependent on membrane transporters such as ABCG2 to actively cross brain barriers and reach its target site of action in the brain. Located in the brain ventricles, the choroid plexus (CP) forms an interface between the cerebrospinal fluid (CSF) and the bloodstream, known as the blood-CSF barrier (BCSFB). Historically, the BCSFB has received little attention as a potential pathway for drug delivery to the central nervous system (CNS). Nonetheless, this barrier is presently viewed as a dynamic transport interface that limits the traffic of molecules into and out of the CNS through the presence of membrane transporters, with parallel activity with the BBB. The localization and expression of drug transporters in brain barriers represent a huge obstacle for drug delivery to the brain and a major challenge for the development of therapeutic approaches to CNS disorders. The widespread interest in understanding how circadian clocks modulate many processes that define drug delivery in order to predict the variability in drug safety and efficacy is the next bridge to improve effective treatment. In this context, this study aims at characterizing the circadian expression of ABCG2 and DNPZ circadian transport profile using an in vitro model of the BCSFB. We found that ABCG2 displays a circadian pattern and DNPZ is transported in a circadian way across this barrier. This study will strongly impact on the capacity to modulate the BCSFB in order to control the penetration of DNPZ into the brain and improve therapeutic strategies for the treatment of AD according to the time of the day.

The impact of biological clock and sex hormones on the risk of disease.

Molecular clocks are responsible for defining 24-h cycles of behaviour and physiology that are called circadian rhythms. Several structures and tissues are responsible for generating these circadian rhythms and are named circadian clocks. The suprachiasmatic nucleus of the hypothalamus is believed to be the master circadian clock receiving light input via the optic nerve and aligning internal rhythms with environmental cues. Studies using both in vivo and in vitro methodologies have reported the relationship between the molecular clock and sex hormones. The circadian system is directly responsible for controlling the synthesis of sex hormones and this synthesis varies according to the time of day and phase of the estrous cycle. Sex hormones also directly interact with the circadian system to regulate circadian gene expression, adjust biological processes, and even adjust their own synthesis. Several diseases have been linked with alterations in either the sex hormone background or the molecular clock. So, in this chapter we aim to summarize the current understanding of the relationship between the circadian system and sex hormones and their combined role in the onset of several related diseases.

Resultados obstétricos y perinatales de la enfermedad materna por COVID-19: estudio de casos y controles / Obstetric and Perinatal Outcomes of Maternal COVID-19 Disease: case-control study / Resultados obstétricos e perinatais da doença materna COVID-19: estudo de casos e controles

Introducción: las infecciones virales durante el embarazo pueden provocar complicaciones maternas y fetales. Es importante describir las repercusiones maternas y fetales de la enfermedad COVID-19. Objetivos: describir y analizar las características de las pacientes que presentaron infección a SARS-CoV-2 durante la gestación y los resultados maternos y fetales. Material y método: se realizó un estudio de casos y controles. Se incluyeron todas las pacientes embarazadas que presentaron infección por SARS-CoV-2 y que fueran hospitalizadas en una institución de asistencia privada (casos) en el período 1/3/2021 - 31/7/2021. Los controles se tomaron de pacientes embarazadas que estuvieran ingresadas en igual período de tiempo pero que resultaron negativas para las pruebas de SARS-CoV-2. Se incluyeron dos controles por cada caso. Las variables maternas consideradas fueron: trabajo de parto prematuro, diabetes gestacional, estado hipertensivo del embarazo, preeclampsia (severa o no severa), muerte fetal, restricción del crecimiento fetal, abruptio placentae. Las variables neonatales consideradas fueron: estado vital, peso del recién nacido (RN), Apgar al minuto y a los cinco minutos, necesidad de ingreso a una unidad especializada en cuidados neonatales y días de estadía. Se registraron las pruebas para COVID-19 y la condición del RN al alta. Resultados: las características demográficas maternas fueron comparables en ambos grupos. Se observaron 21 (55%) complicaciones obstétricas en el grupo casos y 117 (44,7%) en el grupo controles; OR = 4,2 (IC 95%: 1,9-9,7). Se identificaron 12 (30,8%) complicaciones neonatales en el grupo casos y 3 (3,8%) en el grupo control; OR = 11,2 (IC 95%: 2,9-42,9). El grupo casos estuvo asociado con una menor probabilidad de estar vacunados; OR = 0,3 (IC 95%: 0,13-0,75). Conclusiones: reportamos un riesgo aumentado de resultados maternos y neonatales adversos relacionados con la infección por el virus SARS-CoV-2. La vacunación confirma ser una herramienta valiosa contra esta infección viral.

