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Item A contribuição das atividades práticas interdisciplinares no aprendizado de discentes do ensino médio.(2022) Benedito, Atália Júlio; Vita, Margaly Aparecida de Aguiar; Pinto, Elisângela Silva; Vital, Wendel CouraA interdisciplinaridade e a contextualização são orientações contidas nos Parâmetros Curriculares Nacionais a fim de mostrar a inter-relação entre os vários conhecimentos. Entretanto, na maioria das escolas o ensino ainda se revela fragmentado e desconexo da realidade dos seus alunos. Neste sentido, o objetivo deste estudo foi desenvolver e aplicar uma sequência didática interdisciplinar sobre o sistema respiratório evidenciando a interface entre as disciplinas de Biologia e Física. Além disso, foi avaliado, por meio de um questionário aplicado antes e após a intervenção, o conhecimento científico do discente sobre o tema, buscando verificar se houve uma melhora do aprendizado do conteúdo. Foram avaliados 32 estudantes da 2ª série do ensino técnico integrado de uma escola pública da rede federal. A sequência didática foi composta por dez atividades, sendo estas teóricas e práticas. Foi observado que, após a realização da sequência didática, houve um aumento significativo do percentual de acertos nas questões abordadas no questionário. Além disso, verificou-se que, dentre as atividades da sequência didática, a prática foi aquela que os discentes relataram melhor contribuir para a compreensão do conteúdo. Tais resultados mostram a importância de evidenciar a interdisciplinaridade nos conteúdos trabalhados em sala de aula a fim de potencializar o aprendizado e, também, da realização de atividades práticas que aproximem a teoria da vivência cotidiana dos estudantes.Item Resveratrol induces the production of reactive oxygen species, interferes with the cell cycle, and inhibits the cell migration of bladder tumour cells with different TP53 status.(2023) Almeida, Tamires Cunha; Melo, André Sacramento; Lima, Ana Paula Braga; Branquinho, Renata Tupinambá; Silva, Glenda Nicioli daResveratrol is a polyphenolic compound whose antitumor activity has been demonstrated in several types of cancer. However, there are few studies on its molecular mechanisms of action in bladder cancer. Therefore, we aimed to evaluate resveratrol activity in bladder tumour cells with different TP53 gene status. Cytotoxicity, cell proliferation, reactive oxygen species (ROS) production, cell migration, mutagenicity, and CDH1, CTNNBIP1, HAT1, HDAC1, MYC, and SMAD4 gene expression were evaluated. An increase in ROS after resveratrol treatment was accompanied by reduced cell viability and proliferation in all cell lines. In TP53 wild-type cells, the inhibition of cell migration was accompanied by CDH1 and SMAD4 modulation. In TP53 mutated cells, cell migration inhibition with CDH1 and CTNNB1P1 upregulation was observed. In conclusion, resveratrol has antiproliferative effect in bladder tumour cells and its mechanism of action occurred through ROS production, interference with cell cycle, and inhibition of cell migration, independent of TP53 status.Item Avaliação dos serviços de saúde e dos recursos materiais para rastreio do câncer cervical em Ouro Preto - MG.(2022) Oliveira, Renata Rocha e Rezende; Rezende, Giselle Aparecida de Souza; Silva, Bruna Viana; Lage, Ana Luiza; Martins, Bruna Aparecida; Veloso, Marco Antônio; Geöcze, Bruna Albuquerque; Abreu, Ronan David Souza; Rezende, Mariana Trevisan; Carneiro, Cláudia MartinsA realização periódica do exame de Papanicolaou é o método convencional no Brasil para o rastreio do Câncer do Colo do Útero (CCU). As estratégias de serviço e os recursos materiais nas Unidades Básicas de Saúde (UBS) são aspectos fundamentais que refletem na qualidade do programa de rastreamento. Objetivo: Analisar quatro UBS do município de Ouro Preto, Minas Gerais e verificar o contexto local de rastreio do CCU. Métodos: Foi realizado estudo qualitativo, baseado em entrevistas semiestruturadas com enfermeiros e agentes comunitários de saúde (ACS) das UBS selecionadas. Resultados: Observou-se que apenas uma UBS apresentava planta física e recursos