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The lack of synthesized information regarding biodiversity is a major problem among researchers, leading to a pervasive cycle where ecologists make field campaigns to collect information that already exists and yet has not been made available for a broader audience. This problem leads to long-lasting effects in public policies such as spending money multiple times to conduct similar studies in the same area. We aim to identify this knowledge gap by synthesizing information available regarding two Brazilian long-term biodiversity programs and the metadata generated by them. Using a unique dataset containing 1904 metadata, we identified patterns of metadata distribution and intensity of research conducted in Brazil, as well as where we should concentrate research efforts in the next decades. We found that the majority of metadata were about vertebrates, followed by plants, invertebrates, and fungi. Caatinga was the biome with least metadata, and that there's still a lack of information regarding all biomes in Brazil, with none of them being sufficiently sampled. We hope that these results will have implications for broader conservation and management guiding, as well as to funding allocation programs., 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 B.V. All rights reserved.)

Conservation of the genetic diversity through skin and cartilage biobanks represents an essential strategy for maintaining biodiversity. Biobanks for the wild species of the order Rodentia have been little studied. Considering that the cryopreservation technique has specific relationships with the tissue and species of interest, we propose investigating different techniques for preserving tissue integrity and cell viability after cartilage and skin culture from Spix's yellow-toothed cavies. Subsequently, two techniques [solid-surface vitrification (SSV) vs. slow freezing (SF)] were used for cartilage and skin cryopreservation. Tissues not subjected to cryopreservation were used as controls. All tissues were evaluated for morphology and proliferation by histological techniques. Moreover, fragments were cultured, and cells were evaluated for viability, proliferation, metabolism, and apoptosis. Regardless of the cryopreservation technique, no differences were observed for the thickness of the epidermis, dermis, skin, spinous and basal layers, fibroblasts, and proliferative activity regarding the number of nucleolar organizer regions (NOR). SSV ensured better maintenance of epidermal cells, normal chondrocytes, filled gaps, collagen fibers, proliferative activity by NOR area/cell, and reduced perinuclear halos and empty gaps compared to SF. SF ensured the conservation of corneum thickness compared to the control. Although both techniques promoted cell recovery after culture, cells from SF resulted in better subconfluence time and day with cell growth around fragments compared to SSV. In conclusion, both cryopreservation techniques resulted in viable cells after culture. However, SSV promoted better maintenance of tissue morphological integrity, and SF ensured the preservation of all cell quality parameters in Spix's yellow-toothed cavies., Competing Interests: Declarations Competing interest The authors declare no Competing interest., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Helicopter pilots may present chronic low back pain due to vibration exposure and asymmetric posture during flight., Objectives: To analyze the effects of a Pilates-based exercise program on low back pain of helicopter pilots of the Brazilian Air Force., Methods: This is a randomized controlled trial with fifteen helicopter pilots of the Brazilian Air Force, who were assessed for pain intensity (Numerical Pain Rating Scale), disability associated with low back pain, and spine muscle endurance in three positions: trunk extension (Ito test) and left and right lateral bridge. Individuals were randomly distributed into the regular exercises group (REG) (n = 7), oriented to maintain their exercise routine, and Pilates group (PG) (n = 8), which performed an exercise program based on Pilates method twice a week for 12 weeks. Reassessments occurred after 6 and 12 weeks. Data were analyzed on SPSS 20.0 software using a significance level of 5%., Results: PG showed a significant reduction in low back pain after 12 weeks of training compared with REG (mean difference of 3.5 points, p < 0.0001). We also observed increased endurance of trunk extensors (p = 0.002) and right (p = 0.001) and left lateral muscles (p = 0.001) in the PG compared with REG. However, the indexes of disability did not change between groups., Conclusion: Pain intensity was significantly reduced while spine muscle endurance increased in PG compared with REG after intervention; thus, Pilates-based exercises should be considered in physical conditioning programs for helicopter pilots., 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 Ltd. All rights reserved.)

Background: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features., Methods: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis., Results: Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6-5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively)., Conclusion: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome., (© 2024. The Author(s).)

The Oxygen Evolution Reaction (OER) is crucial in various processes such as hydrogen production via water splitting. Several electrocatalysts, including metal oxides, have been evaluated to enhance the reaction efficiency. Zeolitic Imidazolate Framework-67 (ZIF-67) has been employed as a precursor to produce Co 3 O 4 , showing high OER activity. Additionally, the formation of composites with carbon-based materials improves the activity of these materials. Thus, this work focuses on synthesizing ZIF-67 and commercial activated carbon (AC) composites, which were used as precursors to obtain Co 3 O 4 /C electrocatalysts by calculating ZIF-67/C X ( X = 10, 30, and 50, the mass percentage of AC). The obtained materials were thoroughly characterized by employing X-ray powder diffraction (XRD), confirming the cobalt oxide structure with a sphere-like morphology as observed in the TEM images. The presence of oxygen vacancies was confirmed by infrared spectroscopy and EPR measurements. The electrocatalytic performance in the OER was investigated by linear sweep voltammetry (LSV), which revealed an overpotential of 325 mV at 10 mA cm -2 and a Tafel slope value of 65.32 mV dec -1 for Co 3 O 4 /C10, superior in activity to several previously reported studies in the literature and electrochemical stability of up to 8 hours. The reduced value of charge transfer resistance, high double-layer capacitance, and the presence of Co 3+ ions justify the superior performance of the Co 3 O 4 /C10 electrocatalyst.

Background: Immune checkpoint inhibitors (ICIs) revolutionized non-small-cell lung cancer (NSCLC) treatment. However, improving patients' selection for this therapy is needed. Gene expression profile (GEP) is a promising biomarker tool. We assessed the predictive value of 48 onco-immune GEPs in an NSCLC real-world scenario., Methods: Retrospective cohort of Brazilian NSCLC patients treated with ICIs in any line. GEP was assessed in FFPE tumor tissue using the nCounter PanCancer IO360 panel, comprising 770 cancer immune genes., Results: The median age of the 135 patients was 61 years old, most male (57.8 %), history of smoking (83.6 %), ECOG-PS 0-1 (88.7 %), clinical stage IV (91.9 %) and adenocarcinoma (65.1 %). First-line ICI in 40 % of cases, alone or in combination with chemotherapy. The median follow-up was 28 months, overall survival after starting immunotherapy (post-immunotherapy survival - PIS) was 17.8 months, and real-world progression-free survival was 5.5 months. The GEP analysis was possible in 66 patients. We found that 14 different GEPs associated with PIS, namely IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM. TIS and IFN-γ were the most significant GEPs associated with favorable outcomes. The median PIS for patients with high TIS expression was 29.2 versus 15.5 months (HR 0.42; 95 %CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-γ., Conclusions: The TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies., 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 © 2023. Published by Elsevier Inc.)

Aim: This work aimed to investigate the antiviral activity of two 1,4-disubstituted-1,2,3-triazole derivatives ( 1 and 2 ) against Chikungunya virus (CHIKV) replication., Materials & Methods: Cytotoxicity was analyzed using colorimetric assays and the antiviral potential was evaluated using plaque assays and computational tools., Results: Compound 2 showed antiviral activity against CHIKV 181-25 in BHK-21 and Vero cells. Also, this compound presented a higher activity against CHIKV BRA/RJ/18 in Vero cells, like compound 1. Compound 2 exhibited virucidal activity and inhibited virus entry while compound 1 inhibited virus release. Molecular docking suggested that these derivatives inhibit nsP1 protein while compound 1 may also target capsid protein., Conclusion: Both compounds exhibit promising antiviral activity against CHIKV by blocking different steps of virus replication., Competing Interests: Competing interests disclosure The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (© 2023 Future Medicine Ltd.)