Introduction: Viral infections during pregnancy can lead to maternal and fetal complications. It is important to describe the maternal and fetal implications of COVID-19 disease. Objetives: To describe and analyze the characteristics of patients who experienced SARS-CoV-2 infection during gestation, and maternal and fetal outcomes. Method: A case-control study was conducted. All pregnant patients who presented SARS-CoV-2 infection and were hospitalized in a private healthcare institution (cases) during the period 1/03/2021 - 31/07/2021 were included in the study. Controls were selected from pregnant patients who were admitted during the same time but tested negative for SARS-CoV-2. Two controls were included for each case. The maternal variables considered were preterm labor, gestational diabetes, preeclampsia, (severe or non-severe) preeclampsia, fetal death, fetal growth restriction, placental abruption. The neonatal variables considered were vital status, newborn weight, one-minute and five-minute Apgar scores, need for admission to a specialized neonatal care unit, and length of stay in days. COVID-19 tests for the newborn and their condition at discharge were recorded. Results: Maternal demographic characteristics were comparable in both groups. Twenty-one (55%) obstetric complications were observed in the case group, and 117 (44.7%) in the control group; OR= 4.2 (95% CI: 1.9-9.7). Twenty-one (30.8%) neonatal complications were observed in the case group, and 3 (3.8%) in the control group; OR= 11.2 (95% CI: 2.9-42.9). The case group was associated with a lower likelihood of being vaccinated; OR = 0.3 (95% CI: 0.13-0.75). Conclusions: We report an increased risk of adverse maternal and neonatal outcomes associated with SARS-CoV-2 virus infection. Vaccination proves to be a valuable tool against this viral infection.

Introdução: as infecções virais durante a gravidez podem causar complicações maternas e fetais. É importante descrever as repercussões maternas e fetais da COVID-19. Objetivos: descrever e analisar as características das pacientes que apresentaram infecção por SARS-CoV-2 durante a gravidez e os desfechos maternos e fetais. Material e métodos: foi realizado um estudo caso-controle. Foram incluídas todas as gestantes que apresentaram infecção por SARS-CoV-2 e que estiveram internadas em instituição privada (casos) no período de 01 de março a 31 de julho de 2021. Os controles foram pacientes grávidas hospitalizadas durante o mesmo período de tempo, mas com teste negativo para SARS-CoV-2. Dois controles foram incluídos para cada caso. As variáveis maternas consideradas foram: trabalho de parto prematuro, diabetes gestacional, estado hipertensivo da gravidez, pré-eclâmpsia (grave ou não grave), óbito fetal, restrição do crescimento fetal, descolamento prematuro da placenta. As variáveis neonatais consideradas foram: estado vital, peso do recém-nascido (RN), Apgar de um e cinco minutos, necessidade de internação em unidade especializada em cuidados neonatais e dias de internação. Os resultados dos testes para COVID-19 e a condição do recém-nascido na alta foram registrados. Resultados: As características demográficas maternas foram comparáveis em ambos os grupos. 21 (55%) complicações obstétricas foram observadas no grupo caso e 117 (44,7%) no grupo controle; OR= 4,2 (IC 95%: 1,9-9,7). 12 (30,8%) complicações neonatais foram identificadas no grupo caso e 3 (3,8%) no grupo controle; OR = 11,2 (IC 95%: 2,9-42,9). O grupo de casos foi associado a uma menor probabilidade de ser vacinado; OR = 0,3 (IC 95%: 0,13-0,75). Conclusões: Relatamos um risco aumentado de resultados maternos e neonatais adversos relacionados à infecção pelo vírus SARS-CoV-2. A vacinação confirma ser uma ferramenta valiosa contra esta infecção viral.

