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INTRODUCTION: Secondary genetic alterations, which contribute to the dysregulation of cell cycle progression and lymphoid specialization, are frequently observed in B-cell precursor acute lymphoblastic leukemia (B-ALL). As IKZF1 and BTG1 deletions are associated with a worse outcome in B-ALL, this study aimed to address whether they synergistically promote glucocorticoid resistance. METHODS: Small interfering RNA was used to downregulate either IKZF1, or BTG1, or both genes in the 207 B-ALL cell line. Cell viability was investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays. The expression levels of IKZF1, BTG1 and glucocorticoid-responsive genes (DUSP1, SGK1, FBXW7 and NR3C1) were evaluated by real time quantitative real time polymerase chain reaction (PCR). RESULTS: Isolated silencing of BTG1, IKZF1, or both genes in combination under dexamethasone treatment increased cell viability by 24%, 40% and 84%, respectively. Although BTG1 silencing did not alter the expression of glucocorticoid-responsive genes, IKZF1 knockdown decreased the transcript levels of DUSP1 (2.6-fold), SGK1 (1.8-fold), FBXW7 (2.2-fold) and NR3C1 (1.7-fold). The expression of glucocorticoid-responsive genes reached even lower levels (reducing 2.4-4 fold) when IKZF1 and BTG1 silencing occurred in combination. CONCLUSIONS: IKZF1 silencing impairs the transcription of glucocorticoid-responsive genes; this effect is enhanced by concomitant loss of BTG1. These results demonstrate the molecular mechanism by which the combination of both genetic deletions might contribute to higher relapse rates in B-ALL.

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Aquatic ecosystems are among the most affected by anthropogenic impacts, and the rapid detection and measurement of these impacts are of great importance for the maintenance of such environments. The order of aquatic insects Odonata has emerged as an important bioindicator of environmental quality due to its sensitivity to environmental changes and its ecophysiological requirements, which make them closely associated with habitat conditions. The aim of this study was to test whether the Zygoptera/Anisoptera ratio can be used as an effective tool to assess anthropogenic changes in Cerrado streams. Our hypothesis is that the proportion of Zygoptera/Anisoptera is an efficient tool for measuring environmental alterations in Cerrado streams, with a positive relationship between habitat integrity and the proportion of Zygoptera and an inverse relationship with the proportion of Anisoptera. Adults were collected in 44 streams of the Cerrado Biome in the eastern Maranhão state. The Habitat Integrity Index (HII) was used to verify the environmental gradient. Our hypothesis was corroborated, with a positive relationship between the richness and abundance of Zygoptera and HII, while an inverse relationship was observed for Anisoptera. According to our results, streams exhibiting a Zygoptera abundance of 68% or higher and richness of 58% or higher can be classified as preserved, while those showing an Anisoptera abundance and richness surpassing 31% and 41%, respectively, may be deemed altered. The patterns detected in the Cerrado were similar to those found in studies of the Amazon Biome and the Atlantic Forest, confirming the effectiveness of this method even for naturally open environments, such as the Cerrado. We conclude, therefore, that this method can be used as a tool to generate rapid results in monitoring studies, with low cost and easy application, enabling the development of mitigation, control, and conservation measures for extremely threatened environments such as those found in the Cerrado Biome.

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Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

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BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

