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Marina A Costa,1 Layane M Teodoro,1 Gustavo H Bahia-de-Oliveira,2 Ana Paula N Nunes,3 Ricardo A Barata1 1Laboratório de Parasitologia, Departamento de Ciências Biológicas, Universidade Federal dos Vales dos Jequitinhonha e Mucuri, Diamantina, MG, Brazil; 2Laboratório de Doenças Parasitárias, Departamento de Farmácia, Universidade Federal dos Vales dos Jequitinhonha e Mucuri, Diamantina, MG, Brazil; 3Laboratório de Bioestatística e Epidemiologia, Departamento de Ciências Básicas, Universidade Federal dos Vales dos Jequitinhonha e Mucuri, Diamantina, MG, Brazil Background: Banknotes are objects of great turnover and diffusion among the population, and can be efficient mechanisms in the dissemination of several intestinal parasites. This study investigated the presence of biological forms of intestinal parasites present in circulating cash banknotes in the city of Diamantina, Minas Gerais, Brazil, aiming to propose interventions aimed at improving local public health. Materials and methods: Between February and April 2017, samples of banknotes collected in five commercial establishments of the city were analyzed, namely: 1) gas station, 2) supermarket, 3) butchery, 4) pharmacy and 5) free fair. Ten circulating banknotes of each value (R$2.00, R$5.00, R$10.00, R$20.00, R$50.00 and R$100.00) were exchanged for new banknotes, washed with Tween 80 and, after spontaneous sedimentation, analyzed under an optical microscope with a magnification of 10× and 40×. Results: Cysts of Entamoeba coli (74.60%), cysts of Endolimax nana (16.94%), Giardia lamblia cysts (4.44%), unidentified nematode larvae (2.02%), Hymenolepis sp. (0.81%), Taenia sp. (0.81%) and Ancylostomidae larvae (0.40%) were found. Conclusions: The results revealed the need for improvements in basic sanitation, health and education activities that emphasized the importance of proper hand hygiene. Keywords: intestinal parasites, banknotes, Diamantina

Introduction: The use of natural products for therapeutic purposes is a common practice throughout the world, in part, due to the global obesity epidemic and the search for products with appetite suppression and weight loss properties, which include nutritional supplements, vitamins and minerals to herbal products. It is known that such products may be associated with various adverse health effects. Thus, the objective of this study is to report a series of cases of patients, who presented fulminant liver failure (HFI) requiring liver transplantation (LT), related to the consumption of products used for weight loss., Material and Methods: This is a retrospective cohort based on the evaluation of patients listed for LT due to IHF at the Hospital das Clínicas of the Universidade Estadual de Campinas, between 1991 and 2022, with patients who had confirmed consumption of products with the aim of loss being selected., Results: During the studied period, 92 patients were listed for HT due to IHF according to the Kings College criteria, with 5 cases being selected with proven consumption of herbal products for weight loss, and other causes that could explain the IHF were excluded. Four (80%) of the patients were female, with a mean age of 40.5 years, and 40% of the cases died., Discussion and Conclusions: Unlike traditional pharmaceutical medicines, in most countries, the commercialization of these products is not conditioned on clinical and safety evidence or prior approval by regulatory bodies. Hepatoxicity can be related to several factors, such as the presence of toxins naturally found in plants, the presence of heavy metals, contamination during obtaining or processing and the addition of substances omitted from the labels. The use of weight loss products can evolve with IHF, a fact that deserves attention, due to ease of access and growing demand, and it is important to regulate the trade of these products and raise public awareness about the risks of use without professional supervision and guidance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This ecological study examined time series, from 2002 to 20121, of age-adjusted coefficients of cervical cancer mortality, in Brazil, in women aged 20 years or more, by race. The information sources were Brazil's mortality information system (Sistema de Informação sobre Mortalidade - SIM) and the official bureau of statistics (Instituto Brasileiro de Geografia e Estatística - IBGE). Annual changes in age-adjusted mortality rates were calculated using the Prais-Winsten linear regression method. Black women die more and the rate is decreasing less. Racial inequality has increased over the years. In 2002, there were 0.08 more deaths per 100,000 women in the black population than among white women; in 2021, the number was one death. Health policymaking should consider racial differences in the implementation of strategies and goals.

