Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells.

BACKGROUND: The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. METHODS: Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. RESULTS: Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. CONCLUSION: Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

Mycobacterium tuberculosis latent infection in healthcare students: systematic review of prevalence.

OBJECTIVE: The aim of this study was to synthesize the evidence on the prevalence of latent Mycobacterium tuberculosis infection (LTBI) among undergraduate health care students. METHODS: A systematic review of prevalence with meta-analysis was conducted. Prospective and retrospective cohorts and cross-sectional studies involving probable exposure to M. tuberculosis during undergraduate education, along with the tuberculin skin test (TST) or interferon-γ release assay (IGRA) for investigation of latent tuberculosis were searched. Searches were conducted in MEDLINE, CINAHL, EMBASE, LILACS, Scopus, and Web of Science databases. Independent reviewers were responsible for the selection and inclusion of studies. Data were extracted, critically appraised, and synthesized using the JBI approach. PRISMA was used to report the study. RESULTS: Twenty-two studies were analyzed. The overall prevalence in healthcare undergraduate students was 12.53%. CONCLUSION: The prevalence of LTBI in undergraduate health students was high for such a highly educated population. Screening with TST and/or IGRA and chemoprophylaxis, when necessary, should be provided to undergraduate health students when in contact with respiratory symptomatic patients.

Use of an application on the measles vaccine for Warao indigenous refugees in Brazil.

OBJECTIVE: To evaluate the need to develop an application with information about the measles vaccine for Warao indigenous people. METHODS: This was a quantitative study conducted at the Espaço de Acolhimento Tapanã refugee shelter in the city of Belém, Pará, Brazil. The study sample was selected for convenience. Data were analyzed descriptively using Bioestat 5.0 software. RESULTS: Twenty-one Warao indigenous individuals were interviewed. It was identified that 91% (n=20) had lost their vaccination card; 91% (n=20) stated they had lost their vaccination card more than three times, and 91% expressed interest in an application to store their vaccination information. CONCLUSIONS: The research provided important information for the development of a health application named WaraoMedI (Warao Measles Diversity Indigenous), as well as offered nursing professionals evidence about the challenges Warao indigenous refugees face in self-managing their vaccination information.

Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure.

UNLABELLED: Acetaminophen (APAP) is a safe analgesic and antipyretic drug. However, APAP overdose leads to massive hepatocyte death. Cell death during APAP toxicity occurs by oncotic necrosis, in which the release of intracellular contents can elicit a reactive inflammatory response. We have previously demonstrated that an intravascular gradient of chemokines and mitochondria-derived formyl peptides collaborate to guide neutrophils to sites of liver necrosis by CXC chemokine receptor 2 (CXCR2) and formyl peptide receptor 1 (FPR1), respectively. Here, we investigated the role of CXCR2 chemokines and mitochondrial products during APAP-induced liver injury and in liver neutrophil influx and hepatotoxicity. During APAP overdose, neutrophils accumulated into the liver, and blockage of neutrophil infiltration by anti-granulocyte receptor 1 depletion or combined CXCR2-FPR1 antagonism significantly prevented hepatotoxicity. In agreement with our in vivo data, isolated human neutrophils were cytotoxic to HepG2 cells when cocultured, and the mechanism of neutrophil killing was dependent on direct contact with HepG2 cells and the CXCR2-FPR1-signaling pathway. Also, in mice and humans, serum levels of both mitochondrial DNA (mitDNA) and CXCR2 chemokines were higher during acute liver injury, suggesting that necrosis products may reach remote organs through the circulation, leading to a systemic inflammatory response. Accordingly, APAP-treated mice exhibited marked systemic inflammation and lung injury, which was prevented by CXCR2-FPR1 blockage and Toll-like receptor 9 (TLR9) absence (TLR9(-/-) mice). CONCLUSION: Chemokines and mitochondrial products (e.g., formyl peptides and mitDNA) collaborate in neutrophil-mediated injury and systemic inflammation during acute liver failure. Hepatocyte death is amplified by liver neutrophil infiltration, and the release of necrotic products into the circulation may trigger a systemic inflammatory response and remote lung injury.

