Maternal low-dose caffeine intake during the perinatal period promotes short- and long-term sex-dependent hormonal and behavior changes in the offspring.

AIM: Maternal caffeine crosses the placenta and mammary barriers, reaching the baby and, because his/her caffeine metabolism is immature, our hypothesis is that even a low caffeine intake (250 mg/day), lower than the dose limit recommended by the World Health Organization, can promote caffeine overexposure in the offspring, leading to short- and long-term changes. MAIN METHODS: Pregnant Wistar rats received intragastric caffeine (CAF) (25 mg/Kg/day) or vehicle during the gestation and lactation periods. We evaluated morphometrical, metabolic, hormonal, and behavioral parameters of male and female offspring at different ages. KEY FINDINGS: Even a low caffeine intake promoted lower maternal body mass and adiposity, higher plasma cholesterol and lower plasma T3, without changes in plasma corticosterone. Female CAF offspring exhibited lower birth weight, body mass gain and food intake throughout life, and hyperinsulinemia at weaning, while male CAF offspring showed reduced food intake and lower plasma T3 at weaning. At puberty and adulthood, male CAF showed higher preference for palatable food, aversion to caffeine intake and higher locomotor activity, while female CAF only showed lower preference for high fat diet (HFD) and lower anxiety-like behavior. At adulthood, both male and female offspring showed higher plasma T3. Male CAF showed hypertestosteronemia, while female CAF showed hypoinsulinemia without effect on glucose tolerance. SIGNIFICANCE: A low caffeine intake during the perinatal period affects rat's offspring development, promoting sex-dependent hormonal and behavior changes. Current data suggest the need to review caffeine recommendations during the perinatal period.

Pre-Exposure Prophylaxis to Prevent Hematophagous Bat-Mediated Rabies Outbreaks in Remote Amazon Communities: Lessons from a Pilot for Public Health Policy.

In 2018, an outbreak of human rabies caused by the hematophagous bat Desmodus rotundus hit the Brazilian Amazon Basin community of Melgaço, Brazil, resulting in the death of 10 people, 9 of them children. The incidence of rabies has been on the rise among populations in conditions of vulnerability in this ecosystem due to human expansion into sylvatic environments and limited access to public health services. To address this issue, in September 2019, a collaborative effort from national, local, and international institutions promoted and executed a pilot for pre-exposure prophylaxis of a population in high-risk areas for hematophagous bat-mediated rabies. This measure is usually only implemented in response to outbreaks. The pilot was conducted in Portel, in a nearby location to the previous outbreak, with the use of fluvial transportation, and 2987 individuals in 411 dwellings were successfully vaccinated. It established a methodology for pre-exposure prophylaxis for populations in conditions of vulnerability, identifying logistics and costs, as well as characterizing the target riverine population regarding risk factors associated with bites by hematophagous bats. This approach offers a proactive measure to prevent future outbreaks and provides valuable insights into how to address the issue of rabies in remote and difficult-to-reach areas.

Parents' Perspectives on Early Relational Health: A Qualitative Study.

OBJECTIVE: The American Academy of Pediatrics endorses a paradigm shift toward promoting early relational health (ERH) in pediatrics. Pediatric clinicians have a unique opportunity to promote ERH, yet little work has sought parents' perspectives on how clinicians can do so effectively. We sought to understand diverse parents' perspectives on ERH and the role of pediatric clinicians in supporting it. METHODS: We conducted virtual focus groups using a guide prepared with input from community partners and parent advisors. We purposively sampled a diverse group of parents of children aged ≤7 years. Focus groups were recorded and transcribed verbatim. We analyzed data as it was collected and identified themes using an inductive and iterative process. RESULTS: Thirty-seven parents participated in 8 focus groups (median parent age: 36.0 years; 43.2% Asian, 18.9% Black/African-American; 32.4% Hispanic/Latino; 78.4% mothers). We identified 3 organizing themes: (1) Time, attention, and open communication with children lay a foundation for ERH; (2) Pediatric clinicians have an opportunity to promote ERH, but disconnected parent-clinician relationships are a major barrier; and (3) Enhanced communication and careful attention to child development and family well-being represent key opportunities to strengthen parent-clinician relationships. CONCLUSION: Parents identified time, attention, and open communication as essential to ERH. Although participants expressed openness to clinicians addressing ERH, such work is contingent on strong parent-clinician relationships. Policymakers and clinicians seeking to address ERH in pediatric settings must also be prepared to address potential barriers through strategies like providing adequate time to facilitate relationship-building and careful attention to address this critical topic.