materiais adequados à realização do exame. Em geral, as ACS realizavam busca ativa não sistematizada das pacientes para realização do exame de Papanicolau. A conduta para informar os resultados alterados às pacientes era semelhante entre as UBS, porém, não havia padronização para realizar o seguimento dos casos alterados. Além disso, as atividades educativas eram escassas para a comunidade e para a equipe de trabalho. Conclusão: Percebe-se que uma estrutura física de qualidade associada a uma equipe de saúde da família (ESF) treinada favorece o estabelecimento de programas de rastreio exitosos. Por não se tratar de uma realidade de todas as UBS locais, é necessário lançar princípios de organização para sistematizar as estratégias de busca ativa, registro e acompanhamento das pacientes, sendo os ACS fundamentais neste processo, devido à proximidade com a população.Item Emotionally subjective reactivity to cervical cytology pictures is modulated by expertise.(2022) Oliveira, Jacqueline Alfenas de; Souza, Miriam de Cássia; Cunha, Laila Fernandes da; Mota, Bruna Eugênia Ferreira; Rezende, Mariana Trevisan; Carneiro, Cláudia Martins; Pereira, Mirtes Garcia; Mocaiber, Izabela; Souza, Gabriela Guerra Leal deOur aims were to create a catalog of cytological pictures and to evaluate the valence (level of pleasantness/ unpleasantness) and arousal (level of calm/excitement) of these pictures in individuals with different occupations. The sample consisted of medical and law college students and cytopathologists. Valence and arousal score for general pictures were not modulated by expertise in cytology. However, students judged the cytological pictures to be lower in valence and in arousal than the cytopathologists. The cytopathologists classified cytological pictures with lesions as lower in valence and higher in arousal than cytological pictures without lesions.Item The orphan G protein-coupled receptor, GPR139, is expressed in the hypothalamus and is involved in the regulation of body mass, blood glucose, and insulin.(2023) Nogueira, Pedro Augusto Silva; Assis, Alexandre Moura; Zanesco, Ariane Maria; Bombassaro, Bruna; Ferraz, Ana Luísa Gallo; Simões, Marcela Rodrigues; Engel, Daiane Fátima; Razolli, Daniela Soares; Gaspar, Joana Margarida Navalho; Donato Junior, José; Velloso, Licio AugustoGPR139 is an orphan G-protein-coupled receptor that is expressed in restricted areas of the nervous system, including the hypothalamus. In this study, we hypothesized that GPR139 could be involved in the regulation of energy balance and metabolism. In the first part of the study, we confirmed that GPR139 is expressed in the hypothalamus and particularly in proopiomelanocortin and agouti-related peptide neurons of the mediobasal hypothalamus. Using a lentivirus with a short-hairpin RNA, we inhibited the expression of GPR139 bilaterally in the mediobasal hypothalamus of mice. The intervention promoted a 40% reduction in the hypothalamic expression of GPR139, which was accompanied by an increase in body mass, a reduction in fasting blood glucose levels, and an increase in insulin levels. In the hypothalamus, inhibition of GPR139 was accompanied by a reduction in the expression of orexin. As previous studies using a pharmacological antagonist of orexin showed a beneficial impact on type 2 diabetes and glucose metabolism, we propose that the inhibition of hypothalamic GPR139 could be acting indirectly through the orexin system to control systemic glucose and insulin. In conclusion, this study advances the characterization of GPR139 in the hypothalamus, demonstrating its involvement in the regulation of body mass, blood insulin, and glycemia.Item Serum biomarkers in patients with unilateral or bilateral active pulmonary tuberculosis : immunological networks and promising diagnostic applications.