Educational technology on tuberculosis: construction shared with Primary Health Care nurses.

OBJECTIVE: to develop, in a participatory way, an educational technology to assist nurses in the management of tuberculosis cases in Primary Health Care. METHODS: methodological research with a qualitative approach. Data were collected between June and October 2022, in 25 Basic Health Units, with 41 nurses interviewed individually. Thematic content analysis was carried out to guide technology elaboration. RESULTS: three empirical categories were organized, demonstrating the facilities and difficulties in tuberculosis management, the conceptions about educational technology as a facilitator of the teaching-learning process in Primary Health Care and participatory development of technology. Nurses were in favor of constructing an instructional guide technology, and made suggestions to encourage its creation and use in daily service routine. FINAL CONSIDERATIONS: the participatory process made it possible to create technology to assist nurses in the teaching-learning process in Primary Health Care about caring for people with tuberculosis.

Incidence of malaria among indigenous people associated with the presence of artisanal mining.

OBJECTIVE: To analyze the incidence of malaria among indigenous people associated with the presence of artisanal miningin the state of Pará. METHOD: Analytical, cross-sectional study conducted with 20,774 cases of malaria in indigenous people in the state of Pará (2011 to 2020). The data came from the Malaria Epidemiological Surveillance Information System, obtained from the Pará State Department of Public Health. In the analysis, Spearman's correlation coefficient was used, with a significance of 5% (p < 0.05). RESULTS: Incidence rates were high, especially in the Tapajós River Indigenous Special Health District (372.2/1,000 inhabitants). There was association between the incidence of malaria and the presence of indigenous people in artisanalmining activities on the Tapajós River (p=0.0008). CONCLUSION: The occurrence of malaria is unequal among the Special Indigenous Health Districts, being more frequent in those with greater mining activity, configuring exposure to the disease. It is necessary to adopt intersectoral measures, especially in areas of vulnerability to illness.

Social representations of pregnant women about high-risk pregnancy: repercussions for prenatal care.

OBJECTIVE: To analyze the Social Representations of pregnant women about high-risk pregnancy and its repercussions for prenatal care. METHOD: Qualitative study, based on the procedural aspect of the Theory of Social Representations, carried out with 62 high-risk prenatal pregnant women at a High Complexity Maternity, in Belém, PA, Brazil. Data from semi-structured interviews were processed by the software Interface de R pour les Analyzes Multidimensionnelles de Textes et de Questionnaires. RESULTS: Four categories emerged, in which three dimensions of the Theory composing the genesis of Social Representations are considered: the affective dimension, the biological dimension and the sociocultural dimension. CONCLUSION: Affects, negative feelings, and adaptations were revealed, with high-risk pregnancy being represented as an unusual and uncomfortable event, influenced by common sense and science, communication means, and dialogues with health professionals, with family support being considered of paramount importance. and prenatal care a propitious moment for establishing bonds with the health professional, seen as essential for their adherence to the care offered.

Human immunodeficiency virus infection in pregnant women and its correlation with socioeconomic determinants.

OBJECTIVE: To analyze the spatial pattern of human immunodeficiency virus infection in pregnant women and its correlation with socioeconomic determinants. METHOD: Ecological study, carried out with cases of human immunodeficiency virus infection in pregnant women in the state of Pará, Brazil, from 2010 to 2017. Rate analysis was performed using the empirical Bayesian method and univariate local Moran. Bivariate analyses were used to examine the correlation between infection and socioeconomic determinants. RESULTS: High rates of infection were observed in municipalities in the mesoregions of Southeast of Pará and Metropolitan area of Belém. A significant spatial correlation was found between human immunodeficiency virus infection rates in pregnant women and human development index indicators (I = 0.2836; p < 0.05), average income (I = 0.6303; p < 0.05), and illiteracy rate (I = 0.4604; p < 0.05). CONCLUSION: The spatial pattern of human immunodeficiency virus infection in pregnant women correlated to socioeconomic determinants highlights the need to restructure public policies for the control and prevention of AIDS virus that take into account the socioeconomic factors of this specific population and locoregional disparities in Pará.