High-entropy materials have received notable attention concern on account of their unique structure, tunable properties, and unprecedented potential applications in many fields. In this work, for the first time a NiCoMnZnMg-containing high-entropy glycerolate (HE-Gly) particles has been synthesized using a scalable solvothermal method. The HE-Gly particles were used as a precursor in design of porous high-entropy oxide (HEO) microparticles. The morphological and structural characterizations demonstrate that the temperature of the annealing process, and the composition of the metal ions in the HE-Gly precursors play important roles in determining porosity, crystallinity, and phase separation in HEOs. In fact, HE-Gly exhibited a porous structure of spinel HEOs with secreted MgO phase after annealing process at 800 °C, while the annealing process at 400 °C led to a low-crystallinity spinel phase without phase segregation. Overall, this work describes HE-Gly as a new precursor for altering the composition, crystallinity, and porosity of HEOs. This strategy is scalable for potential high mass productions, paving a new path toward industrial application of high-entropy materials., 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 © 2023 Elsevier Inc. All rights reserved.)

Purpose: Breast cancer molecular subtypes show significant differences in different ethnic groups in the United States, but no study has evaluated genetic ancestry in breast cancer in Brazilian women., Methods: Breast cancer patients from distinct parts of Brazil were evaluated. Molecular subtypes were determined by immunohistochemistry. Genetic ancestry was evaluated using a panel of 46 AIMs (ancestry informative markers), which classified genetic ancestry as European, African, Asian, and Amerindian. PCR products were subjected to capillary electrophoresis and analyzed using GeneMapper 4.0 software. Ancestry was evaluated with Structure v.2.3.3 software. Ancestry was tested for correlations with geographic region and molecular subtype. The chi-square test and ANOVA with Bonferroni adjustment were applied., Results: Genetic ancestry and clinical data were evaluated in 1127 patients. Higher rates of self-reported white ethnicity, European ancestry, and HER-2 -  luminal tumors were identified in the South region, which may influence age at diagnosis and result in a higher rate of early tumors. Conversely, higher rates of African ancestry in the North and Northeast regions, self-reported nonwhite ethnicity, HER-2 +  tumors, and triple-negative tumors were noted. Triple-negative and HER-2 +  tumors were associated with higher advanced and metastatic disease rates at diagnosis, with triple-negative tumors being more frequent in young women., Conclusion: Differences in genetic ancestry, self-reported ethnicity, and molecular subtype were found between Brazilian demographic regions. Knowledge of these features may contribute to a better understanding of age at diagnosis and the molecular distribution of breast cancer in Brazil., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study we explored the previously established leishmanicidal activity of a complementary set of 24 imidazolium salts (IS), 1-hexadecylimidazole (C 16 Im) and 1-hexadecylpyridinium chloride (C 16 PyrCl) against Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) infantum chagasi . Promastigotes of L. amazonensis and L. infantum chagasi were incubated with 0.1 to 100 μM of the compounds and eight of them demonstrated leishmanicidal activity after 48 h - C 10 MImMeS (IC 50 L. amazonensis = 11.6), C 16 MImPF 6 (IC 50 L. amazonensis = 6.9), C 16 MImBr (IC 50 L. amazonensis = 6), C 16 M 2 ImCl (IC 50 L. amazonensis = 4.1), C 16 M 4 ImCl (IC 50 L. amazonensis = 1.8), (C 10 ) 2 MImCl (IC 50 L. amazonensis = 1.9), C 16 Im (IC 50 L. amazonensis = 14.6), and C 16 PyrCl (IC 50 L. amazonensis = 4).The effect of IS on reactive oxygen species production, mitochondrial membrane potential, membrane integrity and morphological alterations of promastigotes was determined, as well as on L. amazonensis -infected macrophages. Their cytotoxicity against macrophages and human erythrocytes was also evaluated. The IS C 10 MImMeS, C 16 MImPF 6 , C 16 MImBr, C 16 M 2 ImCl, C 16 M 4 ImCl and (C 10 ) 2 MImCl, and the compounds C 16 Im and C 16 PyrCl killed and inhibited the growth of promastigote forms of L. amazonensis and L. infantum chagasi in a concentration-dependent manner, contributing to a better understanding of the structure-activity relationship of IS against Leishmania . These IS induced ROS production, mitochondrial dysfunction, membrane disruption and morphological alterations in infective forms of L. amazonensis and killed intracellular amastigote forms in very low concentrations (IC 50 amastigotes ≤ 0.3), being potential drug candidates against L. amazonensis ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baldissera, Fazolo, da Silva, de Santana Filho, da Silva, Rivillo Perez, Klitzke, de Oliveira Soares, Rodrigues Júnior, Peres, Dallegrave, Navegantes-Lima, Monteiro, Schrekker and Torres Romão.)

Four imidazolium-based ionic liquids (IL; 1-butyl-3-methylimidazolium chloride, 1-carboxymethyl-3-methylimidazolium chloride, 1,3-dicarboxymethylimidazolium chloride and 1-(2-hydroxyethyl) -3-methylimidazolium chloride) were tested as compatibilizers of microcrystalline cellulose (MCC). Subsequently, ethanolic IL solutions were prepared; MCC was mixed, and the mixtures were left to evaporate the ethanol at ambient conditions. These modified MCC were characterized and applied as reinforcements (5.0 and 10 phr) in an epoxy resin aiming to manufacture biobased composites with enhanced performances. The IL did not significantly modify the morphological and structural characteristics of such reinforcements. Regarding the thermal stability, the slight increase was associated with the MCC-IL affinity. The IL-modified MCC-epoxy composites presented improved mechanical responses, such as flexural strength (≈22.5%) and toughness behavior (≈18.6%), compared with pure epoxy. Such improvement was also obtained for the viscoelastic response, where the storage modulus at the glassy state depended on the MCC amount and IL type. These differences were associated with stronger hydrogen bonding between IL and epoxy hardener or the IL with MCC, causing a "bridging" effect between MCC and epoxy matrix.