Exercise effects on cortical excitability in pain populations: A systematic review and meta-analysis.

BACKGROUND: Transcranial Magnetic Stimulation (TMS) studies examining exercise-induced neuroplasticity in pain populations have produced contradictory findings. We conducted a systematic review to explore how exercise impacts cortical excitability in pain populations using TMS metrics. This review aims to summarize the effect sizes and to understand their sources of heterogeneity. METHODS: We searched multiple databases from inception to December 2022. We included randomized controlled trials (RCTs) with any type of pain population, including acute and chronic pain; exercise interventions were compared to sham exercise or other active interventions. The primary outcomes were TMS metrics, and pain intensity was the secondary outcome. Risk of bias assessment was conducted using the Cochrane tool. RESULTS: This review included five RCTs (n = 155). The main diagnoses were fibromyalgia and cervical dystonia. The interventions included submaximal contractions, aerobic exercise, physical therapy, and exercise combined with transcranial direct current stimulation. Three studies are considered to have a high risk of bias. All five studies showed significant pain improvement with exercise. The neurophysiological data revealed improvements in cortical excitability measured by motor-evoked potentials; standardized mean difference = 2.06, 95% confidence interval 1.35-2.78, I2 = 19%) but no significant differences in resting motor threshold. The data on intracortical inhibition/facilitation (ICI/ICF) was not systematically analyzed, but one study (n = 45) reported higher ICI and lower ICF after exercise. CONCLUSIONS: These findings suggest that exercise interventions positively affect pain relief by modifying corticospinal excitability, but their effects on ICI/ICF are still unclear. While the results are inconclusive, they provide a basis for further exploration in this area of research; future studies should focus on establishing standardized TMS measurements and exercise protocols to ensure consistent and reliable findings. A large-scale RCT that examines various exercise interventions and their effects on cortical excitability could offer valuable insights to optimize its application in promoting neuroplasticity in pain populations.

Repetitive dynamic matrix control for systems with periodic specifications.

This paper proposes a Repetitive Dynamic Matrix Control (RDMC) for systems with periodic specifications. The new algorithm is able to track periodic references and reject repetitive disturbances with a known period based on a modified prediction error. A repetitive version of the Generalized DMC (GDMC) is also proposed such that it can be applied to control open-loop unstable systems. Only the step-response coefficients are required to describe the dynamical system such that the RDMC preserves the modeling simplicity of the Dynamic Matrix Control (DMC). The proposed solution can be interpreted as an extension of the DMC for repetitive control applications. A data-driven filter design is proposed in order to ensure null prediction steady-state error in the presence of periodic disturbances even for unstable open-loop systems. Two case studies are presented to show the usefulness of the proposed strategy for control systems with periodic specification and to illustrate the typical advantages and drawbacks of the proposed repetitive control extension of the DMC algorithm.

Brain compensatory mechanisms in depression and memory complaints in fibromyalgia: the role of theta oscillatory activity.