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BACKGROUND: Oncostatin M (OSM) is a pleiotropic cytokine which, after arterial injury, has proven to be to be rapidly expressed. OBJECTIVES: To correlate the serum levels of OSM, soluble OSM receptor (sOSMR), and soluble fraction of glycoprotein 130 (sgp130) in patients with coronary artery disease (CAD) with clinical parameters. METHODS: Levels of sOSMR and sgp130 were evaluated by ELISA and OSM by Western Blot, in patients with CCS (n=100), patients with ACS (n=70), and 64 control volunteers without clinical manifestations of the disease. P-values < 0.05 were considered to be statistically significant. RESULTS: CAD patients exhibited significantly lower levels of sOSMR and sgp130 and higher levels of OSM when compared to the controls (both p < 0.0001). Clinical analysis displayed, lower levels of sOSMR in men ([OR] = 2.05, p = 0.026), youth (OR = 1.68, p = 0.0272), hypertensives (OR = 2.19, p = 0.041), smokers (OR = 2.19, p = 0.017), patients that did not present dyslipidemia (OR = 2.32, p = 0.013), patients with Acute Myocardial Infarction [AMI] (OR = 3.01, p = 0.001) and patients not treated with statin (OR = 1.95, p = 0.031), antiplatelet agent (OR = 2.46, p = 0.005), inhibitors of calcium channels (OR = 3.15, p = 0.028), and antidiabetic drugs (OR = 2.97, p = 0.005). The levels of sOSMR were also correlated with gender, age, hypertension, and use of medications in multivariate analysis. CONCLUSIONS: Our data suggest that the enhanced serum levels of OSM, and decreased levels of sOSMR and sGP130 in patients with cardiac injury may play an important role in the pathophysiological mechanism of the disease. Furthermore, lower levels of sOSMR were associated with gender, age, hypertension, and the use of medications.

FUNDAMENTO: A oncostatina M (OSM) é uma citocina pleiotrópica que, após lesão arterial, demonstra ser expressa rapidamente. OBJETIVOS: Correlacionar os níveis séricos da OSM, do receptor solúvel de oncostatina M (sOSMR) e da fração solúvel de glicoproteína 130 (sgp130) em pacientes com doença arterial coronariana (DAC) a parâmetros clínicos. MÉTODOS: Os níveis de sOSMR e sgp130 foram avaliados por ELISA, enquanto os de OSM foram avaliados por Western Blot, em pacientes com SCC (n=100), pacientes com SCA (n=70) e 64 voluntários do grupo de controle sem manifestações clínicas da doença. Valores de p <0,05 foram considerados estatisticamente significativos. RESULTADOS: Pacientes com DAC exibiram níveis significativamente mais baixos de sOSMR e sgp130 e níveis mais altos de OSM em comparação ao grupo de controle (ambos p <0,0001). A análise clínica mostrou níveis mais baixos de sOSMR em homens ([OR] = 2,05, p = 0,026), jovens (OR = 1,68, p = 0,0272), hipertensos (OR = 2,19, p = 0,041), fumantes (OR = 2,19, p = 0,017), pacientes que não apresentavam dislipidemia (OR = 2,32, p = 0,013), pacientes com infarto agudo do miocárdio [IAM] (OR = 3,01, p = 0,001) e pacientes não tratados com estatina (OR = 1,95, p = 0,031), antiplaquetário (OR = 2,46, p = 0,005), inibidores dos canais de cálcio (OR = 3,15, p = 0,028) e antidiabéticos (OR = 2,97, p = 0,005). Os níveis de sOSMR também foram correlacionados a sexo, idade, hipertensão e uso de medicamentos na análise multivariada. CONCLUSÕES: Nossos dados sugerem que o aumento dos níveis séricos de OSM e a diminuição dos níveis de sOSMR e sGP130 em pacientes com injúria cardíaca podem desempenhar um papel importante no mecanismo fisiopatológico da doença. Além disso, níveis mais baixos de sOSMR foram associados a sexo, idade, hipertensão e uso de medicamentos.