The Role of Biological Rhythms in New Drug Formulations to Cross the Brain Barriers.

For brain protection, the blood-brain barrier and blood-cerebrospinal fluid barrier limit the traffic of molecules between blood and brain tissue and between blood and cerebrospinal fluid, respectively. Besides their protective function, brain barriers also limit the passage of therapeutic drugs to the brain, which constitutes a great challenge for the development of therapeutic strategies for brain disorders. This problem has led to the emergence of novel strategies to treat neurological disorders, like the development of nanoformulations to deliver therapeutic agents to the brain. Recently, functional molecular clocks have been identified in the blood-brain barrier and in the blood-cerebrospinal fluid barrier. In fact, circadian rhythms in physiological functions related to drug disposition were also described in brain barriers. This opens the possibility for chronobiological approaches that aim to use time to improve drug efficacy and safety. The conjugation of nanoformulations with chronobiology for neurological disorders is still unexplored. Facing this, here, we reviewed the circadian rhythms in brain barriers, the nanoformulations studied to deliver drugs to the brain, and the nanoformulations with the potential to be conjugated with a chronobiological approach to therapeutic strategies for the brain.

Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes

Drug efficacy is dependent on the pharmacokinetics and pharmacodynamics of therapeutic agents. Tight junctions, detoxification enzymes, and drug transporters, due to their localization on epithelial barriers, modulate the absorption, distribution, and the elimination of a drug. The epithelial barriers which control the pharmacokinetic processes are sex steroid hormone targets, and in this way, sex hormones may also control the drug transport across these barriers. Thus, sex steroids contribute to sex differences in drug resistance and have a relevant impact on the sex-related efficacy of many therapeutic drugs. As a consequence, for the further development and optimization of therapeutic strategies, the sex of the individuals must be taken into consideration. Here, we gather and discuss the evidence about the regulation of ATP-binding cassette transporters by sex steroids, and we also describe the signaling pathways by which sex steroids modulate ATP-binding cassette transporters expression, with a focus in the most important ATP-binding cassette transporters involved in multidrug resistance. (AU)

Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes.

Drug efficacy is dependent on the pharmacokinetics and pharmacodynamics of therapeutic agents. Tight junctions, detoxification enzymes, and drug transporters, due to their localization on epithelial barriers, modulate the absorption, distribution, and the elimination of a drug. The epithelial barriers which control the pharmacokinetic processes are sex steroid hormone targets, and in this way, sex hormones may also control the drug transport across these barriers. Thus, sex steroids contribute to sex differences in drug resistance and have a relevant impact on the sex-related efficacy of many therapeutic drugs. As a consequence, for the further development and optimization of therapeutic strategies, the sex of the individuals must be taken into consideration. Here, we gather and discuss the evidence about the regulation of ATP-binding cassette transporters by sex steroids, and we also describe the signaling pathways by which sex steroids modulate ATP-binding cassette transporters expression, with a focus in the most important ATP-binding cassette transporters involved in multidrug resistance.

Binary Diffusion Coefficients for Short Chain Alcohols in Supercritical Carbon Dioxide-Experimental and Predictive Correlations.