The most prevalent cystic fibrosis (CF)-causing mutation - F508del - impairs the folding of CFTR protein, resulting in its defective trafficking and premature degradation. Small molecules termed correctors may rescue F508del-CFTR and therefore constitute promising pharmacotherapies acting on the fundamental cause of the disease. Here, we screened a collection of triazole compounds to identify novel F508del-CFTR correctors. The functional primary screen identified four hit compounds (LSO-18, LSO-24, LSO-28, and LSO-39), which were further validated and demonstrated to rescue F508del-CFTR processing, plasma membrane trafficking, and function. To interrogate their mechanism of action (MoA), we examined their additivity to the clinically approved drugs VX-661 and VX-445, low temperature, and genetic revertants of F508del-CFTR. Rescue of F508del-CFTR processing and function by LSO-18, LSO-24, and LSO-28, but not by LSO-39, was additive to VX-661, whereas LSO-28 and LSO-39, but not LSO-18 nor LSO-24, were additive to VX-445. All compounds under investigation demonstrated additive rescue of F508del-CFTR processing and function to low temperature as well as to rescue by genetic revertants G550E and 4RK. Nevertheless, none of these compounds was able to rescue processing nor function of DD/AA-CFTR, and LSO-39 (similarly to VX-661) exhibited no additivity to genetic revertant R1070W. From these findings, we suggest that LSO-39 (like VX-661) has a putative binding site at the NBD1:ICL4 interface, LSO-18 and LSO-24 seem to share the MoA with VX-445, and LSO-28 appears to act by a different MoA. Altogether, these findings represent an encouraging starting point to further exploit this chemical series for the development of novel CFTR correctors., Competing Interests: Declaration of competing interest M.D.A., C.D.B. and M.L.-P. are inventors on a patent/patent application related to this work deposited at the Portuguese National Institute of Industrial Property (INPI). The other authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: TP53 is the most frequently mutated gene in lung tumors, but its prognostic role in admixed populations, such as Brazilians, remains unclear. In this study, we aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in non-small cell lung cancer (NSCLC) patients in Brazil., Methods: We analyzed 446 NSCLC patients from Barretos Cancer Hospital. TP53 mutational status was evaluated through targeted next-generation sequencing (NGS) and the variants were biologically classified as disruptive/nondisruptive and as truncating/nontruncating. We also assessed genetic ancestry using 46 ancestry-informative markers. Analysis of lung adenocarcinomas from the cBioportal dataset was performed. We further examined associations of TP53 mutations with patients' clinicopathological features., Results: TP53 mutations were detected in 64.3% (n = 287/446) of NSCLC cases, with a prevalence of 60.4% (n = 221/366) in lung adenocarcinomas. TP53 mutations were associated with brain metastasis at diagnosis, tobacco consumption, and higher African ancestry. Disruptive and truncating mutations were associated with a younger age at diagnosis. Additionally, cBioportal dataset revealed that TP53 mutations were associated with younger age and Black skin color. Patients harboring disruptive/truncating TP53 mutations had worse overall survival than nondisruptive/nontruncating and wild-type patients., Conclusion: TP53 mutations are common in Brazilian lung adenocarcinomas, and their biological characterization as disruptive and truncating mutations is associated with African ancestry and shorter overall survival., (© 2023 S. Karger AG, Basel.)

Background: The purpose of this study was to evaluate the status of Epstein-Barr virus (EBV) infection and the expression of programmed cell death ligand-1 (PD-L1) in tumor samples from patients with nasopharyngeal carcinoma (NPC)., Methods: Evaluation of EBV infection was performed through the detection of EBV-encoded small ribonucleic acids (EBER) by in situ hybridization, and PD-L1 expression was performed through immunohistochemistry., Results: In total, 124 samples were evaluated for EBER and 120 for PD-L1 expression. A total of 86.3% of cases were positive for EBER and 55.8% were positive for PD-L1. There was a correlation between EBER positivity and the presence of undifferentiated carcinoma histology ( p = 0.007) as well as the absence of tobacco history ( p = 0.019). There was a correlation between PD-L1 expression and EBER positivity ( p = 0.004). There was no statistically significant difference between overall survival (OS) and EBER ( p = 0.290) or PD-L1 ( p = 0.801) expression., Conclusions: This study corresponds to one of the largest cohorts of NPC in a non-endemic region. Phase III studies with checkpoint inhibitors are ongoing and may provide more data about the role of PD-L1 expression in this disease.

The development of efficient electrocatalysts for the oxygen evolution reaction (OER) is of paramount importance in sustainable water-splitting technology for hydrogen production. In this context, this work reports mixed-valence oxide samples of the Mn X Co 3-X O 4 type (0 ≤ X ≤ 1) synthesized for the first time by the proteic sol-gel method using Agar-Agar as a polymerizing agent. The powders were calcined at 1173 K, characterized by FESEM, XRD, RAMAN, UV-Vis, FT-IR, VSM, and XPS analyses, and were investigated as electrocatalysts for the oxygen evolution reaction (OER). Through XRD analysis, it was observed that the pure cubic phase was obtained for all samples. The presence of Co 3+ , Co 2+ , Mn 2+ , Mn 3+ , and Mn 4+ was confirmed by X-ray spectroscopy (XPS). Regarding the magnetic measurements, a paramagnetic behavior at 300 K was observed for all samples. As far as OER is concerned, it was investigated in an alkaline medium, where the best overpotential of 299 mV vs. RHE was observed for the sample (MnCo 2 O 4 ), which is a lower value than those of noble metal electrocatalysts in the literature, together with a Tafel slope of 52 mV dec -1 , and excellent electrochemical stability for 15 h. Therefore, the green synthesis method presented in this work showed great potential for obtaining electrocatalysts used in the oxygen evolution reaction for water splitting.

Trace and potentially toxic elements represent one class of food contaminants that has stimulated research. In markets, two main methods of growing vegetables are generally available: conventional and organic. Conventional farming has been the target of some concerns about the use of agrochemicals, especially the excessive use of pesticides, whereas organic agriculture minimizes the use of agrochemicals. As the main route for potentially toxic elements' absorption by humans is by food intake, it is important to evaluate if the method of cultivation influences their concentrations. This study evaluated the levels of potentially toxic elements and nutrients on four leafy vegetables: curly lettuce, collard greens, escarole, and rocket, cultivated by conventional and organic farming. We found that Al, Ba, Fe, and Sr levels were higher in conventional samples, whereas K, Pb, and Zn were higher in organic. Amongst the elements analysed, values of Fe, Al, and K were around 0.2, 0.3, and 70 g kg -1 , respectively, except in collard greens, in which the values were lower. On the other hand, Ba, Sr, and Mn presented higher concentration in collard greens compared to the other vegetables in conventional cultivation (~ 35, 80, and 120 mg kg -1 , respectively). The principal component analysis result shows that the samples were grouped according to the type of vegetable, regardless of the type of cultivation. Despite this, the evaluation of the cultivation by different types of farming is important in order to choose the healthiest option., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Despite the developments in cancer research over years, cancer is still one of the leading causes of death worldwide. In Brazil, the number of cancer cases for the several next years (2020-2022) is expected to increase up to 625,000. Thus, translational research has been vital to determine the potential risk, prognostic, and predictive biomarkers in cancer. Therefore, Barretos Cancer Hospital implemented a biobank (BB-BCH) in 2006, which is responsible for processing, storage, and provision of biological materials from cancer and non-cancer participants. Hence, this article aimed to describe BB-BCH's history, experiences, and outcomes and explore its impact on Brazilian translational oncology research scenario. BB-BCH has a multidisciplinary team who are responsible for guaranteeing the quality of all processes as recommended by international guidelines for biobanks. Furthermore, BB-BCH has ample equipment to ensure the quality of all material requested by researchers as genetic material (DNA and RNA) and/or entire biospecimens. From 2006 to 2019, BB-BCH contained 252,069 samples from 44,933 participants, the whole collection is represented by 15 different types of biospecimens collected from them. According to our data, the most collected and stored topography in men is head and neck (29%); in women is breast (28%); and in children is torso and limb (27%) samples. Finally, we supported national and international consortia and projects such as The Cancer Genome Atlas. BB-BCH is a vital knowledge source for scientific community, enabling the development of high-quality studies, with a wide variety of tumor categories and high national representativeness of Brazilian population., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Oral cytopathology is able to detect incipient cellular alterations, but it is not routinely applied to this purpose. We aimed to establish a model to screen individuals with no oral lesion exposed to smoking/alcohol, by means of the nuclear area, cell proliferation rate, and analysis of genetic damage., Methods: In this cross-sectional pilot study, 90 patients were allocated into 3 groups: oral cancer group (patients with oral squamous cell carcinoma), tobacco/alcohol group (patients without oral lesions and exposed to these risk factors), and control group (individuals with no lesion and not exposed to tobacco and alcohol). The cytological smears performed in these individuals were stained with Papanicolaou, a silver-staining and a Feulgen reaction. The nuclei of cells were measured, and AgNORs/nucleus and micronuclei (MN) were quantified. The cutoff values were stipulated evaluating the healthy mucosa (control group) and the cancerization field mucosa (oral cancer group)., Results: Cutoff values for the screening of individuals exposed to carcinogens were ≥8% of nuclei larger than 100 μm2, ≥3.38 AgNOR/nucleus, and ≥3 MN per 1,000 cells., Conclusions: Nuclear area measurement and AgNORs/nucleus and MN quantification identified the incipient phase of oral carcinogenesis. A screening model for individuals without oral lesion exposed to smoking/alcohol was proposed., (© 2021 S. Karger AG, Basel.)