BACKGROUND: The different clinical presentations of fibromyalgia syndrome (FMS) might play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in patients with FMS. Understanding how these clinical presentations are associated with the clinical and neurophysiological aspects of FMS is important for the development of effective treatments. AIM: To explore the relationship of memory complaints and depressive symptoms with the different clinical and neurophysiological characteristics of FMS. METHODS: Cross-sectional data analysis from a randomized clinical trial. Baseline demographics and data on physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) from 63 subjects with FMS were used. Multiple linear and logistic association models were constructed. RESULTS: Final regression models including different sets of predictions were statistically significant (P < .001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poorer sleep quality, lower motor threshold, and higher relative theta power in the central area and were more likely to have clinical depression. Higher anxiety, pain, and theta power were associated with a higher likelihood of memory complaints. CONCLUSION: Depression symptoms seem to be associated with transcranial magnetic stimulation-indexed motor threshold and psychosocial variables, whereas memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms might be catalyzed or triggered by some behavioral and clinical features, such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests that the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment of FMS. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03371225.

Maternal exposure to tributyltin alters the breast milk, hormonal profile, and thyroid morphology of dams and induces sex-specific changes in neonate rat offspring.

Tributyltin (TBT) is the chemical substance commonly used worldwide to prevent biofouling of vessels. Due to its ability to bioaccumulate and biomagnify, even after being banned, significant concentrations of TBT can be detected in sediment, affecting marine and human life. Although studies have shown that direct exposure to TBT alters physiological parameters in mammals, the relationship between exposure to TBT during pregnancy and lactation, considered critical windows for metabolic programming, has not been fully elucidated. Our hypothesis is that offspring whose mothers were exposed to TBT during critical stages of development may exhibit dysfunctions in endocrine-metabolic parameters. We used pregnant Wistar rats that were divided into groups and received the following treatments from gestational day 7 until the end of lactation by intragastric gavage: vehicle (ethanol 0.01%; Control), low TBT dose (100 ng/kg of body weight (bw)/day; TBT100ng) and high TBT dose (1000 ng/kg bw/day; TBT1000ng). Dams and offspring at birth and weaning (21 days old) were studied. Maternal exposure to TBT promoted dose-dependent changes in dams. The findings for adiposity, milk composition and lipid profile were more pronounced in TBT100 ng dam; however, thyroid morphology was altered in TBT1000 ng dam. Female offspring were differentially affected by the dose of exposure. At birth, females in the TBT100ng group had low body weight, lower naso-anal length (NAL), and higher plasma T4, and at weaning, females in the TBT100ng group had lower insulin and leptin levels. Females in the TBT1000ng group had lower NAL at birth and lower leptinemia and weight of white adipose tissue at weaning. Male offspring from TBT groups showed high T3 at birth, without biometric alterations at birth or weaning. Despite these findings, both sexes exhibited dose-dependent morphological changes in the thyroid gland. Thus, maternal exposure to TBT constitutes an important route of contamination for both dams and offspring.

Livestock and environmental characterization of Colombian municipalities: study of vesicular stomatitis.

Amid the surge in data volume generated across various fields of knowledge, there is an increasing necessity for advanced analytical methodologies to effectively process and utilize this information. Particularly in the field of animal health, this approach is pivotal for enhancing disease understanding, surveillance, and management. The main objective of the study was to conduct a comprehensive livestock and environmental characterization of Colombian municipalities and examine their relationship with the distribution of vesicular stomatitis (VS). Utilizing satellite imagery to delineate climatic and land use profiles, along with data from the Colombian Agricultural Institute (ICA) concerning animal populations and their movements, the research employed Principal Component Analysis (PCA) to explore the correlation between environmental and livestock-related variables. Additionally, municipalities were grouped through a Hierarchical Clustering process. The assessment of risk associated with VS was carried out using a Generalized Linear Model. This process resulted in the formation of four distinct clusters: three primarily characterized by climatic attributes and one predominantly defined by livestock characteristics. Cluster 1, identified as "Andino" due to its climatic and environmental features, exhibited the highest odds ratio for VS occurrence. The adopted methodology not only provides a deeper understanding of the local population and its context, but also offers valuable insights for enhancing disease surveillance and control programs.

A comparative approach employing microCT for the analysis of Cenozoic foraminifera from the Brazilian carbonate equatorial platform.