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Neurological symptoms have been often reported in COVID-19 disease. In the present study, we evaluated brain damage associated with the increase of serum levels of neurological biomarkers S100B and neuron-specific enolase (NSE) induced by SARS-CoV-2 infection, in a population from Northeastern Brazil. Thirty-six healthy control (G1) individuals and 141 patients with confirmed COVID-19 were enrolled in this study. Positive-COVID-19 patients were divided into two groups according to the severity of illness by the National Institute of Health (NIH) criteria, 76 patients with mild symptoms for COVID-19 and (G2) and 65 with acute respiratory conditions requiring supplemental oxygenation via intensive care unit (ICU) admission (G3). A follow-up study was conducted with 23 patients from G2 14 (D14) and 21 (D21) days after the onset of symptoms. Serum levels of NSE and S100B were measured using the enzyme-linked immunoassay method (ELISA). Results revealed a significant positive association between G3 patients and S100B serum expression (p = 0.0403). The serum levels of NSE were also significantly enhanced in the G3 group compared to the control (p < 0.0001) and G2 group (p < 0.0001). In addition, clinical features such as symptoms and oxygenation status were not correlated with NSE or S100B serum expression. The follow-up study demonstrated a decrease over time (21 days) in NSE serum expression (p < 0.0001). These results suggest that brain damage is followed by acute virus exposure, with no long-term effects. Future work examining COVID-19 recovery will shed light on chronic neurological damage of SARS-CoV-2 infection.

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Resumo Fundamento A oncostatina M (OSM) é uma citocina pleiotrópica que, após lesão arterial, demonstra ser expressa rapidamente. Objetivos Correlacionar os níveis séricos da OSM, do receptor solúvel de oncostatina M (sOSMR) e da fração solúvel de glicoproteína 130 (sgp130) em pacientes com doença arterial coronariana (DAC) a parâmetros clínicos. Métodos Os níveis de sOSMR e sgp130 foram avaliados por ELISA, enquanto os de OSM foram avaliados por Western Blot, em pacientes com SCC (n=100), pacientes com SCA (n=70) e 64 voluntários do grupo de controle sem manifestações clínicas da doença. Valores de p <0,05 foram considerados estatisticamente significativos. Resultados Pacientes com DAC exibiram níveis significativamente mais baixos de sOSMR e sgp130 e níveis mais altos de OSM em comparação ao grupo de controle (ambos p <0,0001). A análise clínica mostrou níveis mais baixos de sOSMR em homens ([OR] = 2,05, p = 0,026), jovens (OR = 1,68, p = 0,0272), hipertensos (OR = 2,19, p = 0,041), fumantes (OR = 2,19, p = 0,017), pacientes que não apresentavam dislipidemia (OR = 2,32, p = 0,013), pacientes com infarto agudo do miocárdio [IAM] (OR = 3,01, p = 0,001) e pacientes não tratados com estatina (OR = 1,95, p = 0,031), antiplaquetário (OR = 2,46, p = 0,005), inibidores dos canais de cálcio (OR = 3,15, p = 0,028) e antidiabéticos (OR = 2,97, p = 0,005). Os níveis de sOSMR também foram correlacionados a sexo, idade, hipertensão e uso de medicamentos na análise multivariada. Conclusões Nossos dados sugerem que o aumento dos níveis séricos de OSM e a diminuição dos níveis de sOSMR e sGP130 em pacientes com injúria cardíaca podem desempenhar um papel importante no mecanismo fisiopatológico da doença. Além disso, níveis mais baixos de sOSMR foram associados a sexo, idade, hipertensão e uso de medicamentos.

Abstract Background Oncostatin M (OSM) is a pleiotropic cytokine which, after arterial injury, has proven to be to be rapidly expressed. Objectives To correlate the serum levels of OSM, soluble OSM receptor (sOSMR), and soluble fraction of glycoprotein 130 (sgp130) in patients with coronary artery disease (CAD) with clinical parameters. Methods Levels of sOSMR and sgp130 were evaluated by ELISA and OSM by Western Blot, in patients with CCS (n=100), patients with ACS (n=70), and 64 control volunteers without clinical manifestations of the disease. P-values < 0.05 were considered to be statistically significant. Results CAD patients exhibited significantly lower levels of sOSMR and sgp130 and higher levels of OSM when compared to the controls (both p < 0.0001). Clinical analysis displayed, lower levels of sOSMR in men ([OR] = 2.05, p = 0.026), youth (OR = 1.68, p = 0.0272), hypertensives (OR = 2.19, p = 0.041), smokers (OR = 2.19, p = 0.017), patients that did not present dyslipidemia (OR = 2.32, p = 0.013), patients with Acute Myocardial Infarction [AMI] (OR = 3.01, p = 0.001) and patients not treated with statin (OR = 1.95, p = 0.031), antiplatelet agent (OR = 2.46, p = 0.005), inhibitors of calcium channels (OR = 3.15, p = 0.028), and antidiabetic drugs (OR = 2.97, p = 0.005). The levels of sOSMR were also correlated with gender, age, hypertension, and use of medications in multivariate analysis. Conclusions Our data suggest that the enhanced serum levels of OSM, and decreased levels of sOSMR and sGP130 in patients with cardiac injury may play an important role in the pathophysiological mechanism of the disease. Furthermore, lower levels of sOSMR were associated with gender, age, hypertension, and the use of medications.