Knowledge and practices about health among Quilombola men: contributions to health care.

OBJECTIVE: to analyze health knowledge and practices among Quilombola men. METHODS: a qualitative, descriptive study, carried out with 40 men from two Quilombola communities in Santa Izabel do Pará, state of Pará, Brazil. Individual interviews were carried out using a semi-structured script. Text corpus was subjected to analysis with Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires 0.6, alpha 3, through Descending Hierarchical Classification. RESULTS: among participants, eight (20.00%) were aged 55 to 59 years. 382 text segments were identified, with 299 (78.27%) being used, generating five lexical classes, which made up two subcorpora. The classes were organized into four thematic axes, covering knowledge about health and practices to prevent and solve health problems. FINAL CONSIDERATIONS: men highlighted popular/traditional wisdom permeated by biomedical knowledge, translating their understanding of how to act to remain or become healthy.

Access of people with pulmonary tuberculosis to government programs: Primary Care professionals' perceptions.

OBJECTIVE: to analyze Primary Health Care professionals' perceptions about the access of people with pulmonary tuberculosis to government social support and income transfer programs. METHODS: multicenter/qualitative study, carried out in Family Health Units in four Brazilian capitals: Belém/Pará, Campo Grande/Mato Grosso do Sul, Recife/Pernambuco and Rio de Janeiro/Rio de Janeiro. Fifty-eight professionals participated (social workers, dentists, nurses, pharmacists, physicians and nursing technicians), who provided assistance to people with pulmonary tuberculosis. Individual interviews were conducted, and the content analysis technique was used. RESULTS: among the participants, 45/77.6% were women and 33/56.9% were between 25 and 40 years old. Two thematic categories were organized, demonstrating the perceptions about the possibilities of access to government programs by people with pulmonary tuberculosis in vulnerable situations and the obstacles inherent to this context. FINAL CONSIDERATIONS: it is necessary to move forward in improving patient access to social programs.

Geospatialization of tuberculosis and income transfer programs among Indigenous peoples in an endemic territory.

OBJECTIVE: To analyze the spatial pattern of tuberculosis in Indigenous peoples from the State of Pará and its correlation with income transfer. METHODS: Ecological study, with 340 cases reported in Indigenous peoples in the State of Pará, Brazil, in the period 2016-2020. The study performed a descriptive analysis and calculation of incidence rates with smoothing by the local empirical Bayesian method. The Global Moran index assessed the autocorrelation of the rates with income transfer data, p<0,05. RESULTS: The Marajó and metropolitan mesoregions of Belém had the highest tuberculosis rates, and a reduced number of people benefited from income transfer (high-low correlation). The study identified high rates, and a significant number of people benefited from financial aid (high correlation high), I=0.399, p=0.027 in the Southwest. CONCLUSIONS: The spatial autocorrelation between tuberculosis and access to income transfer programs constitutes a relevant subsidy for the formulation of social protection policies and may impact the disease control actions in Indigenous territories, valuing the epidemiological heterogeneity identified in the mesoregions.

Temporal and Spatial Analysis Techniques as Potential Tools for Combating the HIV Epidemic among Young Brazilian Amazonian People: An Ecological Study.