Water scarcity is one of the main abiotic factors that limit agricultural production. In this sense, the identification of genotypes tolerant to water deficit associated with irrigation management strategies is extremely important. In this context, the objective of this study was to evaluate the morphology, production, water consumption, and water use efficiency of colored fiber cotton genotypes submitted to irrigation strategies with a water deficit in the phenological phases. Two experiments were conducted in succession. In the first experiment, a randomized block design was used in a 3 × 7 factorial scheme, corresponding to three colored cotton genotypes (BRS Rubi, BRS Jade, and BRS Safira) in seven irrigation management strategies with 40% of the real evapotranspiration (ETr) varying the phenological stages. In the second experiment, the same design was used in a 3 × 10 factorial arrangement (genotypes × irrigation management strategies). The water deficit in the vegetative phase can be used in the first year of cotton cultivation. Among the genotypes, 'BRS Jade' is the most tolerant to water deficit in terms of phytomass accumulation and fiber production.

Understanding the ecological role of species with overlapping distributions is central to inform ecosystem management. Here we describe the diet, trophic level and habitat use of three sympatric stingrays, Hypanus guttatus, H. marianae and H. berthalutzae, through combined stomach content and stable isotope (δ 13 C and δ 15 N) analyses. Our integrated approach revealed that H. guttatus is a mesopredator that feeds on a diverse diet of benthic and epibenthic marine and estuarine organisms, principally bivalve molluscs, Alpheus shrimp and teleost fishes. Isotopic data supported movement of this species between marine and estuarine environments. H. berthalutzae is also a marine generalist feeder, but feeds primarily on teleost fishes and cephalopods, and consequently occupies a higher trophic level. In contrast, H. marianae is a mesopredator specialized on shrimps and polychaetas occurring only in the marine environment and occupying a low niche breadth. While niche overlap occurred, the three stingrays utilized the same prey resources at different rates and occupied distinct trophic niches, potentially limiting competition for resources and promoting coexistence. These combined data demonstrate that these three mesopredators perform different ecological roles in the ecosystems they occupy, limiting functional redundancy., (© 2022 Fisheries Society of the British Isles.)

Institutional racism is prevalent in the health services in Brazil and is based on concrete power relations that subjugate, dominate and exclude blacks from having adequate access to health care and health institutions. This critical essay analyzes the importance of expanding the debate, and the production of knowledge about the health of the black population (HBP), focusing on two points: the role of the National Policy for the Integral Health of the Black Population (PNSIPN) and the importance of including the skin color item in the health information systems; and the need for a process of permanent training of professionals, including contents related to the understanding of racism as an element of the social determination of health/disease and heir effects. To demonstrate how structural and institutional racism have affected the black population, we bring also examples of the quilombola populations in the context of the Covid-19 pandemic in the country since 2020. It is concluded that the promotion of care, the reduction of inequities and the quality of health care need to undergo changes in several dimensions, such as the strengthening of the SUS, the daily fight against structural and institutional racism, among others.

Introduction and Hypothesis: Mayer-Rokitansky-Küster-Hauser syndrome affects about 1 in 5000 live female births and is associated with gonadal dysgenesis and primary amenorrhea. Neovaginoplasty has been established as an appropriate treatment option for patients who have failed or denied dilation therapy. In search of accessible, economical material with low risk of complications, the team proposed the use of Nile tilapia fish skin (NTFS) as an innovative biomaterial in the neovaginoplasty procedure for vaginal agenesis management. NTFS has noninfectious microbiota, morphologic structure comparable to human skin and high in vivo bioresorption., Methods: In this descriptive study, the method offered an anatomical and functional neovagina to 11 patients efficiently, quickly and safely. Correct post-surgical dilation is still extremely important to keep the neovagina's size > 6 cm., Results: Histological and immunohistochemical analysis demonstrated the formation of a stratified squamous epithelium with strong marking for cytokeratins, FGF and EGFR, similar to healthy adult vaginal tissue., Conclusions: Since NTFS is a low cost and easily accessible biomaterial, this technique proves to be an inexpensive therapeutic possibility for the health system with excellent advantages for patients., (© 2022. The International Urogynecological Association.)