(2023) Pascoal, Vanessa Peruhype Magalhães; Araújo, Fernanda Fortes de; Papini, Tatiane Figueiredo de Morais; Wendling, Ana Paula Barbosa; Azevedo, Ana Carolina Campi; Reis, Jordana Grazziela Alves Coelho dos; Almeida, Isabela Neves de; Antonnelli, Lis Ribeiro do Valle; Amaral, Laurence Rodrigues do; Gomes, Matheus de Souza; Sousa, Joaquim Pedro Brito de; Santos, Silvana Maria Elói; Augusto, Valéria Maria; Dalcolmo, Margareth Maria Pretti; Carneiro, Cláudia Martins; Carvalho, Andréa Teixeira de; Martins Filho, Olindo AssisThe present observational study was designed to characterize the integrative profile of serum soluble mediators to describe the immunological networks associated with clinical findings and identify putative biomarkers for diagnosis and prognosis of active tuberculosis. The study population comprises 163 volunteers, including 84 patients with active pulmonary tuberculosis/(TB), and 79 controls/(C). Soluble mediators were measured by multiplexed assay. Data analysis demonstrated that the levels of CCL3, CCL5, CXCL10, IL-1β, IL-6, IFN-γ, IL-1Ra, IL-4, IL-10, PDGF, VEGF, G-CSF, IL-7 were increased in TB as compared to C. Patients with bilateral pulmonary involvement/(TB-BI) exhibited higher levels of CXCL8, IL-6 and TNF with distinct biomarker signatures (CCL11, CCL2, TNF and IL-10) as compared to patients with unilateral infiltrates/(TB-UNI). Analysis of biomarker networks based in correlation power graph demonstrated small number of strong connections in TB and TB-BI. The search for biomarkers with relevant implications to understand the pathogenetic mechanisms and useful as complementary diagnosis tool of active TB pointed out the excellent performance of single analysis of IL-6 or CXCL10 and the stepwise combination of IL-6 → CXCL10 (Accuracy = 84 %; 80 % and 88 %, respectively). Together, our finding demonstrated that immunological networks of serum soluble biomarkers in TB patients differ according to the unilateral or bilateral pulmonary involvement and may have relevant implications to understand the pathogenetic mechanisms involved in the clinical outcome of Mtb infection.Item Long non-coding rna and chemoresistance in bladder cancer – a mini review.(2022) Lima, Ana Paula Braga; Silva, Glenda Nicioli daBladder cancer is the 10th most common cancer worldwide. It is a heterogeneous disease, comprising several tumor subtypes with differences in histology, genomic aberrations, prognosis and sensitivity to anti-cancer treatments. Although the treatment of bladder cancer is based tumor classifications and gradings, patients have different clinical response. In recent years, long non-coding RNAs (lncRNAs) were associated with bladder cancer chemoresistance. Thus, lncRNAs seem to be promising targets in treatment of bladder cancer. This review highlights the recent findings concerning lncRNAs and their relevance to the chemoresistance of bladder cancer. This may provide a basis for exploiting more robust therapeutic approaches in the future.Item Examining the mental health of the academic community at an institution for higher education during the COVID-19 pandemic.(2022) Paula, Waléria de; Khouri, Isadora Dantas Sakr; Machado, Elaine Leandro; Silva, Glenda Nicioli da; Roever, Leonardo; Meireles, Adriana LúciaDue to the COVID-19 pandemic, the Higher Education Institutions had to suspend their on-site activities and adapt to the new scenario. Therefore, the objective of the research was to investigate the effects of the COVID-19 pandemic on the mental health of the academic community of a Brazilian public university. This is a crosssectional study, at a Brazilian public university, that used the baseline data from a longitudinal study carried out with employees and students. Participants answered a self-administered and confidential questionnaire in online platform, composed of sociodemographic, economic, lifestyles and mental health issues. 1,353 students and 372 employees participated. The prevalence of anxiety disorder symptoms among students and employees was 46.12% and 17.47%, depression 54.62% and 22.85% and stress 47.45% and 22.58%, respectively. The co-occurrence of symptoms was 33.56% among university students and 10.75% among employees. Falling family income, having stopped smoking and negative self-rated health, during the COVID-19 pandemic, may be the reasons for the high prevalence of co-occurrence of anxiety, depression and stress disorders among the academic community.Item Modulation of non-coding RNAs by natural compounds as a potential therapeutical approach in oral cancer : a comprehensive review.