BACKGROUND: The main goal of this study was to analyze the HIV epidemic temporally and spatially among young people living in Pará, Brazil, from 2007 to 2018. METHODS: For the temporal analysis, we employed an integrated autoregression of moving averages model associated with the seasonal trend using the LOESS decomposition method, which allowed for predictions to be made. In the spatial analysis, the techniques of autocorrelation, spatial and spatio-temporal risk analysis, and geographically weighted regression were used. RESULTS: During the study period, there were 8143 notifications of HIV/AIDS cases. The temporal prediction indicated a trend of growth in the incidence rate in the 20-24-year-old group from January 2019 to December 2022 and a trend of stability in the 15- to 19-year-old and 25- to 29-year-old groups. There was a territorial expansion of the HIV epidemic in Pará. Novo Progresso and the Metropolitan Region of Belém (RMB) were the zones with the highest spatial and spatio-temporal risk for HIV. Social determinants including the Basic Education Development Index, the number of physicians per 10,000 inhabitants, and the municipal high school abandonment rate in the municipalities were associated with the risk of HIV/AIDS among young people in Pará. CONCLUSIONS: To eliminate HIV among young people in Pará, the access to treatment, diagnosis, and preventive healthcare services should be expanded. Sexual and reproductive health education should be reinforced in schools and communities. Furthermore, it is necessary to promote social equity and fight HIV stigma.

Access to government social programs and the tuberculosis control program: a multicenter study.

OBJECTIVES: to analyze government social initiatives aimed at people with tuberculosis and the possibilities of access to government social programs and income transfers through the perception of tuberculosis program managers. METHODS: descriptive, qualitative study with 19 managers from Belém, Recife, Campo Grande, and Rio de Janeiro, Brazil. Thematic content analysis was used. RESULTS: there is no specific government social support for people with tuberculosis; the benefits are intended for people in social vulnerability. There are partnerships between the institutions of the secondary social healthcare network, social assistance, and community institutions. FINAL CONSIDERATIONS: the support of official bodies is important for the control of tuberculosis; however, the profile of people's vulnerability is a determining factor for access to/destination of resources from these government social support programs.

Cardioprotective effects of exercise training on doxorubicin-induced cardiomyopathy: a systematic review with meta-analysis of preclinical studies.

Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Trained DOX-treated animals improved 7.40% (95% CI 5.75-9.05, p < 0.001) in FS vs. sedentary animals. Subgroup analyses revealed a superior effect of exercise training execution prior to DOX exposure (MD = 8.20, 95% CI 6.27-10.13, p = 0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was also associated with superior effect size in FS (MD = 7.89, 95% CI 6.11-9.67, p = 0.020) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, gender and cumulative DOX dose did were not individually associated with changes on FS. Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.

Knowledge and practices of Primary Care professionals on diabetic neuropathy: study of social representations.

OBJECTIVES: to analyze the knowledge and practices of Primary Health Care professionals about diabetic neuropathy through their social representations. METHODS: a qualitative, descriptive study, anchored in the procedural aspect of the Theory of Social Representations. It was carried out in four Family Health Units in Belém-Pará, with 31 professionals from four health teams. Data were produced by individual semi-structured interviews, and the corpus was submitted to content analysis. RESULTS: two thematic categories were defined, showing the participants' understanding and imagination about neuropathy, as well as the biopsychosocial repercussions of this complication in patients' daily lives. The multidisciplinary practices developed in the context of disease treatment/prevention and the consequences of this performance were also shown. FINAL CONSIDERATIONS: professionals' representations are anchored in neuropathy occurrence due to the deficient standard of care for themselves by patients, which results in the team's surpassing care attitude as an alternative to illness' challenges.

HIV infection in pregnant women and its challenges for the prenatal care.