Experimental binary diffusion coefficients for short-chain alcohols in supercritical carbon dioxide were measured using the Taylor dispersion technique in a temperature range of 306.15 K to 331.15 K and along the 10.5 MPa isobar. The obtained diffusion coefficients were in the order of 10-8 m2 s-1. The dependence of D on temperature and solvent density was examined together with the influence of molecular size. Some classic correlation models based on the hydrodynamic and free volume theory were used to estimate the diffusion coefficients in supercritical carbon dioxide. Predicted values were generally overestimated in comparison with experimental ones and correlations were shown to be valid only in high-density regions.

Bitter taste signaling in cancer.

Pharmacoresistance of cancer cells to many drugs used in chemotherapy remains a major challenge for the treatment of cancer. Multidrug resistance transporters, especially ATP-binding cassette (ABC) transporters, are a major cause of cancer drug resistance since they translocate a broad range of drug compounds across the cell membrane, extruding them out of the cells. The regulation of ABC transporters by bitter taste receptors (TAS2Rs), which might be activated by specific bitter tasting compounds, was described in several types of cells/organs, becoming a potential target for cancer therapy. TAS2Rs expression has been reported in many organs and several types of cancer, like breast, ovarian, prostate, and colorectal cancers, where their activation was shown to be involved in various biological actions (cell survival, apoptosis, molecular transport, among others). Moreover, many TAS2Rs' ligands, such as flavonoids and alkaloids, with well-recognized beneficial properties, including several anticancer effects, have been reported as potential adjuvants in cancer therapies. In this review, we discuss the potential therapeutic role of TAS2Rs and bitter tasting compounds in different types of cancer as a possible way to circumvent chemoresistance.

Circadian rhythmicity of amyloid-beta-related molecules is disrupted in the choroid plexus of a female Alzheimer's disease mouse model.

The choroid plexus (CP) is part of the blood-cerebrospinal fluid barrier (BCSFB) and was recently described as an important component of the circadian clock system. It is the principal source of cerebrospinal fluid (CSF) and responsible for the synthesis and secretion of various neuroprotective peptides including those involved in amyloid-ß (Aß) transport/degradation, contributing to Aß homeostasis. Inadequate Aß metabolic clearance and transport across the BCSFB have been associated with circadian dysfunctions in Alzheimer's disease (AD) patients. To investigate whether AD pathology influences Aß scavengers circadian expression, we collected CP at different time points from an AD mouse model (APP/PS1) (female and male animals, aged 6- and 12-months-old) and analyzed their mRNA expression by Real-time RT-PCR. Only angiotensin-converting enzyme (Ace) expression in 6-month-old female wild-type mice and transthyretin (Ttr) expression in 12-month-old female wild-type mice presented significant rhythmicity. The circadian rhythmicity of Ace and Ttr, prompt us to analyze the involvement of circadian rhythm in Aß uptake. A human CP papilloma (HIBCPP) cell line was incubated with Aß-488 and uptake was evaluated at different time points using flow cytometry. Aß uptake displayed circadian rhythmicity. Our results suggest that AD might affect Aß scavengers rhythmicity and that Aß clearance is a rhythmic process possibly regulated by the rhythmic expression of Aß scavengers.

Development of WRAP5 Peptide Complexes for Targeted Drug/Gene Co-Delivery toward Glioblastoma Therapy.

Despite the great progress over the past few decades in both the diagnosis and treatment of a great variety of human cancers, glioblastoma remains the most lethal brain tumor. In recent years, cancer gene therapy focused on non-viral vectors which emerged as a promising approach to glioblastoma treatment. Transferrin (Tf) easily penetrates brain cells of the blood-brain barrier, and its receptor is highly expressed in this barrier and glioblastoma cells. Therefore, the development of delivery systems containing Tf appears as a reliable strategy to improve their brain cells targeting ability and cellular uptake. In this work, a cell-penetrating peptide (WRAP5), bearing a Tf-targeting sequence, has been exploited to condense tumor suppressor p53-encoding plasmid DNA (pDNA) for the development of nanocomplexes. To increase the functionality of developed nanocomplexes, the drug Temozolomide (TMZ) was also incorporated into the formulations. The physicochemical properties of peptide/pDNA complexes were revealed to be dependent on the nitrogen to phosphate groups ratio and can be optimized to promote efficient cellular internalization. A confocal microscopy study showed the capacity of developed complexes for efficient glioblastoma cell transfection and consequent pDNA delivery into the nucleus, where efficient gene expression took place, followed by p53 protein production. Of promise, these peptide/pDNA complexes induced a significant decrease in the viability of glioblastoma cells. The set of data reported significantly support further in vitro research to evaluate the therapeutic potential of developed complexes against glioblastoma.