Worldwide, some of the largest hydrocarbon reservoirs are located in tropical neritic carbonate deposits. Biostratigraphic and paleoenvironmental analyzes of these sedimentary records are often based on the study of foraminiferal assemblage. Foraminifera-based biozones are widely employed in the oil industry to support drilling processes that, alongside petrophysical prospecting, define interval favorable for exploiting hydrocarbon resources. Both scientific research and the petroleum industry, however, usually apply traditional petrographical and paleontological methods to analyze microfossil assemblages, especially for large benthic foraminifera. New, faster, and more accurate methods based on microCT analyzes have emerged as a valuable high-output tool to obtain high-resolution microfossil records for biostratigraphy and paleoenvironmental reconstructions. This method is also useful for the development of digital databases for artificial intelligence applications. MicroCT analyzes, therefore, lead to faster identification of foraminifera assemblage and support digital access to international foraminifera repositories and reference collections, introducing a new dimension in micropaleontological research.

Description of a new fossil Thelyphonida (Arachnida, Uropygi) and further record of Cratosolpuga wunderlichi Selden, in Selden and Shear, 1996 (Arachnida, Solifugae) from Crato Formation (Aptian/Albian), Araripe Basin, Brazil.

Background: A new fossil species of whipscorpion, Mesoproctus rayoli n. sp., is described. The specimen originates from the Crato Formation, dating to the Lower Cretaceous (Aptian/Albian) period within the Araripe Sedimentary Basin. This species has been provisionally assigned to Mesoproctus Dunlop, 1998, as it represents the sole known Thelyphonida fossil genus discovered in South America and within Araripe Lagerstätte. Methods: The material underwent detailed description and illustration processes. Key diagnostic characters, such as body length, pedipalpal coxae apophysis, the form of the opisthosoma, and the length of leg IV, were meticulously examined. SEM methods were applied in this study. Results: Through the detailed analysis, comparisons and differences to Mesoproctus rowlandi Dunlop, 1998 were made possible. Additionally, a well-preserved specimen of the rare camel spider, Cratosolpuga wunderlichi Selden, in Selden and Shear, 1996, was identified from the limestones of the Crato Formation. The newly discovered fossil specimen of Cratosolpuga wunderlichi suggests two characters not previously described: (i) a segmented tarsomere on leg IV; and (ii) a leg I with one tarsal claw.

The use of fiberglass posts in dentistry: a literature review / O uso de pinos de fibra de vidro na odontologia: uma revisão de literatura

The choice of retaining material that will replace the lost properties of the tooth, in which it is fragile and with loss of dentin structure, is important. The success of the treatment will depend on the qualities presented in it. Therefore, the objective of this work, through a literature review, is to present the advantages and disadvantages observed in the use of fiberglass post intraradicular retainer. This paper reviews the most relevant articles on the specificities presented in the fiberglass post retaining material, published in the period (2003 to 2020). The bibliographic search was performed in PubMed, Lilacs, Scielo, Google Scholar databases. In view of the selected articles on the subject, it is possible to observe the authors' acceptance of the application of the use of retainers, highlighting that in the treatment of cases with extensive coronary destruction, the aim is to have the functional and retentive capacity returned, in addition to the tension resistance. Therefore, theThe use of fiberglass posts in weakened teeth is effective as the material of choice. In cases that require reconstruction and return of tissue integrity, it has sufficient advantages for its selection. Despite the disadvantages it has, these do not outweigh the benefits to the point of making its use unfeasible. However, knowing when, where and how to treat is always important in any procedure for a satisfactory final outcome.