(2022) Almeida, Tamires Cunha; Pereira, Isadora Oliveira Ansaloni; Oliveira, Edymara dos Anjos; Souza, Daniel Vitor de; Ribeiro, Daniel Araki; Silva, Glenda Nicioli daOral cancer is a disease with high incidence and mortality worldwide, and its treatment still needs to be improved. The search for new therapies using natural products is strongly supported, given the wide chemical range of these compounds. In addition, phytochemicals can exert antitumor activities by several mechanisms of action, including the modulation of non-coding RNAs. Thus, in this review, we discussed the role of non-coding RNAs, including circular RNAs, microRNAs, and long non-coding RNAs, in oral cancer and presented their potential as treatment targets using natural products. Some natural products capable of being used to treat oral cancer have been suggested.Item Chrysin inhibits the cell viability, induces apoptosis and modulates expression of genes related to epigenetic events in bladder cancer cells.(2022) Lima, Ana Paula Braga; Melo, André Sacramento; Ferreira, Gabriel Monteze; Silva, Glenda Nicioli daThis study was conducted with the aim of exploring the molecular and cellular mechanisms of action of the chrysin (natural flavonoid compound) on bladder tumour cell lines with different status of TP53 (RT4, 5637 and T24). The cells were treated with different concentrations of chrysin (20, 40, 60, 80 and 100 mM) to analyze the cell viability, nuclear division index, mutagenicity, apoptosis rates and expression of genes related to epigenetic events (DNMT1, HAT1 and HDAC1). Results showed that the treatment with chrysin reduced the cell viability and caused apoptosis, regardless TP53. Moreover, in the TP53-mutated cell lines, chrysin modulated the expression of the DNMT1, HAT1 and HDAC1 epigenetic genes, which might be a plus to the death observed in the cells with p53 mutation.Item Molecular characterization of nontuberculous Mycobacteria in a tuberculosis and HIV reference unit in the State of Amazonas, Brazil.(2022) Lima, Ana Carolina de Oliveira de; Schmid, Karen Barros; Melo, Hilda Ferreira de; Athayde, Rafaella Christine; Monte, Rossiclea Lins; Almeida, Isabela Neves de; Miranda, Silvana Spíndola de; Kritski, Afrânio; Rossetti, Maria Lucia Rosa; Santos, Marcelo Cordeiro dosBackground: In recent years, the prevalence of nontuberculous mycobacterial (NTM) infections has increased in different regions of the world. The American Thoracic Society (ATS) recommends standardized identification criteria, reinforcing the need for faster and less complicated clinical and laboratory techniques. Methods: In this retrospective study, NTM species isolated from pulmonary, extrapulmonary, and disseminated samples from patients treated at a TB/HIV reference unit in the State of Amazonas from 2011 to 2014 were identified through a combination of molecular techniques. Results: To identify the molecular technique, 50 cryopreserved NTM cultures were recovered and subcultivated in culture medium. The potentially pathogenic NTM species identified were M. avium, M. intracellulare, M. kansasii, M. chelonae, M. abscessus, M. fortuitum, and M. peregrinum. Results of GenoType® showed moderate agreement with those of genomic sequencing (kappa = 0.60), whereas the results obtained by the PRA-hsp65 technique disagreed with the results obtained by sequencing (kappa = 0.49). Conclusions: Our findings highlight that GenoType CM is a good method for the identification of NTM, as well as the need for the application of standardized criteria, such as those set forth by the ATS.Item Impact of a computer system as a triage tool in the management of pulmonary tuberculosis in a HIV reference center in Brazil.