1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against Leishmania amazonensis in vitro infection. After the screening of eleven compounds, compound 4 exhibited better results against L. amazonensis promastigotes (IC 50 = 15.52 ± 3.782 μM) and intracellular amastigotes (IC 50 = 4.10 ± 1.136 μM), 50% cytotoxicity concentration at 84.01 ± 3.064 μM against BALB/c peritoneal macrophages, and 20.49-fold selectivity for the parasite over the cells. Compound 4 induced ultrastructural mitochondrial alterations and lipid inclusions in L. amazonensis promastigotes, upregulated tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-12, and IL-10 messenger RNA expressions, and enhanced the NO production, verified by nitrite ( p = 0.0095) and inducible nitric oxide synthase expression ( p = 0.0049) quantification, which played an important role in its activity against intramacrophagic L. amazonensis . In silico prediction in association with antileishmanial activity results showed compound 4 as a hit compound with promising potential for further studies of new leishmaniasis treatment options.

Background: The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer., Methods: A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter ® PanCancer Pathways Panel , which contains 770 genes., Results: The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9 . The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%., Conclusion: We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Andrade, da Silva, Laus, de Lima, Berardinelli, da Silva, Matsushita, Bonatelli, da Silva, Evangelista, Carvalho, Reis and dos Reis.)

Glioblastoma is the most lethal tumor of the central nervous system, presenting a very poor prognostic, with a survival around 16 months. The interaction of mesenchymal stem cells and tumor cells has been studied, showing a bias in their role favoring or going against aggressiveness. Natural products such as flavonoids have showed their anticancer properties and the synergic potential with the activation of microenvironment cells to inhibit tumor progression. Agathisflavone is a flavonoid studied in neurodegenerative diseases and cancer. The present study investigated the effect of flavonoid in the viability of heterogeneous glioblastoma (GBM) cells considering a coculture or conditioned medium of mesenchymal stem cells (MSCs) effect, as well as the dose-dependent effect of this flavonoid in tumor migration and differentiation via STAT3. Agathisflavone (3-10 μM) induced dose-dependent toxicity to GL-15 and U373 human GBM cells, since 24 h after treatments. It was not toxic to human MSC but modified the pattern of interaction with GBM cells. Agathisflavone also inhibited migration and increased differentiation of human GBM cells, associated with the reduction on the expression of STAT3. These results demonstrate that the flavonoid agathisflavone had a direct anti-glioma effect. However, could be observed its effect in MSCs response that may have an impact in controlling GBM growth and aggressiveness, an important factor to consider for new therapies., (© 2020 Wiley Periodicals LLC.)

Competing Interests: Josiane M. DiasSpeakers' Bureau: AstraZenecaResearch Funding: BMS Brazil, Merck, Ipsen, Novartis, Roche, Janssen, MSD Pedro De MarchiHonoraria: SanofiConsulting or Advisory Role: Merck Sharp & Dohme, AstraZeneca, Bristol- Myers Squibb, Roche, BayerSpeakers' Bureau: Merck Sharp & Dohme, Bristol Myers Squibb, Roche, AstraZeneca, Novartis, Merck, Boehringer IngelheimResearch Funding: AstraZeneca, Amgen, Merck Sharp & Dohme, RocheTravel, Accommodations, Expenses: Merck Sharp & Dohme, AstraZeneca, Roche, Bristol Myers Squibb Leticia F. LealResearch Funding: AstraZeneca do Brasil Rui M. ReisResearch Funding: MSD OncologyNo other potential conflicts of interest were reported.

Background: Stroke is the principal cause of disability around the world and the ensuing functional dependence (FD) can be correlated with different factors., Objective: To determine how demographic factors and clinical characteristics after stroke distinguish patients who achieve functional independence from those who do not., Design and Setting: Observational study at specialized neurovascular clinic in Alagoas, Brazil., Methods: FD was classified according to the modified Rankin scale (mRs): 0 to 2 points were classified as independent (FD-), and 3 to 5 points were classified as dependent (FD+). Logistic regression analysis included age, sedentary lifestyle, the Center for Epidemiological Studies - Depression Scale (CES-D) and the National Institutes of Health Stroke Scale (NIHSS). The Mann-Whitney test and χ2 test were used to compare groups., Results: We included 190 stroke patients with a mean age of 60.02 ± 14.22 years. We found that 34.8% of the patients were classified as FD+. Lower NIHSS and CES-D scores were more associated with achieving functional independence. Most of the patients had access to physical therapy, and the mean duration of rehabilitation therapy was 65.2 minutes per week. Females had higher prevalence of depressive symptoms (P = 0.005) and rehabilitation time was shorter for hemorrhagic stroke (P = 0.02)., Conclusion: We found a FD rate four times greater than in another Brazilian study. Lower stroke severity and fewer depressive symptoms were associated with achieving functional independence. Less than half of the patients were referred to a rehabilitation service at hospital discharge and few had access to multidisciplinary treatment.