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INTRODUCTION: Aberrant fucosylation is closely related to malignant transformation, cancer detection, and evaluation of treatment efficacy. The fucosylation process requires GDP-L-fucose, fucosyltransferases, and fucosidases. In gastric cancer (GC), fucosylation alterations were associated with tumor formation, metastasis inhibition, and multi-drug resistance. It is not clear whether tissue-specific transplantation antigen P35B (TSTA3) and alpha-L-fucosidase 2 (FUCA2) have any effect on the development of GC. MATERIALS AND METHODS: We used immunohistochemistry to assess the expression of TSTA3 and FUCA2 in 71 gastric adenocarcinoma samples and their relationship with clinicopathological parameters. RESULTS: TSTA3 expression was associated with lower histological grade I and II (P = 0.0120) and intestinal type Lauren classification (P = 0.0120). TSTA3 immunopositivity could predict Lauren's classification. Analysis of mRNA expression in GC validation cohorts corroborates the significant TSTA3 association with histological grade observed in our study. However, no associations were found between TSTA3 staining and overall survival. FUCA2 expression was markedly increased in GC tissues compared with non-tumoral tissues (P < 0.0001) and was associated with surgical staging III and IV (P = 0.0417) and advanced histological grade tumor states (P = 0.0125). CONCLUSIONS: Alterations of FUCA2 and TSAT3 immunoexpression could lay the basis for future studies using cell glycosylation as a biomarker for the planning of therapeutic strategy in primary gastric cancer.

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Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Despite progress in the last decades, there are still no reliable biomarkers for the diagnosis of and prognosis for GC. Aberrant sialylation is a widespread critical event in the development of GC. Neuraminidases (Neu) and sialyltransferases (STs) regulate the ablation and addition of sialic acid during glycoconjugates biosynthesis, and they are a considerable source of biomarkers in various cancers. This study retrospectively characterized Neu3 and ST3Gal3 expression by immunohistochemistry in 71 paraffin-embedded GC tissue specimens and analyzed the relationship between their expression and the clinicopathological parameters. Neu3 expression was markedly increased in GC tissues compared with non-tumoral tissues (p<0.0001). Intratumoral ST3Gal3 staining was significantly associated with intestinal subtype (p=0.0042) and was negatively associated with angiolymphatic invasion (p=0.0002) and higher histological grade G3 (p=0.0066). Multivariate analysis revealed that ST3Gal3 positivity is able to predict Lauren's classification. No associations were found between Neu3 staining and clinical parameters. The in silico analysis of mRNA expression in GC validation cohorts corroborates the significant ST3Gal3 association with higher histological grade observed in our study. These findings suggest that ST3Gal3 expression may be an indicator for aggressiveness of primary GC.