(2022) Libório, Mariana Pitombeira; Kritski, Afrânio; Almeida, Isabela Neves de; Miranda, Pryscila Fernandes Campino; Mesquita, Jacó Ricarte Lima de; Mota, Rosa Maria Salani; Sousa, George Jó Bezerra; Neto, Roberto da Justa Pires; Leitão, Terezinha do Menino Jesus SilvaBackground: The Neural Clinical Score for tuberculosis (NCS-TB) is a computer system developed to improve the triage of presumed pulmonary TB (pPTB). Methods: A study was performed with cohorts of pPTB patients cared for at a reference hospital in Northeast Brazil. Results: The NCS-TB sensitivity was 76.5% for TB diagnosis, which shortened the time from triage to smear microscopy results (3.3 to 2.5 days; p<0.001) and therapy initiation (6.7 to 4.1 days; p=0.045). Conclusions: Although the NCS-TB was not suitable as a screening tool, it was able to optimize laboratory diagnosis and shorten the time to treatment initiation.Item LncRNA JHDM1D-AS1 Is a key biomarker for progression and modulation of gemcitabine sensitivity in bladder cancer cells.(2023) Pereira, Isadora Oliveira Ansaloni; Silva, Glenda Nicioli da; Almeida, Tamires Cunha; Lima, Ana Paula Braga; Sávio, André Luiz Ventura; Leite, Katia Ramos Moreira; Salvadori, Daisy Maria FáveroLong non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.Item Uric acid level in climacteric women and its association with clinical and metabolic parameters.(2023) Souza, Laura Alves Cota e; D’Angelo, Georgia Carvalho de Oliveira; Silva, Glenda Nicioli da; Lima, Angélica AlvesClimacteric women often experience unfavorable metabolic changes. Consequently, identifying markers that may contribute to such undesirable changes is imperative. This study aimed to evaluate serum uric acid (UA) concentration and its association with metabolic and clinical parameters in climacteric women. We selected 672 women between 40 and 65 years and performed interviews, biochemical analyses, blood pressure, and anthropometric measurements. UA levels were determined using the enzymatic-colorimetric method. We compared variables according to the quartiles of UA using the Kruskal–Wallis test. The mean UA level was 4.9 ± 1.5 mg/dl, ranging from 2.0 to 11.6 mg/dl. We found that UA levels greater than 4.8 mg/dl were associated with adverse metabolic parameters in climacteric women. For all anthropometric and biochemical variables, we observed signifcantly better results in women who had lower UA levels (p< 0.05). Similarly, we observed a signifcant increase in blood pressure, frequency of metabolic syndrome, and cardiovascular risk as UA levels increased (p< 0.05). Our fndings showed that climacteric women with high levels of UA were more likely to have adverse metabolic and clinical parameters than those with lower UA levels. Further studies may determine the causal relationship between UA and metabolic changes in climacteric women.Item Hypothalamic CREB regulates the expression of Pomc-processing enzyme Pcsk2.(2022) Zanesco, Ariane Maria; Mendes, Natália Ferreira; Engel, Daiane Fátima; Gaspar, Rodrigo Stellzer; Oliveira, Davi Sidarta; Donato Junior, José; Velloso, Licio AugustoBackground: The hypothalamic proopiomelanocortin (Pomc) neurons act as first-order sensors of systemic energy stores, providing signals that regulate caloric intake and energy expenditure. In experimental obesity, dietary saturated fatty acids affect Pomc endopeptidases (PCs), resulting in the abnormal production of the neurotransmitters α-melanocyte-stimulating hormone (α-MSH) and β-endorphin, thus impacting energy balance. The cAMP response element-binding protein (CREB) is one of the transcription factors that control the expression of Pomc endopeptidases; however, it was previously unknown if dietary fats could affect CREB and consequently the expression of Pomc endopeptidases. Methods: Here, we used single-cell RNA sequencing analysis, PCR, immunoblot, ELISA and immunofluorescence histological assays to determine the impact of a high-fat diet (HFD) on the expression and function of hypothalamic CREB and its impact on the melanocortinergic system. Results: The results indicate that CREB is expressed in arcuate nucleus Pomc neurons and is activated as early as nine hours after the introduction of a high-fat diet. The inhibition of hypothalamic CREB using a short-hairpin RNA lentiviral vector resulted in increased diet-induced body-mass gain and reduced energy expenditure. This was accompanied by reduced expression of the Pomc endopeptidases, protein convertase 2, which are encoded by Pcsk2, and by the loss of the high-fat-diet-induced effect to inhibit the production of α-MSH. Conclusions: This study provides the first evidence for the involvement of CREB in the abnormal regulation of the hypothalamic Pomc endopeptidase system in experimental obesity.Item Defining the early stages of intestinal colonisation by whipworms.