Cobalt-based oxides are among the most promising electrocatalysts for oxygen evolution reactions (OER). In this context, this work reports the synthesis of manganese-doped cobaltites using the Zeolitic-Imidazolate Frameworks 67 (ZIF-67) as template. The incorporation of manganese ions into ZIF-67 structure was evaluated in ethanol and methanol, in order to obtain the best synthetic route. Non-doped (ZIF-67C) and Mn-doped cobaltites (Mn/ZIF-67C(E) and Mn/ZIF-67C(M)) were obtained after thermal treatment at 350 °C. Structural and morphological properties were investigated and presence of Mn 3+ and Mn 4+ was confirmed by X-ray photoelectron spectroscopy (XPS) data and magnetization curves. The electrocatalytic activity in OER was investigated in alkaline medium for manganese cobaltites, and compared to the ZIF-67C. Overpotentials to generate a current of 10 mA cm -2 were 338 mV and 356 mV for Mn/ZIF-67C(E) and Mn/ZIF-67C(M), respectively. These results are superior to those found for similar materials in the literature. The material obtained in methanol (Mn/ZIF-67C(M)) presents lower overpotential, however, shows superior electrocatalytic performance for current density above 100 mA cm -2 , therefore being an efficient electrode for commercial electrolysers., 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 © 2020 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Jatropha curcas L. (Euphorbiaceae), a medicinal plant known in Brazil as "Pinhão Manso", is highly adaptable, being cultivated in different tropical and subtropical regions of the world. Antimicrobial, antioxidant and antiinflammatory activities have been attributed to different parts of the plant. In the central nervous sytem (CNS), neuroinflammation is mediated by glial cells, mainly by astrocytes and microglia, a process that plays an important role in neurodegenerative diseases and other CNS disorders. In this study, we investigated the anti-inflammatory activity of the methanolic extract obtained from the leaves of J. curcas L. (MEJc) in primary cultures of glial cells submited to inflammatory stimulus., Materials and Methods: Primary cultures of glial cells obtained from the cerebral cortex of neonate Wistar rats were treated with MEJc (0.1-50,000 μg mL -1 ) and its fractions (F n Jc) (0.1 μg mL -1 ) with or without lipopolysaccharide of Escherichia coli (LPS) (1 μg mL -1 ). Cell viability was determined with MTT test. Modifications in glial cell morphology were investigated by means of phase contrast microscopy and May-Grünwald staining. The reactivity of astrocytes and microglia were investigated with immunocytochemistry for GFAP, Iba1 and transcription factor NF-kB, as well as with Greiss reaction to determine the nitric oxide (NO) production., Results: MEJc at 0.1-1000 μg mL -1 was non-toxic to glial cells and the DE 50 was 10.794 μg mL -1 . The treatment with LPS induced the activation of astrocytes and microglia marked by morphological modifications and changes in the expression of GFAP and Iba1, as well as the increase in NF-kB expression and NO production. Treatment with MEJc inhibited the morphological modifications, changes in GFAP and Iba1 expression, and the increase in NF-kB and NO production induced by LPS., Conclusion: This study demonstrates that the MEJc and its fractions modulate inflammatory response of astrocytes and microglia to LPS and may be considered as a potential therapeutic strategy for neuroinflammation-related diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Oral lesions has been reported in coronavirus disease 2019 (COVID-19). However, there are gaps about the occurrence. The aim of this study was to describe the clinical characteristics of oral lesions in patients with COVID-19., Methods: A systematic review was conducted in four electronic databases (PubMed, Lilacs, Cochrane and Google Scholar) with the search terms: "coronavírus", "COVID-19", "SARS-CoV-2", "novel coronavírus", "2019nCoV", "oral manifestation", "mucosal lesions", "oral lesions", "mucosa viral lesions" and "oral conditions". Articles were limited to those published between january and july 2020, and in English., Results: Initially, 182 articles were found, after reading the titles and abstracts a total of 24 records were included for full-text reading. Finally, 22 articles were included for data extraction and assessement. We identified and subsequently discussed clinical characteristics and differential diagnosis., Conclusions: The etiology of many oral mucosal lesions is intimately related to infectious, immunological, and psychosocial factors. Therefore, amid the SARS-CoV-2 pandemic in which many doubts about the disease still remain, caution is needed when evaluating patients and establishing correlations with other diseases that could be associated.

This work reports the effects of microstructural changes due to the secondary phases, in particular sigma ( σ ), on the mechanical properties and electrochemical behavior of thermally aged duplex stainless steel (DSS). Structural, morphological, mechanical, and electrochemical characterizations were performed. Sigma phase content increased with increasing aging treatment time. It had a net-like shape, as observed by electron backscatter diffractometry (EBSD). Its presence directly damaged mechanical properties. The corrosion assessment included electrochemical impedance spectroscopy (EIS) in 1 M NaCl solution at temperatures of 25, 40, and 65 °C. EIS results demonstrate that an increase in the σ phase content decreased the corrosion resistance (21.1-0.8, 3.5-0.3, and 3.1-0.2 kΩ cm 2 at 25, 40, and 60 °C, respectively).

Epidermal growth factor (EGF) and its receptor (EGFR) play a paramount role in lung carcinogenesis. The polymorphism in the EGF promoter region EGF+61A>G (rs4444903) has been associated with cancer susceptibility, but its role in lung cancer patients treated with tyrosine kinase inhibitors (TKIs) remains unknown. Here, we aimed to evaluate the predictive and prognostic role of EGF+61A>G SNP in lung cancer from Brazilian EGFR-mutated TKI-treated patients. Herein, patients carrying EGFR-sensitizing mutations submitted to TKI treatment (gefitinib/erlotinib) were analyzed (n = 111) for EGF+61A>G genotype by TaqMan genotyping assay. TKI treatment was classified as partial response (PR), stable disease (SD), and disease progression (DP), according to RECIST1.1. Association analysis was assessed by chi-square and Fisher's test (univariate) and multinomial model (multivariate) and survival analysis by Kaplan-Meier method and log-rank test. The EGF+61A>G genotype frequencies observed were: AA = 31.5% (n = 35), AG = 49.6% (n = 55) and GG = 18.9% (n = 21). The allelic frequencies were 56.3% for A, and 43.7% for G and the population was in Hardy-Weinberg equilibrium (P = 0.94). EGF+61A>G codominant model (AA vs. AG vs. GG) was associated with a response to TKIs (P = 0.046), as well as a recessive model (AA vs. AG + GG; P = 0.023). The multinomial regression showed an association between the codominant model (AG) and recessive model (AG + GG) with SD compared with DP (P = 0.01;OR = 0.08; 95% CI = 0.01-0.60 and P = 0.02;OR = 0.12; 95% CI = 0.20-0.72, respectively). No association between genotypes and progression-free or overall survival was observed. In conclusion, the EGF+61 polymorphism (AG and AG + GG) was independently associated with stable disease in lung cancer patients although it was not associated with the overall response rate to first-generation TKIs or patient outcome., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: Although doxorubicin is widely used to treat cancer, severe side effects limit its clinical use. Combination of standard chemotherapy with natural products can increase the efficacy and attenuate the side effects of current therapies. Here we studied the anticancer effects of a combined regimen comprising doxorubicin and [10]-gingerol against triple-negative breast cancer, which does not respond to hormonal or targeted therapies., Methods: Cytotoxicity was evaluated by MTT assay, cell cycle progression and apoptosis were analyzed by flow cytometry and signaling pathways were analyzed by Western blotting in human and murine triple negative breast cancer cell systems. The anticancer/antimetastatic and toxic effects of the combined regimen was evaluated using syngeneic and xenograft orthotopic models., Results: The combination of doxorubicin and [10]-gingerol significantly increased the number of apoptotic cells, compared to each compound alone. In 4T1Br4 cells, the combined regimen was the only condition able to increase the levels of active caspase 3 and γH2AX and to decrease the level of Cdk-6 cyclin. In vivo, doxorubicin (3 mg/Kg, D3) and [10]-gingerol (10 mg/Kg, G10) resulted in a significant reduction in the volume of primary tumors and a decrease in the number of circulating tumor cells (CTCs). Interestingly, only the combined regimen led to decreased tumor burdens to distant organs (i.e., metastasis) and reduced chemotherapy-induced weight loss and hepatotoxicity in tumor-bearing animals. Likewise, in a xenograft model, only the combined regimen was effective in significantly reducing the primary tumor volume and the prevalence of CTCs., Conclusions: Our data indicate that [10]-gingerol has potential to be used as a neoadjuvant or in combined therapy with doxorubicin, to improve its anticancer activity.