OBJECTIVE: To analyze the epidemiological profile of HIV infections in pregnant women. METHODS: Analytical study with a quantitative approach. RESULTS: The HIV rate in pregnant women increased from 1.5/1000 babies born alive, in 2010, to 3.3/1000 in 2017. There was a significant association between the prenatal and the variables educational level (p<0.0001), occupation (p=0.0105), gestational age (p < 0.0001), and type of delivery (p < 0.0001). The mean rate of adherence to the antiretroviral treatment in the prenatal was 68.8% (DP = ± 3.7). CONCLUSION: The high rates of HIV detection in pregnant women suggest the need to intensify the health care to women during the prenatal, guaranteeing an integral care, early diagnoses, and enhancing the strategies to improve the adherence to the antiretroviral treatment, aiming to achieve the viral suppression of the mother by the time of childbirth, thus diminishing the risk of a vertical transmission.

Suicide in indigenous and non-indigenous population: a contribution to health management.

OBJECTIVE: To analyze the sociodemographic and epidemiological profile of suicide in the indigenous and non-indigenous population and the spatiality of the event. METHOD: Epidemiological, descriptive research, carried out with data from the Mortality Information System. Suicide mortality rates were calculated for the 144 municipalities in Pará and linked to the geographic location values of the municipalities; subsequently, thematic maps were built using the QGIS 3.10.3 software. The association between variables was measured by the G test. RESULTS: 1,387 suicide records were studied, and the mortality rate among indigenous people was low in comparison to non-indigenous people, reaching 0.1/100 thousand inhabitants and 17.5/100 thousand inhabitants, respectively. CONCLUSION: Suicide is heterogeneously distributed in the territory, with greater vulnerability of the indigenous people, which demands different policies considering their cultural diversity.

Knowledge of primary health care professionals on health policies for the riverside population.

OBJECTIVES: to analyze the knowledge of health professionals on the health policies for the riverside population; identify how health practices with this group are developed; and discuss facilitators and barriers for the implementation of these policies. METHODS: qualitative and descriptive study with 24 professionals from the Riverside Family Health Strategy Teams in the city of Belém-Pará. Data were collected in individual interviews and analyzed by Content Analysis. RESULTS: although professionals demonstrate knowledge about public health policies, there is a need to expand and strengthen knowledge about health policies for the riverside population. The activities directed to the communities took place in the Unit itself, and some did not occur due to insufficient material and human resources. FINAL CONSIDERATIONS: the greatest barrier for the organization of health care is the lack of material and human resources, and the most prominent facilitator was the union and cohesion of the health team.

Tuberculosis: evaluation of the time between identification of symptoms and beginning of treatment.

OBJECTIVE: To analyze the time elapsed between the identification of respiratory symptoms and the beginning of tuberculosis treatment, considering the sputum smear microscopy and the RMT. METHOD: Descriptive, retrospective epidemiological study, carried out in two Health Units, which were the only units that performed diagnosis by sputum smear microscopy and Rapid Molecular Test in the city. Data on respiratory symptoms with a positive result for tuberculosis were used. Analysis of data distribution and variance was performed, with a significance level of 5%. RESULTS: The longest time interval found was "result/beginning of treatment", for both tests, with a median of 3 days. It was found that the patient takes longer to receive the result when performing the Rapid Molecular Test. CONCLUSION: Patients who had the Rapid Molecular Test waited longer for results when compared to sputum smear microscopy, leading to a reflection on the need for further studies on the operation of health services.

Behaviors related to Quilombola women's health: a social representations study.

OBJECTIVE: To Identify Quilombola women's social representations about health care and to characterize practices performed by them. METHOD: a descriptive, qualitative study, applying the Social Representations Theory, conducted with 30 women from a Quilombola community in the Brazilian Amazon. Individual interviews and thematic content analysis were carried out. RESULTS: Health care practices are related to the home, people, families, and environment, indicating a Quilombola women's extended understanding about health care. In the first instance, natural resources derived from traditional knowledge and use of herbs are applied, in the second instance, the official health system, with the mother-woman being the main caregiver of the family. FINAL CONSIDERATIONS: the mother enables a health care in the family daily life, and she is the main way of access health professionals have to enter the Quilombola community and provide proper care from the official health system to the group.