(2022) Correa, Maria Adelaida Duque; Goulding, David; Rodgers, Faye H.; Gillis, J. Andrew; Cormie, Claire; Rawlinson, Kate A.; Bancroft, Allison J.; Bennett, Hayley M.; Lotkowska, Magda E.; Reid, Adam J.; Speak, Anneliese O.; Scott, Paul; Redshaw, Nicholas; Tolley, Charlotte; McCarthy, Catherine; Brandt, Cordelia; Sharpe, Catherine; Ridley, Caroline; Moya, Judit Gali; Carneiro, Cláudia Martins; Starborg, Tobias; Hayes, Kelly S.; Holroyd, Nancy; Sanders, Mandy; Thornton, David J.; Grencis, Richard K.; Berriman, MatthewWhipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche.Item Recent HPV self-sampling use for cervical cancer screening in Latin America and Caribbean : a systematic review.(2022) Dartibale, Camila Buziquia; Prado, Gabriela de Castro; Carobeli, Lucimara Rodrigues; Meirelles, Lyvia Eloiza de Freitas; Damke, Gabrielle Marconi Zago Ferreira; Damke, Edilson; Morelli, Fabrício; Souza, Raquel P.; Group PREVENT YOURSELF; Silva, Vânia R. S. da; Consolaro, Márcia Edilaine LopesObjective: Cervical cancer is one of the deadliest cancers among women in Latin America and Caribbean (LAC), where most of the countries have not been successful in implementing population-level cytology-based screening programs. An increasing body of evidence supports the validity of selfsampling as an alternative to clinician collection for primary Human papillomavirus (HPV) screening. Therefore, this work aims to summarize recent HPV self-sampling approaches in LAC. Method: We performed a systematic review to identify studies focused on “Self-sampling”, and “Human Papillomavirus DNA test” and “Latin America” in PubMed, Embase, Web of Science, Cochrane library and SCOPUS databases for publications dating between 01 January 2017 and 15 March 2022 based on the Preferred Reporting Items for systematic reviews and meta-analysis (PRISMA) statement. Additionally, the references of the articles were carefully reviewed. Results: Of the 97 records selected, 20 studies including 163,787 participants, with sample sizes for individual studies ranging from 24 to 147,590 were included in this review. Studies were conducted in 10 LAC countries (18.5%), most with upper medium-income economies (70%). The range of age was 18 to ≥65 years. The vast majority of the studies (85%) addressed the HPV selfsampling strategy for primary cervical cancer screening with overall success for all women including under/never screened and those from special populations (rural, indigenous and gender minorities). Women generally found HPV selfsampling highly acceptable regardless of age, setting of collection, target population or country of residence. Conclusions: HPV self-sampling is a promising strategy to overcome the multiple barriers to cervical cancer screening in LAC settings and increasing attendance in underscreened women in countries/territories with wellestablished screening programs. Furthermore, this strategy is useful even in LAC countries/territories without organized cervical cancer screening and in special populations such as indigenous, rural and transgender women. Therefore, the information generated by the recent initiatives for HPV selfsampling approach in LAC can be beneficial for decision-making in both new and existing programs in the region.Item Pharmacometrics : the already‑present future of precision pharmacology.