Coronavirus disease 2019 (COVID-19) is a multisystemic condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with manifestations ranging from mild upper respiratory symptoms to cytokine storm causing acute respiratory distress syndrome. Pancreatic exocrine tissue and endocrine islets both express angiotensin-converting enzyme 2 (ACE2), the proven receptor for SARS-CoV-2 cell internalization. An increase in pancreatic enzymes has been increasingly recognized in patients with COVID-19, but little is known about the real prevalence of acute pancreatitis in this population. We report a case of acute acalculous pancreatitis in a COVID-19 patient., Learning Points: Acute pancreatitis may be a manifestation of SARS-CoV-2 infection.Future studies must address the real impact of pancreatic involvement in COVID-19 patients., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Background: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis. Aberrant miRNA expression has been frequently reported in sporadic breast cancers, but few studies have focused on profiling hereditary breast cancers. In this study, we aimed to identify specific miRNA signatures in hereditary breast tumors and to compare with sporadic breast cancer and normal breast tissues., Methods: Global miRNA expression profiling using NanoString technology was performed on 43 hereditary breast tumors (15 BRCA1, 14 BRCA2, and 14 BRCAX), 23 sporadic breast tumors and 8 normal breast tissues. These normal breast tissues derived from BRCA1- and BRCA2- mutation carriers (n = 5) and non-mutation carriers (n = 3). Subsequently, we performed receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performance of differentially expressed miRNAs. Putative target genes of each miRNAs considered as potential biomarkers were identified using miRDIP platform and used for pathway enrichment analysis., Results: miRNA expression analyses identified several profiles that were specific to hereditary breast cancers. A total of 25 miRNAs were found to be differentially expressed (fold change: > 2.0 and p < 0.05) and considered as potential biomarkers (area under the curve > 0.75) in hereditary breast tumors compared to normal breast tissues, with an expressive upregulation among BRCAX cases. Furthermore, bioinformatic analysis revealed that these miRNAs shared target genes involved in ErbB, FoxO, and PI3K-Akt signaling pathways., Conclusions: Our results showed that miRNA expression profiling can differentiate hereditary from sporadic breast tumors and normal breast tissues. These miRNAs were remarkably deregulated in BRCAX hereditary breast cancers. Therefore, miRNA signatures can be used as potential novel diagnostic biomarkers for the prediction of BRCA1/2- germline mutations and may be useful for future clinical management.

Autophagy is a cell-survival pathway with dual role in tumorigenesis, promoting either tumor survival or tumor death. WNK2 gene, a member of the WNK (with no lysine (K)) subfamily, acts as a tumor suppressor gene in gliomas, regulating cell migration and invasion; however, its role in autophagy process is poorly explored. The WNK2 -methylated human glioblastoma cell line A172 WT (wild type) was compared to transfected clones A172 EV (empty vector), and A172 WNK2 (WNK2 overexpression) for the evaluation of autophagy using an inhibitor (bafilomycin A1-baf A1) and an inducer (everolimus) of autophagic flux. Western blot and immunofluorescence approaches were used to monitor autophagic markers, LC3A/B and SQSTM1/p62. A172 WNK2 cells presented a significant decrease in LC3B and p62 protein levels, and in LC3A/B ratio when compared with control cells, after treatment with baf A1 + everolimus, suggesting that WNK2 overexpression inhibits the autophagic flux in gliomas. The mTOR pathway was also evaluated under the same conditions, and the observed results suggest that the inhibition of autophagy mediated by WNK2 occurs through a mTOR-independent pathway. In conclusion, the evaluation of the autophagic process demonstrated that WNK2 inhibits the autophagic flux in glioblastoma cell line.

Background: Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1 alerts for the urgency in developing new antivirals with other therapeutic targets. Thus, this study evaluated a series of 1,4-disubstituted-1,2,3-triazole derivatives against HSV-1 acute infection and provided deeper insights into the possible mechanisms of action., Methods: Human fibroblast cells (HFL-1) were infected with HSV-1 17syn+ and treated with the triazole compounds at 50 μM for 24 h. The 50% effective drug concentration (EC 50 ) was determined for the active compounds. Their cytotoxicity was also evaluated in HFL-1 with the 50% cytotoxic concentration (CC 50 ) determined using CellTiter-Glo ® solution. The most promising compounds were evaluated by virucidal activity and influence on virus egress, DNA replication and transcription, and effect on an acyclovir-resistant HSV-1 strain., Results: Compounds 3 ((E)-4-methyl-N'-(2-(4-(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylenebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde) were the most promising, with an EC 50 of 16 and 21 μM and CC 50 of 285 and 2,593 μM, respectively. Compound 3 was able to inhibit acyclovir-resistant strain replication and to interfere with virus egress. Both compounds did not affect viral DNA replication, but inhibited significantly the expression of ICP0, ICP4 and gC. Compound 4 also affected the transcription of UL30 and ICP34.5., Conclusions: Our findings demonstrated that these compounds are promising antiviral candidates with different mechanisms of action from acyclovir and further studies are merited.

Objectives: In this study hybrid nanofibers embedded with niobium pentoxide (Nb 2 O 5 ) were synthesized, incorporated in self-adhesive resin cement, and their influence on physical-properties was evaluated., Methods: Poly(D,L-lactide), PDLLA cotton-wool-like nanofibers with and without silica-based sol-gel precursors were formulated and spun into submicron fibers via solution blow spinning, a rapid fiber forming technology. The morphology, chemical composition and thermal properties of the spun fibers were characterized by field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC), respectively. Produced fibers were combined with a self-adhesive resin cement (RelyX U200, 3M ESPE) in four formulations: (1) U200 resin cement (control); (2) U200+1wt.% PDLLA fibers; (3) U200+1wt.% Nb 2 O 5 -filled PDLLA composite fibers and (4) U200+1wt.% Nb 2 O 5 /SiO 2 -filled PDLLA inorganic-organic hybrid fibers. Physical properties were assessed in flexure by 3-point bending (n=10), Knoop microhardness (n=5) and degree of conversion (n=3). Data were analyzed with One-way ANOVA and Tukey's HSD (α=5%)., Results: Composite fibers formed of PDLLA-Nb 2 O 5 exhibited an average diameter of ∼250nm, and hybrid PDLLA+Nb 2 O 5 /SiO 2 fibers were slightly larger, ∼300nm in diameter. There were significant differences among formulations for hardness and flexural strength (p<0.05). Degree of conversion of resin cement was not affected for all groups, except for Group 4 (p<0.05)., Significance: Hybrid reinforcement nanofibers are promising as fillers for dental materials. The self-adhesive resin cement with PDLLA+Nb 2 O 5 and PDLLA+Nb 2 O 5 /SiO 2 presented superior mechanical performance than the control group., (Copyright © 2019 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Background: Endometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer., Methods: A case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging., Results: Twenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031)., Conclusion: Our data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence., Competing Interests: The authors have declared that no competing interests exist.

Alterations in nuclear size and shape are commonly observed in cancers, and its objective evaluation may provide valuable clinical information about the outcome of the disease. Here, we applied the nuclear morphometric analysis in tissues in hematoxylin and eosin-digitized slides of nevi and melanoma, to objectively contribute to the prognostic evaluation of these tumors. To this, we analyzed the nuclear morphometry of 34 melanomas classified according to the TNM stage. Eight cases of melanocytic nevi were used as non-neoplastic tissues to set the non-neoplastic parameters of nuclear morphology. Our samples were set as G1 (control, nevi), G2 (T1T2N0M0), G3 (T3T4N0M0), G4 (T1T2N1M1), and G5 (T3T4N1M1). Image-Pro Plus 6.0 software was used to acquire measurements related to nuclear size (variable: Area) and shape (variables: Aspect, AreaBox, Roundness, and RadiusRatio, which were used to generate the Nuclear Irregularity Index). From these primary variables, a set of secondary variables were generated. All the seven primary and secondary variables related to the nuclear area were different among groups (Pillai's trace P<0.001), whereas Nuclear Irregularity Index, which is the variable related to nuclear shape, did not differ among groups. The secondary variable 'Average Area of Large Nuclei' was able to differ all pairwise comparisons, including thin nonmetastatic from thin metastatic tumors. In conclusion, the objective quantification of nuclear area in hematoxylin and eosin slides may provide objective information about the risk stratification of these tumors and has the potential to be used as an additional method in clinical decision making.