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Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

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OBJECTIVES: To analyze and compare, in vitro, the microhardness, sorption, solubility, color stability, and cytotoxicity of three types of resin composites: self-adhesive (SARC) (Dyad Flow (DF)/Kerr), bulk-fill (Filtek Bulk Fill Flow (FBF)/3 M ESPE), and conventional (Filtek Z350XT Flow (Z350)/3 M ESPE). MATERIALS AND METHODS: Thirty cylindrical specimens were prepared using a split metal mold (15 mm × 1 mm), divided into 3 groups (n = 10) according to the material used. Vickers hardness (VH) was calculated from three indentations (300gf/15 s) per specimen. The sorption and solubility were measured according to the ISO 4049:2009 specification after storing in distilled water for 7 days. The color of each resin composite was measured using a portable digital spectrophotometer according to the CIELAB system. After a 7-day immersion in coffee, the color variation (∆E) was calculated. Following the ISO 10993:2012, the cytotoxicity in Vero cells was evaluated through the MTT assay. The results were analyzed using the Kruskal-Wallis test to compare the studied groups. The Wilcoxon test was used to compare the assessments in each studied group. For cytotoxicity analysis, the data were compared by the ANOVA test (α = 0.05). RESULTS: DF showed the lowest VH (28.67), highest sorption (0.543 µg/mm3) and solubility (1.700 µg/mm3), and higher ∆E after 7 days of coffee immersion (p = 0.008). The resin composites studied were considered non-cytotoxic. CONCLUSIONS: The SARC presented inferior mechanical and physical-chemical properties than bulk-fill and conventional resin composites, with comparable cytotoxicity against Vero cells. CLINICAL RELEVANCE: The simplification of the clinical protocol of SARC can minimize the number of possible failures during the restorative technique. However, considering their inferior physical and mechanical properties, their coverage with materials of higher mechanical properties and physical-chemical stability should be considered.

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Abstract Osteoarthritis (OA) encompasses degeneration of articular cartilage, subchondral bone erosions and sclerosis. Chondrocyte apoptosis and an oxygen-deprived microenvironment are essential factors in OA pathogenesis. PAR-4 (Prostate apoptosis response-4) is a pro-apoptotic protein implicated in many pathologies as well as in chondrocyte cell death mechanism. Vitamin D supplementation has been identified as a therapeutic tool for a variety of inflammatory pathologies. In the present manuscript, we investigated whether first, PAR-4 expression is influenced by chondrocytes in a model of OA, in vitro, and second, whether vitamin D modulates PAR-4 expression in the same model. To test our hypothesis, we used the primary culture of murine chondrocytes isolated from the femoral and tibial condyles of wistar rats. The expression of the pro-inflammatory effect interleukin IL-1β was evaluated in the presence and absence of vitamin D. Western blot and immunofluorescence analysis confirmed protein expression. In the normoxia condition, the chondrocytes expressed PAR-4 in the cell nucleus, and in the hypoxic condition, PAR-4 was expressed in the cell cytoplasm. We disclosed that the treatment with Vitamin D decreased PAR-4 (p= 0.0137) and caspase-3 (p= 0.0007) expression. Thus, the results suggested that PAR-4 and caspase-3 proteins could be potential targets for OA.However, we believe that research is needed to identify the mechanisms implicated in the regulation of PAR-4 in OA.

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RESUMO O texto aborda as práticas sexuais e a prevenção do HIV nos circuitos de Homens que fazem Sexo com Homens (HSH) da Região Metropolitana do Recife, embasados em inquérito comportamental com 380 HSH de idade de 18 a 51 anos, e entrevistas com 20 dos respondentes. Os dados analisados foram coletados entre janeiro de 2016 e fevereiro de 2017, quando a Profilaxia Pré-Exposição (PrEP) ainda não estava disponível e a Profilaxia Pós-Exposição (PEP) era pouco conhecida (51,8%) e utilizada (1,3%). O Sexo Anal Desprotegido (SAD) (50,6% em parcerias fixas, 30,2% em casuais) ocorria, geralmente, com parceiros presumidamente negativos para HIV. As sorologias eram inferidas pelos vínculos (estranho, conhecido, amigo, namorado). As emoções (medo, tesão, amor, confiança, nojo, carência) eram importantes na configuração do SAD, normalmente articuladas às vinculações. Observaram-se regimes de prazer dissidentes da heteronormatividade: boca-ânus e boca-pênis; sexo a três e em grupo. Considerando a forte presença de SAD e a alta prevalência de HIV em Recife (21,5%), constatou-se a necessidade de ações educativas que apresentem técnicas da prevenção combinada (camisinha, PrEP, PEP, soroescolha, segurança negociada etc.) mediante narrativas que incorporem vínculos, emoções e regimes de prazer dissidentes, para que, ao se aproximarem dos contextos de usos, possibilitem escolhas mais seguras.