Temporal trend of accidents due to percutaneous exposure in a public hospital in Brazil, 2007-2019.

OBJECTIVES: to analyze the temporal trend of accidents due to percutaneous exposure in a public hospital in Brazil, between 2007 and 2019, according to sociodemographic and professional characteristics. METHODS: analysis of time series of accidents due to percutaneous exposure that occurred in health workers. Sociodemographic and professional variables, accident profile, post-accident behavior and accident incidence rates were evaluated. The Prais Winsten regression was used for trend analysis and calculation of the annual percentage change, with a significance level of 5%. RESULTS: 761 occupational accidents were recorded. There was a downward trend in the rate of percutaneous injuries among female workers (-0.012%; p=0.009), who had secondary education (-0.011%; p=0.035) and among all health professional categories (-0.010%; p =0.019). There was an increasing trend (0.018%; p= 0.050) among workers with ≥ 61 months of professional experience. CONCLUSIONS: the analysis showed a decreasing incidence of percutaneous accidents, which can be explained by multiple factors.

The Daily Expression of ABCC4 at the BCSFB Affects the Transport of Its Substrate Methotrexate.

The choroid plexuses (CPs), located in the brain ventricles, form an interface between the blood and the cerebrospinal fluid named the blood-cerebrospinal barrier, which, by the presence of tight junctions, detoxification enzymes, and membrane transporters, limits the traffic of molecules into the central nervous system. It has already been shown that sex hormones regulate several CP functions, including the oscillations of its clock genes. However, it is less explored how the circadian rhythm regulates CP functions. This study aimed to evaluate the impact of sex hormones and circadian rhythms on the function of CP membrane transporters. The 24 h transcription profiles of the membrane transporters rAbca1, rAbcb1, rAbcc1, rAbcc4, rAbcg2, rAbcg4, and rOat3 were characterized in the CPs of intact male, intact female, sham-operated female, and gonadectomized rats. We found that rAbcc1 is expressed in a circadian way in the CPs of intact male rats, rAbcg2 in the CPs of intact female rats, and both rAbcc4 and rOat3 mRNA levels were expressed in a circadian way in the CPs of intact male and female rats. Next, using an in vitro model of the human blood-cerebrospinal fluid barrier, we also found that methotrexate (MTX) is transported in a circadian way across this barrier. The circadian pattern of Abcc4 found in the human CP epithelial papilloma cells might be partially responsible for MTX circadian transport across the basal membrane of CP epithelial cells.

The druggability of bitter taste receptors for the treatment of neurodegenerative disorders.

The delivery of therapeutic drugs to the brain remains a major pharmacology challenge. A complex system of chemical surveillance to protect the brain from endogenous and exogenous toxicants at brain barriers hinders the uptake of many compounds with significant in vitro and ex vivo therapeutic properties. Despite the advances in the field in recent years, the components of this system are not completely understood. Recently, a large group of chemo-sensing receptors, have been identified in the blood-cerebrospinal fluid barrier. Among these chemo-sensing receptors, bitter taste receptors (TAS2R) hold promise as potential drug targets, as many TAS2R bind compounds with recognized neuroprotective activity (quercetin, resveratrol, among others). Whether activation of TAS2R by their ligands contributes to their diverse biological actions described in other cells and tissues is still debatable. In this review, we discuss the potential role of TAS2R gene family as the mediators of the biological activity of their ligands for the treatment of central nervous system disorders and discuss their potential to counteract drug resistance by improving drug delivery to the brain.