Background: Renal fibrosis is the result of the interaction of cellular and molecular pathways, which is induced by sustained glomerular injury and involves the podocytes and multiple profibrotic factors. In this study, we investigated the correlation of the mRNA expression of podocyte proteins and profibrotic factors with renal fibrosis measured in renal biopsies of patients with primary and secondary glomerulopathies., Methods: Eighty-four adult patients with primary or secondary glomerular diseases and 12 controls were included. Demographic and clinical data were collected. Seventy-two percent of the renal biopsies were done less than one year from clinical disease manifestation. The quantification of the podocyte-associated mRNAs of alpha-actinin-4, podocin, and podocalyxin, as well as of the profibrotic factors TGF-β1, CTGF, and VEGF-A were quantified by real-time polymerase chain reaction. The percent positive area of renal fibrosis was measured by immunohistochemistry staining, using anti-CTGF and anti-HHF35 antibodies and unpolarized Sirius Red. Correlations between the expression of tissue mRNAs and the positive area of fibrosis for the measured markers were made by Spearman's rank correlation coefficient., Results: In relation to control biopsies, podocyte-specific proteins were downregulated in podocytopathies, in proliferative nephritis, in diabetic kidney disease (DRD), and in IgA nephropathy (IgAN). Messenger RNA of TGF-β1, CTGF, and VEGF-A was upregulated in patients with podocytopathies and in DRD but not in proliferative nephritis and IgAN. Tissue mRNA expression of TGF-β1, CTGF, and VEGF-A were strongly correlated with renal fibrosis, as measured by HHF35; however, the correlation, albeit significant, was moderate for Sirius Red and weak for CTGF. The percent positive area of renal fibrosis measured by Sirius Red was similar between podocytopathies and DRD and significantly higher in podocytopathies compared to IgAN or proliferative nephritis., Conclusions: In patients with glomerular diseases, the mRNA of TGF-β1, CTGF, and VEGF-A correlated positively with the extent of renal fibrosis, and the positive area of fibrosis was larger in the podocytopathies and in DRD as measured by Sirius Red. The pathways connecting podocyte damage and activation of profibrotic factors to kidney tissue fibrosis need to be better investigated., Competing Interests: The authors have declared that no competing interests exist.

Background: The combined association of physical activity and sedentary behavior with adverse health factors is not yet clear in the literature. A combined analysis of physical activity level and sedentary behavior may provide evidence of the interrelation between these behavioral variables and the frailty syndrome. Thus, the aim of this study was to examine the relationship between physical activity level, sedentary behavior and frailty in older adults., Methods: In this study, we evaluated 457 older adults (age range = 60 to 96 years old) from the Longitudinal Study of the Elderly Health of Alcobaça, Bahia. The frailty condition was defined by the presence of three or more of the following criteria: unintentional weight loss, slow walking speed measured over a 4.57 m test, a reduction of manual grip strength and exhaustion. Based upon these criteria, participants were classified as non-frail or frail. Physical activity level and time spent in sedentary behavior were assessed with the International Questionnaire of Physical Activity. Descriptive statistics were used to characterize the sample. To examine the combined association of physical activity and sedentary behavior with frailty, chi-square and Poisson regression tests were used. Statistical significance was defined as p ≤ 0.05., Results: The prevalence of frailty was 8.8% (n = 40), with higher prevalence observed with increasing age. Low physical activity level combined with excessive time spent in sedentary behavior (physical activity level < 150 min/wk. and sedentary behavior ≥540 min/day) was associated with frailty, resulting in a prevalence ratio of 2.83 (95% CI, 1.23 to 6.52)., Conclusion: Frailty is more prevalent among older adults who exhibit insufficient levels of physical activity combined with a great amount of time spent in sedentary behavior, even when adjusted for sociodemographic factors.

Purpose: To estimate the effect size of a serious game for cardiopulmonary resuscitation (CPR) training in comparison with a video-based on-line course in terms of learning outcomes among medical students before simulation-based CPR using a manikin., Methods: Participants were 45 first-year medical students randomly assigned to CPR self-training using either a video-based Apple Keynote presentation (n = 22) or a serious game developed in a 3D learning environment (n = 23) for up to 20 min. Each participant was evaluated on a written, multiple-choice test (theoretical test) and then on a scenario of cardiac arrest (practical test) before and after exposure to the self-learning methods. The primary endpoint was change in theoretical and practical baseline scores during simulated CPR. This study was conducted in 2017., Results: Both groups improved scores after exposure. The video group had superior performance in both the theoretical test (7.56±0.21 vs 6.51±0.21 for the game group; p = 0.001) and the practical test (9.67±0.21 vs 8.40±0.21 for the game group; p < 0.001). However, students showed a preference for using games, as suggested by the longer time they remained interested in the method (18.57±0.66 min for the game group vs 7.41±0.43 for the video group; p < 0.001)., Conclusions: The self-training modality using a serious game, after a short period of exposure, resulted in inferior students' performance in both theoretical and practical CPR tests compared to the video-based self-training modality. However, students showed a clear preference for using games rather than videos as a form of self-training., Competing Interests: The authors have declared that no competing interests exist.

Background: Striae distensae (SD), an unsightly cutaneous condition characterized by epidermal atrophy, can affect the quality of life of women., Objectives: The aim of our study was to compare the efficacy of a neodymium:yttrium-aluminum-perovskite 1340 nm non-ablative fractional laser (NAFL) and the microneedling (MN) technique to treat striae alba (SA)., Materials and Methods: NAFL and MN were used to treat striae on the longitudinally divided abdominal surface of 20 women classified as Fitzpatrick skin type III or IV (five sessions at monthly intervals). Photographs and skin biopsies were obtained during pretreatment and after the third and fifth treatment sessions for all patients. Patients and two independent evaluators assessed the clinical response using the Global Aesthetic Improvement Scale., Results: Patient-reported evaluation showed improvement of striae using both modalities, with no statistically significant difference between the groups. Collagen and elastic fibers were significantly increased (p < 0.01) after the third and fifth treatment sessions, with no significant difference between the modalities. In addition, Dermatology Life Quality Index scores showed significant improvement (p < 0.001) after the third and fifth treatment sessions compared with pretreatment values, with average values of 8.4 (standard error [SE] ± 1.21), 3.17 (SE ± 0.55), and 2.64 (SE ± 0.60), respectively. The mean pain score using the Visual Analog Scale in the MN group versus the NAFL group was 5.23 (SE ± 0.31) versus 2.39 (SE ± 0.22) [p < 0.001], and the mean duration of adverse events in the NAFL group versus the MN group was 4.03 days (SE ± 0.45) versus 3 days (SE ± 0.37) [p = 0.02]., Conclusion: NAFL and MN are safe for treating SD, particularly in individuals classified as phototype III or IV. MN is a useful non-technology-dependent, low-cost alternative therapy for SA., Clinical Trial Registration Number: NCT03390439.