ABSTRACT In this text we address sexual practices and HIV prevention in the circuits of men who have sex with men (MSM) in the Metropolitan Region of Recife (RMR), based on a behavioral survey with 380 MSM, aged between 18 and 51 years, and interviews with 20 of the respondents. The analyzed data were collected between January 2016 and February 2017, when Pre-Exposure Prophylaxis (PrEP) was not yet available and Post-Exposure Prophylaxis (PEP) was little known (51%) and used (1.3%). Unprotected Anal Sex (UAS) (50.6% in steady partners, 30.2% in casual partners) generally occurred between partners who were presumed to be HIV-negative. Serologies were inferred by ties (stranger, acquaintance, friend, boyfriend). Emotions (fear, lust, love, trust, disgust, neediness) were important in UAS configuration, almost always linked to attachments. We observed dissident pleasure regimes of heteronormativity: mouth-anus and mouth-penis; threesome and group sex. Considering the strong presence of UAS and the high prevalence of HIV in Recife (21.5%), we found the need for educational actions that introduce combined prevention techniques (condoms, PrEP, PEP, serochoice, negotiated safety etc.) through narratives that incorporate dissident bonds, emotions, and pleasure regimes, so that, when approaching the contexts of use, they enable safer choices.

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Mitochondrial ATP-sensitive potassium channels (mitoKATP) locate in the inner mitochondrial membrane and possess protective cellular properties. mitoKATP opening-induced cardioprotection (using the pharmacological agent diazoxide) is preventable by antagonists, such as glibenclamide. However, the mechanisms of action of these drugs and how mitoKATP respond to them are poorly understood. Here, we show data that reinforce the existence of a mitochondrial sulfonylurea receptor (mitoSUR) as part of the mitoKATP. We also show how diazoxide and glibenclamide compete for the same binding site in mitoSUR. A glibenclamide analog that lacks its cyclohexylurea portion (IMP-A) loses its ability to inhibit diazoxide-induced swelling. These results suggest that the cyclohexylureia portion of glibenclamide is indispensable for mitoKATP inhibition. Moreover, IMP-A did not suppress diazoxide-induced preconditioning (EC50 10.66 µM) in a rat model of a cardiac ischemia/reperfusion. Importantly, glibenclamide inhibited both diazoxide-induced cardioprotection (IC50 86 nM). We suggest that IMP-A must be used with caution since we found this drug possesses significant inhibitory effects on mitochondrial respiration. We characterized the binding of glibenclamide and diazoxide using a molecular simulation (docking) approach. Using the molecular structure of the ATP binding protein ABCB8 (pointed by others as the mitoSUR) we demonstrate that glibenclamide competitively inhibits diazoxide actions. This was reinforced (pharmacologically) in a competitive antagonism test. Taken together, these results bring valuable and novel insights into the pharmacological/biochemical aspects of mitokATP activation and cardioprotection. This study may lead to the discovery of novel therapeutic strategies that may impact ischemia-reperfusion injury.