A escolha do material retentor que irá substituir as propriedades perdidas do dente, no qual este se apresenta de forma fragilizada e com perca de estrutura dentinária é importante. O sucesso do tratamento irá depender das qualidades apresentadas no mesmo. Sendo assim, o objetivo deste trabalho por meio de uma revisão de literatura é apresentar as vantagens e desvantagens observadas no uso do retentor intrarradicular de pino de fibra de vidro. Este trabalho revisa os artigos mais relevantes sobre as especificidades apresentadas no material retentor de pino de fibra de vidro, publicadas no período (2003 até 2020). A busca bibliográfica foi realizada nos bancos de dados PubMed, Lilacs, Scielo, Google Scholar. Diante dos artigos selecionados referentes ao tema, pode-se observar a aceitação dos autores sobre a aplicação do uso de retentores, destacando-se que no tratamento de casos com destruição coronária extensa o intuito é dispor da devolução da capacidade funcional, retentiva, além da resistência a tensão. Portanto, a utilização de pinos de fibra de vidro em dentes fragilizados apresenta efetividade como material de escolha. Em casos que necessitam de reconstrução e devolução de sua integridade tecidual, possui consigo vantagens suficientes para sua seleção. Apesar das desvantagens que possui, essas não se sobrepõem aos benefícios a ponto de tornarem inviáveis ao seu uso. Entretanto, saber quando, onde e como tratar é sempre importante em qualquer procedimento para um desfecho final satisfatório.

Hematological profile of healthy Thoroughbred foals from birth to one month of age in Trinidad, West Indies.

OBJECTIVE: This study aimed to develop a sound database for the hematological reference intervals of thoroughbred foals in Trinidad, West Indies from birth to 1 month of age. ANIMALS: 89 foals. METHODS: Whole blood samples were taken from 89 foals throughout Trinidad at approximately 1 day, 1 week, and 1 month of age. These foals were examined to be classified as healthy or free from disease. Complete blood count (CBC), microscopic analysis of blood smears, and conventional PCR for Theileria equi and Babesia caballi were performed. RESULTS: Of the 89 foals, 67 were deemed healthy and suitable for establishing reference intervals. Foals in this study had lower mean hemoglobin and hematocrit values for all 3 times of sampling when compared to their North American counterparts. Age had a significant effect on hemoglobin, hematocrit, white blood cell (WBC), neutrophil, and platelet counts of the foals from birth to 1 month of age. CLINICAL RELEVANCE: Variations in reference intervals can occur due to differences in demographic, physiological, and environmental factors such as age, gender, breed, and geographical location. Given the changes in the hematological values over time, this study provides clinicians with valuable information that can be used to monitor the health status of newborn foals and detect disease conditions.

Maximizing the impact of reach out and read literacy promotion:anticipatory guidance and modeling.

BACKGROUND: Reach Out and Read (ROR) is a multi-component pediatric literacy promotion intervention. However, few studies link ROR components to outcomes. We examine associations between receipt of (1) multiple ROR components and (2) clinician modeling, a potential best practice, with enhanced home literacy environments (EHLEs) among Latino families. METHODS: We conducted secondary analyses of cross-sectional enrollment data from a randomized clinical trial at three urban community health centers between November 2020 and June 2023. Latino parents with infants 6-<9 months old were surveyed about ROR component receipt (children's book, anticipatory guidance, modeling) and EHLE (StimQ2- Infant Read Scale). We used mixed models with clinician as a random effect, adjusting for covariates. RESULTS: 440 Latino parent-infant dyads were included. With no components as the reference category, receipt of 1 component was not associated with EHLE. Receipt of 2 components (standardized beta = 0.27; 95%CI: 0.12-0.42) and 3 components (standardized beta = 0.33; 95% CI: 0.19-0.47) were associated with EHLE. In separate analyses, modeling was associated with EHLE (standardized beta = 0.16; 95%CI: 0.06-0.26). CONCLUSION: Findings support modeling as a core ROR component. Programs seeking to enhance equity by promoting EHLE should utilize such strategies as anticipatory guidance and clinician modeling in addition to book distribution. IMPACT: Reach Out and Read, a multi-component literacy promotion intervention, leverages primary care to promote equity in children's early language experiences. However, few studies link Reach Out and Read components to outcomes. Among Latino parent-infant dyads, we found that implementation of two and three components, compared to none, was associated with enhanced home literacy environments, following a dose response pattern. Parent report of clinician modeling was associated with enhanced home literacy environments. Literacy promotion programs seeking to enhance equity by promoting enhanced home literacy environments should utilize strategies in addition to book distribution, including anticipatory guidance and modeling, to maximize impact.