The development of low-cost transition metal electrocatalysts for the oxygen evolution reaction (OER) has been the focus of intense research. Herein, we report for the first time the synthesis of one dimensional (1D) hollow MFe 2 O 4 (M = Cu, Co and Ni) fibers by the Solution Blow Spinning (SBS) technique and their performance towards OER in alkaline medium. The formation mechanism of the hollow structure and the influence of the fibrillar morphology on the performance of electrocatalysts were discussed. Electrocatalytic performance to generate 10 mA cm -2 with low overpotential followed the sequence: CuFe 2 O 4  > CoFe 2 O 4  > NiFe 2 O 4 . The improved OER performance of hollow CuFe 2 O 4 fibers is due to a superior number of active sites exposed to surface reactions, confirmed by a remarkable electrochemically active surface area (ECSA) of 225 cm 2 . Solution blow spun hollow ferrite fibers showed better electrocatalytic activity towards OER than 1D, 2D and 3D ferrite-based nanostructures reported in the literature., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A new series of 1,4-disubstituted-1,2,3-triazole derivatives were synthesized through the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (Click chemistry) and their inhibitory activities were evaluated against different human glioblastoma (GBM) cell lines, including highly drug-resistant human cell lines GBM02, GBM95. The most effective compounds were 9d, containing the methylenoxy moiety linked to triazole and the tosyl-hydrazone group, and the symmetrical bis-triazole 10a, also containing methylenoxy moiety linked to triazole. Single crystal X-ray diffraction analysis was employed for structural elucidation of compound 9d. In silico analyses of physicochemical, pharmacokinetic, and toxicological properties suggest that compounds 8a, 8b, 8c, 9d, and 10a are potential candidates for central nervous system-acting drugs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease., Methods: Diagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis., Results: Overall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV&#95;max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV&#95;max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%., Conclusions: Our findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis., Trial Registration: The LACOG 0114 study was registered at ClinicalTrials.gov , before study initiation, under identifier NCT02664792.

Objective: to study the expression of the tissue factor (TF) and its correlation with prognosis and survival in patients with gastric carcinoma., Methods: we measured the immunohistochemical expression of TF in 50 specimens of gastric adenocarcinomas from patients submitted to curative surgery. We then compared the intensity of its expression with clinical and pathological data, TNM staging, prognostic factors and survival., Results: all tumors displayed TF expression; the intensity of TF expression was not associated with TNM stage, clinical or pathological variables or general survival., Conclusion: TF has a high expression in gastric carcinoma, but that it is not useful as a prognostic marker.

Polynoncus vazdemelloi Huchet Costa-Silva new species (Coleoptera: Trogidae) from Brazil is described and illustrated with data about the natural history and geographic distribution. Comparative data between P. vazdemelloi, P. juglans (Ratcliffe, 1978), and P. gemmingeri (Harold, 1872), species closely related morphologically, are given. Omorgus (Omorgus) triestinae Pittino, 1987 is removed from synonymy with O. (O.) suberosus (Fabricius, 1775) and reinstated as a valid species.

Pulmonary fibrosis is a specific form of interstitial pneumonia. In addition to the idiopathic cause, it may be caused by drugs such as bleomycin (BLM)-used in the treatment of tumors. Fructose-1,6-bisphosphate (FBP) is a high-energy endogenous glycolytic compound that has antifibrotic, anti-inflammatory, and immunomodulatory effects. The aim of this study was to investigate the effects of FBP on both BLM-induced pulmonary fibrosis in mice and in a human embryonic lung fibroblast (MRC-5) culture system. C57BL/6 mice were divided into four groups: control, FBP, BLM, and BLM plus FBP. A single dose of bleomycin (7.5 U/kg) was administered intratracheally, and survival, body weight, Ashcroft score, and histological analysis were evaluated. Pulmonary function and bronchoalveolar lavage fluid (BALF) were also evaluated after a single dose of bleomycin (1.2 U/kg-intratracheally). Treatment with FBP (500 mg/kg) was given on day 0 intraperitoneally. Fibroblasts (MRC-5 cells) were used to access the effect of FBP in vitro. In vivo, FBP increased the survival rate and reduced body weight loss (BLM vs. BLM plus FBP-p < 0.05). FBP also prevented BLM-induced loss of pulmonary function and decreased BALF inflammatory cells, level of fibrosis, and superficial collagen density (p < 0.05). In vitro, FBP (0.62 and 1.25 mM) had inhibitory activity on MRC-5 cells and was able to induce senescence in fibroblasts. These results showed that FBP has the potential of reducing the toxic effects of BLM and may provide supportive therapy for conventional methods used for the treatment of cancer.

This paper aims to analyse whether time spent in sedentary behaviour was a discriminant criterion for frailty in older adults. This was a cross-sectional study conducted in a sample of 457 elderly individuals aged &ge;60 years. Frailty was defined as the presence of three or more of the following criteria: Unintentional weight loss, low walking speed at a 4.57 m course, reduced manual grip strength, exhaustion and insufficient physical activity level. Participants were classified into two groups: Non-frail or frail. Exposure to sedentary behaviour was assessed by the time spent sitting during a typical week, according to the adapted version of the International Physical Activity Questionnaire. Descriptive (mean, frequency) and inferential statistics (Poisson regression, Pearson&rsquo;s Chi-square, Receiver Operating Characteristic Curve) were used to analyse the data, comparing them to the time-related areas exposed to sedentary behaviour by gender and the presence of fragility. The prevalence of frailty was 22.1% ( n = 101). The most accurate cut-off points of sitting time for predicting frailty were >495 min/day (men) or >536 min/day (women). Time spent in sedentary behaviour can be used to indicate fragility in the elderly of both sexes.

This study investigated the role of kinins and their receptors in malignant brain tumors. As a first approach, GL-261 glioma cells were injected (2 × 10 5 cells in 2 μl/2 min) into the right striatum of adult C57/BL6 wild-type, kinin B 1 and B 2 receptor knockout (KOB 1 R and KOB 2 R) and B 1 and B 2 receptor double knockout mice (KOB 1 B 2 R). The animals received the selective B 1 R (SSR240612) and/or B 2 R (HOE-140) antagonists by intracerebroventricular (i.c.v.) route at 5, 10, and 15 days. The tumor size quantification, mitotic index, western blot analysis, quantitative autoradiography, immunofluorescence, and confocal microscopy were carried out in brain tumor samples, 20 days after tumor induction. Our results revealed an uncontrolled tumor growing in KOB 1 R or SSR240612-treated mice, which was blunted by B 2 R blockade with HOE-140, suggesting a crosstalk between B 1 R and B 2 R in tumor growing. Combined treatment with B 1 R and B 2 R antagonists normalized the upregulation of tumor B 1 R and decreased the tumor size and the mitotic index, as was seen in double KOB 1 B 2 R. The B 1 R was detected on astrocytes in the tumor, indicating a close relationship between this receptor and astroglial cells. Noteworthy, an immunohistochemistry analysis of tumor samples from 16 patients with glioma diagnosis revealed a marked B 1 R immunopositivity in low-grade gliomas or in older glioblastoma individuals. Furthermore, the clinical data revealed a significantly higher immunopositivity for B 1 R, when compared to a lower B 2 R immunolabeling. Taken together, our results show that blocking simultaneously both kinin receptors or alternatively stimulating B 1 R may be of therapeutic value in the treatment of brain glioblastoma growth and malignancy.