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Chronic venous ulcers (CVU) of the lower limbs (LL) are common and cause psychological changes and significant social impact, as they make the patient susceptible to pain, absence from work and social bonds. Some materials are suggested as dressings for the treatment of CVU, but they are expensive and are generally not available for use in public health services. To evaluate the efficacy of the treatment for lower limbs (LL) chronic venous ulcer (CVU) using bacterial cellulose (BC), gel and multi-perforated film associated. A randomized controlled clinical-intervention study was performed among participants with LL CVU, divided into two groups: experimental (EG), treated with BC wound dressing and control (CG), treated with a cellulose acetate mesh impregnated with essential fatty acids (Rayon®). The participants were followed for 180 days, evaluated according to the MEASURE methodology. Thirty-nine patients were treated, 20 from the EG and 19 from the CG. In both groups, the wound area decreased significantly (p < 0.001), the healing rate was similar to the CG. The mean number of dressing changes in the SG was 18.33 ± 11.78, while in the CG it was 55.24 ± 25.81, p < 0.001. The healing dressing of bacterial cellulose, gel and associated film, when stimulating the epithelization of the lesions, showed a significant reduction in the initial area, with a percentage of cure similar to the Rayon® coverage. In addition to requiring less direct manipulation of ulcers.

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BACKGROUND: Penile prostheses are the third option in the treatment of erectile dysfunction, however, despite their proven effectiveness, the occurrence of infections, advanced age of patients and comorbidities are the main limiting factors for this treatment modality. In the continuous search for biointegrated, clinically durable and minimally invasive treatment options, a possible model of penile prosthesis was sought through the use of intracavernous bacterial cellulose (BC) gel, in an experimental model of orchiectomized rabbits. METHODS: Thirty adult New Zealand rabbits were equally distributed into three groups: BC; vehicle and control. Each group was then subdivided according to the follow-up time of 3 and 6 months. Bilateral orchiectomy was performed 3 weeks before injection in the BC and vehicle groups. Pachymetry measurements of the penile axis, diameter and length were performed in situ. Histomorphometry analyzes of the corpora cavernosa (CC), thickness of the tunica albuginea, cell density, collagen and elastic fibers post-injection were also performed, in addition to immunohistochemistry for newly formed vessels. RESULTS: The implant of BC increased both the length and thickness of the penis three and six months after the last injection, with a consequent increase in the diameter of the CC. On the other hand, the filling effect was not observed in the control and vehicle groups, confirming the degradation of this tissue after orchiectomy and the effectiveness of BC as a filling agent. Histomorphometry analyzes corroborate the mass effect of BC integrated into the tissue, permeated by predominantly lymphomononuclear inflammatory infiltrate, multinucleated giant foreign body cells, fibroblasts, elastic fibers and newly formed vessels, without degradation or loss of volume, even after six months of implantation. CONCLUSIONS: Biocompatibility and biointegration to the host tissue make BC a prosperous penile filling material, with local application and minimally invasive.

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Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. The flavonoid quercetin is a potent ROS scavenger, with several beneficial effects for the cardiovascular system, including antihypertrophic effects. Oxidative imbalance has been implicated in cardiac hypertrophy and heart failure. In this work, we tested whether quercetin could attenuate cardiac hypertrophy by improving redox balance and mitochondrial homeostasis. To test this hypothesis, we treated a group of mice with isoproterenol (30 mg/kg/day) for 4 or 8 consecutive days. Another group received quercetin (10 mg/kg/day) from day 5th of isoproterenol treatment. We carried out the following assays in cardiac tissue: measurement of cardiac hypertrophy, protein sulfhydryl, catalase, Cu/Zn and Mn-superoxide dismutase (SOD) activity, detection of H2O2, and opening of the mitochondrial permeability transition pore. The animals treated with isoproterenol for the initial 4 days showed increased cardiac weight/tibia length ratio, decreased protein sulfhydryl content, compromised SOD and catalase activity, and high H2O2 levels. Quercetin was able to attenuate cardiac hypertrophy, restore protein sulfhydryl, and antioxidant activity, in addition to efficiently blocking the H2O2. We also observed that isoproterenol decreases mitochondrial SOD activity, while quercetin reverses it. Strikingly, quercetin also protects mitochondria against the opening of mitochondrial permeability transition pore. Taken together, these results suggest that quercetin is capable of reversing established isoproterenol-induced cardiac hypertrophy through the restoration of cellular redox balance and protecting mitochondria.