Connect: Cultivating Academic-Community Partnerships to Address Our Communities' Complex Needs During Public Health Crises.

BACKGROUND: Black and Latino communities have been disproportionately impacted by coronavirus disease 2019 and we sought to understand perceptions and attitudes in four heavily impacted New Jersey counties to develop and evaluate engagement strategies to enhance access to testing. OBJECTIVE: To establish a successful academic/community partnership team during a public health emergency by building upon longstanding relationships and using principles from community engaged research. METHODS: We present a case study illustrating multiple levels of engagement, showing how we successfully aligned expectations, developed a commitment of cooperation, and implemented a research study, with community-based and health care organizations at the center of community engagement and recruitment. LESSONS LEARNED: This paper describes successful approaches to relationship building including information sharing and feedback to foster reciprocity, diverse dissemination strategies to enhance engagement, and intergenerational interaction to ensure sustainability. CONCLUSIONS: This model demonstrates how academic/community partnerships can work together during public health emergencies to develop sustainable relationships.

Development of a Melting-Curve-Based Multiplex Real-Time PCR Assay for the Simultaneous Detection of Viruses Causing Respiratory Infection.

The prompt and accurate identification of the etiological agents of viral respiratory infections is a critical measure in mitigating outbreaks. In this study, we developed and clinically evaluated a novel melting-curve-based multiplex real-time PCR (M-m-qPCR) assay targeting the RNA-dependent RNA polymerase (RdRp) and nucleocapsid phosphoprotein N of SARS-CoV-2, the Matrix protein 2 of the Influenza A virus, the RdRp domain of the L protein from the Human Respiratory Syncytial Virus, and the polyprotein from Rhinovirus B genes. The analytical performance of the M-m-qPCR underwent assessment using in silico analysis and a panel of reference and clinical strains, encompassing viral, bacterial, and fungal pathogens, exhibiting 100% specificity. Moreover, the assay showed a detection limit of 10 copies per reaction for all targeted pathogens using the positive controls. To validate its applicability, the assay was further tested in simulated nasal fluid spiked with the viruses mentioned above, followed by validation on nasopharyngeal swabs collected from 811 individuals. Among them, 13.4% (109/811) tested positive for SARS-CoV-2, and 1.1% (9/811) tested positive for Influenza A. Notably, these results showed 100% concordance with those obtained using a commercial kit. Therefore, the M-m-qPCR exhibits great potential for the routine screening of these respiratory viral pathogens.

Metarhizium carneum Formulations: A Promising New Biological Control to Be Incorporated in the Integrated Management of Meloidogyne enterolobii on Tomato Plants.

The increase in the populations of root-knot nematode Meloidogyne enterolobii in various vegetables such as tomatoes grown under greenhouse conditions as well as increasing restrictions on the use of certain chemical nematicides have led to the search for new, effective management strategies, preferably ones that are sustainable biological alternatives. In this work, two formulations of the nematophagous fungus Metarhizium carneum, one concentrated suspension and one wettable powder, were evaluated under greenhouse conditions to reduce the M. enterolobii infestation in tomato plants. In addition, the effectiveness of the liquid formulation of M. carneum was compared with two biological and three chemical commercial nematicides. The results show that the two M. carneum formulations reduced the M. enterolobii population density by 78 and 66% in relation to the control treatment. In comparison, the liquid formulation of M. carneum and Purpureocillium lilacinum treatments reduced nematode population density by 72 and 43%, respectively, while for metam sodium preplanting applications followed by M. carneum applications during the tomato growth stage, the reduction was 96%. The alternate use of some chemical compounds plus the application of M. carneum as a biocontrol is a good starting strategy for managing M. enterolobii populations. These results confirm that M. carneum is a serious candidate for the short-term commercialization of an environmentally friendly biological nematicide.

110-million-years-old fossil suggests early parasitism in shrimps.