The brain as a source and a target of prolactin in mammals.

Prolactin is a polypeptide hormone associated with an extensive variety of biological functions. Among the roles of prolactin in vertebrates, some were preserved throughout evolution. This is the case of its function in the brain, where prolactin receptors, are expressed in different structures of the central nervous system. In the brain, prolactin actions are principally associated with reproduction and parental behavior, and involves the modulation of adult neurogenesis, neuroprotection, and neuroplasticity, especially during pregnancy, thereby preparing the brain to parenthood. Prolactin is mainly produced by specialized cells in the anterior pituitary gland. However, during vertebrate evolution many other extrapituitary tissues do also produce prolactin, like the immune system, endothelial cells, reproductive structures and in several regions of the brain. This review summarizes the relevance of prolactin for brain function, the sources of prolactin in the central nervous system, as well as its local production and secretion. A highlight on the impact of prolactin in human neurological diseases is also provided.

The Crosstalk between Melatonin and Sex Steroid Hormones.

Melatonin, an indolamine mainly released from the pineal gland, is associated with many biological functions, namely, the modulation of circadian and seasonal rhythms, sleep inducer, regulator of energy metabolism, antioxidant, and anticarcinogenic. Although several pieces of evidence also recognize the influence of melatonin in the reproductive physiology, the crosstalk between melatonin and sex hormones is not clear. Here, we review the effects of sex differences in the circulating levels of melatonin and update the current knowledge on the link between sex hormones and melatonin. Furthermore, we explore the effects of melatonin on gonadal steroidogenesis and hormonal control in females. The literature review shows that despite the strong evidence that sex differences impact on the circadian profiles of melatonin, reports are still considerably ambiguous, and these differences may arise from several factors, like the use of contraceptive pills, hormonal status, and sleep deprivation. Furthermore, there has been an inconclusive debate about the characteristics of the reciprocal relationship between melatonin and reproductive hormones. In this regard, there is evidence for the role of melatonin in gonadal steroidogenesis brought about by research that shows that melatonin affects multiple transduction pathways that modulate Sertoli cell physiology and consequently spermatogenesis, and also estrogen and progesterone production. From the outcome of our research, it is possible to conclude that understanding the correlation between melatonin and reproductive hormones is crucial for the correction of several complications occurring during pregnancy, like preeclampsia, and for the control of climacteric symptoms.

Perfil dos exames citopatológicos do colo do útero de mulheres residentes no estado de Minas Gerais / Profile of cytopathological examinations of the cerever of women resident in the state of Minas Gerais

Introdução: O diagnóstico precoce e referenciamento ao serviço especializado são essenciais para melhorar as taxas de cura e sobrevida das mulheres acometidas pelo câncer de colo de útero. Assim, a realização deste estudo tornará possível o levantamento de informações que serão essenciais para o desenvolvimento de medidas preventivas, que almejam contribuir com o desenvolvimento de ações de educação em saúde e o diagnóstico precoce para reduzir a morbimortalidade dessa enfermidade. Objetivo: Identificar o perfil dos resultados dos exames citopatológicos do colo do útero de mulheres residentes no estado de Minas Gerais a partir dos dados de exames correspondentes ao ano de 2019, utilizando as variáveis disponibilizadas pelo Sistema de Informação do Câncer. Métodos: Trata-se de um estudo retrospectivo, exploratório, quantitativo realizado por meio de base de dados secundários. Os dados foram submetidos à análise no software SPSS, versão 20.0. Realizou-se estatística descritiva (frequência absoluta, porcentagem, média e desvio padrão). Para verificar associação entre variáveis qualitativas foi utilizado teste qui-quadrado (x²) e exato de Fisher. A força das associações entre as variáveis foi aferida pelo risco relativo (RR) e intervalos de confiança (IC 95%). Resultados: As principais alterações presentes nos exames foram: alterações por células escamosas atípicas de significado indeterminado e lesão intraepitelial de baixo grau. Após análises estatísticas, notou-se que algumas alterações possuem risco maior de se desenvolverem no público fora da faixa etária preconizada, ou seja, entre mulheres com idade <25 anos ou >64 anos. Conclusão: O estudo realizado contribui para identificação do perfil atual vivenciado na área da saúde da mulher e possibilita a criação de condutas e ações que visem intervir frente aos resultados obtidos, impactando positivamente na realidade de Minas Gerais