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RESUMO

Introduction: Surgery is the most effective treatment for breast cancer; however, several factors can impair the immune system during the perioperative period, including the anesthetic technique. Since metastasis is the leading cause of death, one of the treatment pillars is to prevent cancer progression. This systematic review will focus on the prospective clinical evidence available on anesthesia's role in favoring breast cancer recurrence. Methods: The Cochrane Library, Medline, Embase, LILACs, and Web of Science were electronically searched from inception through December 2020 for randomized controlled trials assessing the association of postoperative recurrence and survival with the use of regional anesthesia, opioids, anesthetic adjuncts, and general anesthesia during surgical resection of breast cancer. In total, 711 articles were retrieved. After title and abstract screening and full-text reviews, five randomized controlled trials were selected. Results: Two studies compared inhalation anesthesia with total intravenous anesthesia, while three compared general anesthesia with regional anesthesia and analgesia. There was no significant association between the anesthetic technique and local recurrence, metastasis, or survival. Conclusion: This systematic review did not find an association between the type of anesthesia performed and a higher breast cancer recurrence rate. Up to this time, there is no clinical evidence to support a specific anesthetic technique for malignant breast tumor resection surgeries.

RESUMO

The aim of the study was to describe the level of satisfaction and absenteeism in the work of professionals in the Academia da Cidade Program (ACP). For this, a cross-sectional, descriptive study with a mixed approach was carried out. For data collection, a self-administered questionnaire was used for 104 professionals of the Program in Recife, Pernambuco. For the analysis of the quantitative data, the software SPSS v.10.0 was used, the results were shown in absolute and relative frequencies. Content analysis was carried out for the open questions about job satisfaction. The professionals stated that they were satisfied with the work, both from the point of view of the management of the Program (66.3%), and in a global manner (63.5%). The link with the users, the performance in health promotion and the teamwork were the aspects that most positively influenced job satisfaction and, conversely, the physical and material structure, the municipal macro management and the salary were those that contributed to the dissatisfaction of the professionals. Absenteeism due to sick leave (66.3%) was the main reason for the withdrawal of professionals from work, and the support of the worker's health specialized team from the municipal health department was not perceived. It can be said that the professionals were satisfied with the work in the ACP, but the working conditions, the remuneration and the valorization from the management are aspects that must be improved. It is also necessary to take care of the provider, since absenteeism due to medical causes, withdrew almost half of the professionals in the period studied

O objetivo do estudo foi descrever o nível de satisfação e o absenteísmo no trabalho dos profissionais do Programa Academia da Cidade (PAC). Para isso, foi realizado um estudo transversal, descritivo, de abordagem mista. Para coleta de dados foi utilizado um questionário autoaplicado para 104 profissionais do Programa em Recife, Pernambuco. Para análise dos dados quantitativos foi utilizado o software SPSS v.10.0, sendo os resultados em frequências relativas e absolutas. Para as questões abertas sobre satisfação no trabalho foi realizada análise de conteúdo. Os profissionais afirmaram estarem satisfeitos no trabalho tanto do ponto de vista da gestão do Programa (66,3%), quanto de uma maneira global (63,5%). O vínculo com os usuários, a atuação na promoção da saúde e a equipe de trabalho foram os aspectos que mais influenciaram positivamente a satisfação no trabalho e de forma contrária, a estrutura física e material, a gestão macro municipal e o salário foram os que contribuíram para a insatisfação dos profissionais. O absenteísmo por licença médica (57,7%) foi o motivo principal do afastamento dos profissionais do trabalho e não tiveram o apoio da equipe especializada em saúde do trabalhador da secretaria de saúde municipal. Pode-se afirmar que os profissionais estavam satisfeitos com o trabalho no PAC, porém as condições de trabalho, a remuneração e a valorização da gestão são aspectos que devem ser melhorados. Faz-se necessário também o cuidado ao cuidador, já que o absenteísmo por causas médicas, afastaram quase metade dos profissionais no período estudado

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