Maternal separation (MS) is a risk factor for major depressive disorder. Both cancer and depression seem to share a common biological link. Here, we evaluated the progression of melanoma and the underlying mechanisms related to this progression, namely cell proliferation and apoptosis, in adult female mice exposed to MS. Female C57BL/6 mice were exposed to MS for 60 min/day during the first 2 postnatal weeks (here called MS mice) or left undisturbed (here called non-MS mice). Melanoma cells were inoculated subcutaneously into the axillary region of adult animals, and tumor progression was evaluated for 25 days. Adult MS mice presented depressive-like behavior and working memory deficits. MS accelerated murine melanoma growth by mechanisms related to decreased apoptosis and increased cell proliferation rate, such as increased expression of IL-6 and mTOR. MS stimulated eukaryotic elongation factor 2 expression and increased the number of circulating monocytes and DNA damage in peripheral blood leukocytes, an effect associated with oxidative DNA damage. In conclusion, MS accelerated the progression of murine melanoma by mechanisms related to tumor proliferation and apoptosis, revealing a relationship between adverse childhood experiences and cancer progression, particularly melanoma., (© 2021 New York Academy of Sciences.)

This study aimed to examine the factors associated with body dissatisfaction in adolescents. This is a cross-sectional study with students from two public and four private schools in the metropolitan region of Rio de Janeiro. Body dissatisfaction was evaluated using the Body Silhouette Scale, by the difference between the image they perceive as their current image and the one they would like to have. The association was assessed by hierarchical logistic regression multinomial model, by estimating odds ratios (OR) and 95% confidence intervals (95%CI). Among the 1,019 adolescents evaluated (13-19 years), 75% showed body dissatisfaction, 41.4% wishing for a smaller silhouette and 33.7% wishing for larger silhouettes. The wish for a smaller silhouette was more significant in girls, overweight adolescents, those with an unsatisfactory meal pattern, and with higher waist circumference. Adolescents that had been exposed to teasing due to their body shape increased the probability of wishing for both smaller and larger silhouettes. Strategies are required for a more positive perception of body image, especially for girls and for overweight adolescents, which provide guidance on adequate meal consumption and prevent exposure to peer teasing, valuing coexistence and well-being in the face of existing bodily differences.

Recent data indicate that IGF1R/IRS signaling is a potential therapeutic target in BCR-ABL1-negative myeloproliferative neoplasms (MPN); in this pathway, IRS2 is involved in the malignant transformation induced by JAK2 V617F , and upregulation of IGF1R signaling induces the MPN phenotype. NT157, a synthetic compound designed as an IGF1R-IRS1/2 inhibitor, has been shown to induce antineoplastic effects in solid tumors. Herein, we aimed to characterize the molecular and cellular effects of NT157 in JAK2 V617F -positive MPN cell lines (HEL and SET2) and primary patient hematopoietic cells. In JAK2 V617F cell lines, NT157 decreased cell viability, clonogenicity, and cell proliferation, resulting in increases in apoptosis and cell cycle arrest in the G 2 /M phase (p < 0.05). NT157 treatment inhibited IRS1/2, JAK2/STAT, and NFκB signaling, and it activated the AP-1 complex, downregulated four oncogenes (CCND1, MYB, WT1, and NFKB1), and upregulated three apoptotic-related genes (CDKN1A, FOS, and JUN) (p < 0.05). NT157 induced genotoxic stress in a JAK2/STAT-independent manner. NT157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients (p < 0.05). These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN.

The IGF1R/IRS1 signaling is activated in acute lymphoblastic leukemia (ALL) and can be targeted by the pharmacological inhibitors NT157 (IGF1R-IRS1/2 inhibitor) and OSI-906 (IGF1R/IR inhibitor). Here we investigate the cellular and molecular effects of NT157 and OSI-906 in ALL cells. NT157 and OSI-906 treatment reduced viability, proliferation and cell cycle progression in ALL cell lines. Similarly, in primary samples of patients with ALL, both OSI-906 and NT157 reduced viability, but only NT157 induced apoptosis. NT157 and OSI-906 did not show cytotoxicity in primary samples from healthy donor. NT157 and OSI-906 significantly decreased Jurkat cell migration, but did not modulate Namalwa migration. Consistent with the more potent effect of NT157 on cells, NT157 significantly modulated expression of 25 genes related to the MAPK signaling pathway in Jurkat cells, including oncogenes and tumor suppressor genes. Both compounds inhibited mTOR and p70S6K activity, but only NT157 inhibited AKT and 4-EBP1 activation. In summary, in ALL cells, NT157 has cytotoxic activity, whereas OSI-906 is cytostatic. NT157 has a stronger effect on ALL cells, and thus the direct inhibition of IRS1 may be a potential therapeutic target in ALL., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.