Introduction: Early diagnosis and referral to a specialized service are essential to improve the cure and survival rates of women affected by cervical cancer. Thus, carrying out this study will make it possible to collect information that will be essential for the development of preventive measures, which aim to contribute to the development of health education actions and early diagnosis to reduce the morbidity and mortality of this disease. Objective: Identify the profile of the results of cervical cytopathological examinations of women residing in the State of Minas Gerais from the data of examinations corresponding to the year 2019, using the variables made available by the Cancer Information System.Methods: This is a retrospective, exploratory, quantitative study carried out by means of a secondary database. The data were submitted to analysis using the SPSS software, version 20.0. Descriptive statistics (absolute frequency, percentage, mean and standard deviation) were performed. To verify the association between qualitative variables, the chi-square test (x²) and Fisher's exact test were used. The strength of the associations between the variables was measured by the relative risk (RR) and confidence intervals (95% CI). Results: The main alterations present in the cytopathological exams performed were: changes due to atypical squamous cells of undetermined significance and low- grade intraepithelial lesion. After statistical analysis, it was noted that some changes have a higher risk of developing in the public outside the recommended age range, that is, among women aged <25 years or> 64 years. Conclusion: The study carried out contributes to the identification of the current profile experienced in the area of women's health and enables the creation of conducts and actions that aim to intervene in view of the results obtained, positively impacting the reality of Minas Gerais.

Is paclitaxel less cardiotoxic in the treatment of breast cancer before or after doxorubicin? / Qual estratégia terapêutica é menos cardiotóxica no tratamento do câncer de mama: uso de paclitaxel antes ou depois da doxorrubicina?

Background: The combination of doxorubicin (DOX) with paclitaxel (PTX) effectively treats breast cancer (BC). However, DOX-associated cardiotoxicity (CTX) is aggravated by the use of PTX. Consensus is lacking about which drug sequence involves the most CTX. Objectives: To evaluate whether DOX followed by PXT or the reverse sequence has the greatest cardiotoxic potential in the treatment of BC. Methods: Prospective study of women with primary BC who received four cycles of DOX and 12 infusions of PTX. Participants were divided into Group 1 (G1; PXT before DOX) and Group 2 (G2; DOX before PXT) at the discretion of the oncologist. CTX was defined as an absolute reduction in left ventricular ejection fraction (LVEF) > 10% to a value <53%. Patients underwentclinical evaluations and echocardiography before treatment (Phase 1) and one year after treatment (Phase 2). Results: Sixty-nine women were evaluated: 19 in G1 and 50 in G2. The groups had similar clinical characteristics. The doses of radiation, DOX, and PTX used were similar. Eight (11.6%) patients developed CTX: two (10.5%) in G1 and six (12.0%) in G2 (p=0.62). The mean LVEF was similar between groups in Phase 1 (G1=65.1±3.5%; G2=65.2±3.9%; p=0.96), with a significant reduction noted after one year in both groups: G1=61.4±8.1% (p=0.021) and G2=60.8±7.6% (p<0,001). Although lower, mean LVEF remained similar between groups after Phase 2 (p=0.79). Conclusions: In women with BC who underwent chemotherapy, the incidence of CTX at the end of the first year of treatment was similar regardless of whether DOX was used before or after PTX. (AU)