Direct evidence of paleo-parasitism in crustaceans is very scarce. Epicaridean isopods are obligatory parasites of crustaceans, including decapods such as crabs, shrimps, and lobsters. Their interaction with hosts is known from fossils as far back as the Jurassic through deformations of the branchial cuticle on the hosts. Their small size and low fossilization potential, outside of those larvae that have been found in amber, makes understanding the group's evolution challenging. Here, we report the oldest evidence of paleo-parasitism in marine shrimps and an imprint of a putative adult parasite that appears to be an epicaridean isopod. Our results suggest that the parasite-host interaction between epicaridean isopods and marine shrimps started at least 110 million years ago, and the Tethys Sea was a possible dispersal pathway for this lineage of parasites during the Jurassic and Cretaceous, as known for other marine organisms through most of the Mesozoic and Cenozoic. The oldest fossil records of bopyrid swellings associated with a large number of decapods from the Jurassic in Europe suggest that the Tethys region was a center of epicaridean distribution as a whole. Recent parasitic isopods found on dendrobranchiate shrimps are restricted to the Indo-Pacific and may represent a relict group of a lineage of parasites more widely distributed in the Mesozoic.

Curcumin and melphalan cotreatment induces cell cycle arrest and apoptosis in MDA-MB-231 breast cancer cells.

Breast cancer is the second most common type of cancer worldwide and the leading cause of cancer death in women. Dietary bioactive compounds may act at different stages of carcinogenesis, including tumor initiation, promotion, and progression. Spices have been used for thousands of years and have many bioactive compounds with chemopreventive and chemotherapeutic properties. Curcumin has a multitude of beneficial biological properties, including anti-inflammatory and anticancer effects. This study investigated the effects of cotreatment with curcumin and the chemotherapeutic drug melphalan in cultured MDA-MB-231 breast cancer cells. When used alone, both curcumin and melphalan had a cytotoxic effect on breast cancer cells. Combined treatment with 11.65 µM of curcumin and 93.95 µM of melphalan (CURC/MEL) reduced cell viability by 28.64% and 72.43% after 24 h and 48 h, respectively. CURC/MEL reduced the number of colony-forming units and increased ROS levels by 1.36-fold. CURC/MEL alter cell cycle progression, induce apoptosis, and upregulate caspases-3, -7, and -9, in MDA-MB-231 cells. Cotreatment with curcumin and melphalan have anti-breast cancer cells effects and represent a promising candidate for clinical testing.

Exploring regional disparities in lung cancer mortality in a Brazilian state: A cross-sectional ecological study.

BACKGROUND: Lung cancer (LC) is one of the main causes of mortality in Brazil; geographic, cultural, socioeconomic and health access factors can affect the development of the disease. We explored the geospatial distribution of LC mortality, and associated factors, between 2015 and 2019, in Parana state, Brazil. METHODS AND FINDINGS: We obtained mortality (from the Brazilian Health Informatics Department) and population rates (from the Brazilian Institute of Geography and Statistics [IBGE]) in people over 40 years old, accessibility of oncology centers by municipality, disease diagnosis rate (from Brazilian Ministry of Health), the tobacco production rate (IBGE) and Parana Municipal Performance Index (IPDM) (from Parana Institute for Economic and Social Development). Global Moran's Index and Local Indicators of Spatial Association were performed to evaluate the spatial distribution of LC mortality in Parana state. Ordinary Least Squares Regression and Geographically Weighted Regression were used to verify spatial association between LC mortality and socioeconomic indicators and health service coverage. A strong spatial autocorrelation of LC mortality was observed, with the detection of a large cluster of high LC mortality in the South of Parana state. Spatial regression analysis showed that all independent variables analyzed were directly related to LC mortality by municipality in Paraná. CONCLUSIONS: There is a disparity in the LC mortality in Parana state, and inequality of socioeconomic and accessibility to health care services could be associated with it. Our findings may help health managers to intensify actions in regions with vulnerability in the detection and treatment of LC.