The recurrent gain-of-function JAK2 V617F mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we investigate and compare effects of metformin and ruxolitinib alone and in combination on cell signaling and cellular functions in JAK2 V617F -positive cells. In JAK2 V617F -expressing cell lines, metformin treatment significantly reduced cell viability, cell proliferation, clonogenicity, and cellular oxygen consumption and delayed cell cycle progression. Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin plus ruxolitinib demonstrated more intense reduction of cell viability and induction of apoptosis compared to monotherapy. Notably, metformin reduced Ba/F3 JAK2 V617F tumor burden and splenomegaly in Jak2 V617F knock-in-induced MPN mice and spontaneous erythroid colony formation in primary cells from polycythemia vera patients. In conclusion, metformin exerts multitarget antileukemia activity in MPN: downregulation of JAK2/STAT signaling and mitochondrial activity. Our exploratory study establishes novel molecular mechanisms of metformin and ruxolitinib action and provides insights for development of alternative/complementary therapeutic strategies for MPN.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by abnormal proliferation and accumulation of lymphoblasts in the hematopoietic system. Stathmin 1 is a proliferation marker for normal lymphocytes, which has been described as highly expressed in ALL patients and functionally important for leukemia phenotype. In the present study, we expand our previous observations and aim to investigate Stathmin 1 expression and its impact on laboratory features and clinical outcomes in an independent cohort of ALL patients, and to verify the effects of paclitaxel treatment on Stathmin 1 phosphorylation and cell viability in ALL cell lines. In ALL patients, Stathmin 1 expression was significantly increased, associated with lower age onset and positively correlated with white blood cell counts, but did not impact on clinical outcomes. Functional assays revealed that paclitaxel induces Stathmin 1 phosphorylation at serine 16 (an inhibitory site), microtubule stability and apoptosis in Jurkat and Namalwa cell lines. Paclitaxel treatment did not modulate cell viability of normal peripheral blood leukocytes. In conclusion, our data confirm increased levels of Stathmin 1 in ALL patients and that therapeutic doses of paclitaxel inhibits Stathmin 1 function and promote microtubule stability and apoptosis in ALL cells.

Insulin-like growth factor 1 (IGF1) and its receptor IGF1R regulate normal cell growth and contribute to cell transformation through activation of downstream signaling pathways. In fibroblast cells, insulin receptor substrate 1 (IRS1), through IGF1 signaling, was found to be the key protein for nuclear translocation of β-catenin and MYC transcription activation. We herein investigated the IRS1/β-catenin axis in acute lymphoblastic leukemia (ALL) cells. Samples were obtained from 45 patients with ALL and 13 healthy donors. ALL cell lines were used. Gene expression was measured by quantitative PCR. Protein expression, associations, and cellular localization were evaluated by immunoprecipitation, subcellular fractionation, and confocal microscopy. Cells were submitted to IGF1 stimulation and/or IGF1R pharmacological inhibition (OSI-906). IRS1, β-catenin, and MYC mRNA expression were significantly elevated in ALL patients, compared to normal controls. MYC mRNA expression positively correlated with β-catenin and IRS1. Increased age and MYC expression negatively affected overall survival by univariate analysis. Total and phospho-IGF1R and IRS1, MYC and β-catenin protein expression were higher in ALL cells, compared to normal peripheral blood mononuclear cells (PBMC). IRS1 and β-catenin were found to be colocalized in the nuclei and the cytoplasm of ALL cell lines, whereas both proteins were only slightly detected in the cytoplasm of normal PBMC. In Jurkat cells, a constitutive IRS1 and β-catenin protein interaction were observed; OSI-906 treatment decreased IGF1R tyrosine phosphorylation, IRS1 expression and phosphorylation, nuclear translocation of β-catenin, IRS1 and β-catenin association, and MYC protein expression. In conclusion, the IRS1/β-catenin axis is activated in ALL cells. J. Cell. Biochem. 118: 1774-1781, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)