(2022) Bandeira, Lorena Cera; Pinto, Leonardo; Carneiro, Cláudia MartinsThe use of mathematical modeling to represent, analyze, make predictions or providing information on data obtained in drug research and development has made pharmacometrics an area of great prominence and importance. The main purpose of pharmacometrics is to provide information relevant to the search for efcacy and safety improvements in pharmacotherapy. Regulatory agencies have adopted pharmacometrics analysis to justify their regulatory decisions, making those decisions more efcient. Demand for specialists trained in the feld is therefore growing. In this review, we describe the meaning, history, and development of pharmacometrics, analyzing the challenges faced in the training of professionals. Examples of applications in current use, perspectives for the future, and the importance of pharmacometrics for the development and growth of precision pharmacology are also presented.Item Influência da suplementação com as vitaminas B9 (ácido fólico) e B12 (cobalamina) no tratamento de pacientes com antidepressivos : uma revisão narrativa.(2022) Sousa, Lucas José de Resende; Paula, Carmen Aparecida de; Almeida, Martha Elisa Ferreira deNo Brasil, cerca de 5,8% da população possui o diagnóstico de depressão, e apenas 1/3 destes pacientes estão em tratamento, devido os efeitos adversos dos medicamentos antidepressivos que têm impulsionado novas estratégias terapêuticas. Em tais pacientes têm sido observadas altas concentrações de homocisteína, um aminoácido com propriedades neurodegenerativas. Desta forma opções terapêuticas que proporcionam a manutenção dos níveis séricos de homocisteína dentro dos valores de referência estão se tornando alvos para o tratamento da depressão de forma isolada ou em associação com os antidepressivos habituais. Esta revisão narrativa tem como objetivo avaliar a influência da suplementação com as vitaminas B9 (ácido fólico) e B12 (cobalamina) no tratamento de pacientes com antidepressivos. Identificou-se que estas vitaminas são nutrientes importantes para a síntese de neurotransmissores, bem como a redução dos níveis de homocisteína no cérebro. Os pacientes com depressão, e em tratamento ou não com antidepressivos, obtiveram uma melhora significativa do seu quadro clínico quando receberam o suplementado destes dois micronutrientes, pois eles potencializaram os efeitos dos antidepressivos, e diminuíram os níveis de homocisteína na circulação sanguínea e a gravidade dos sintomas depressivos, principalmente naqueles pacientes portadores de altas concentrações de homocisteína plasmática. Concluiu-se que o baixo custo para aquisição das vitaminas B9 e B12 é um fator importante, e tem despertando a possibilidade da sua inclusão nas diretrizes de tratamento para a depressão no sentido de melhorar a eficiência dos medicamentos e diminuir a gravidade dos sintomas.Item Correlation of serum anti‑Mullerian hormone with hormonal and environmental parameters in Brazilian climacteric women.(2023) Gouvea, Thiago Magalhães; Souza, Laura Alves Cota e; Lima, Angélica AlvesThis study aimed to identify the correlation among anti-Mullerian Hormone serum levels and 25-OHD, obesity, metabolic syndrome (MetS), and sexual hormones in climacteric women classifed according to stages of reproductive aging (SRA). A cross-sectional study was conducted with a total of 177 Brazilian climacteric women between 40 and 64 years old. Concentrations of AMH were measured using the Access 2 Immunoassay System. A multiple linear regression analysis was used to identify the relationship among AMH, 25-OH-D, obesity, MetS, sexual hormones, sociodemographic and lifestyle factors. AMH levels decreased with increased age (B= − 0.059; p< 0.001), and reproductive aging (B= − 0.483; p< 0.001). Obesity indicators, lifestyle characters, 25-OH-D levels and MetS were not signifcantly associated with AMH serum concentration. Negative correlation was found for FSH (B= − 0.009; p< 0.001) and LH (B= − 0.006; p= 0.004); positive correlation for E2 (B= 0.001; p= 0.011), DHEAS (B= 0.003; p< 0.001) and SHBG (B= 0.003; p= 0.005). In the model adjusted for SRA, FSH levels (p< 0.001) and DHEAS (p= 0.014) were associated with AMH. Although, with the adjustment for age, only FSH remained with a signifcant association (p= 0.001). Of the other analytes, none was associated with AMH, regardless of the model ft. Our fndings confrm that serum AMH level decreased with age and FSH levels, but there is no correlation between AMH with obesity, 25-OH-D, MetS or other sexual hormones in Brazilian climacteric women.