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The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines. Cell viability, migration, and clonogenicity were assessed using the following assays MTT, scratch, and colony formation. Antioxidant levels of GSH, as well as activities catalase (CAT), and superoxide dismutase (SOD) were measured. BSO alone exhibited minimal cytotoxic effects, while DOX alone reduced cell viability significantly. The combination of BSO+DOX decreased IC 50 values for most cell lines, demonstrating a synergistic effect, especially in B16/F10, S180, and SVEC4-10 cells. BSO+DOX combination significantly inhibited cell migration and clonogenicity compared to DOX alone. While GSH levels were decreased with BSO+DOX treatment activities of CAT and SOD increased following DOX administration but remained unchanged by BSO. These results suggest that BSO may be considered a valuable tool to improve DOX therapeutic efficacy, particularly in cases of chemotherapy-resistant tumors, as BSO enhances DOX activity while potentially reducing systemic chemotherapeutic drug toxicity.

Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation., (© 2024. The Author(s).)

Bacterial infections pose a significant threat to human health, constituting a major challenge for healthcare systems. Antibiotic resistance is particularly concerning in the context of treating staphylococcal infections. In addressing this challenge, antimicrobial peptides (AMPs), characterized by their hydrophobic and cationic properties, unique mechanism of action, and remarkable bactericidal and immunomodulatory capabilities, emerge as promising alternatives to conventional antibiotics for tackling bacterial multidrug resistance. This study focuses on the Cry10Aa protein as a template for generating AMPs due to its membrane-penetrating ability. Leveraging the Joker algorithm, six peptide variants were derived from α-helix 3 of Cry10Aa, known for its interaction with lipid bilayers. In vitro, antimicrobial assays determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) required for inhibiting the growth of Staphylococcus aureus , Escherichia coli , Acinetobacter baummanii , Enterobacter cloacae , Enterococcus facallis , Klebsiella pneumonia , and Pseudomonas aeruginosa . Time-kill kinetics were performed using the parental peptide AMPCry10Aa, as well as AMPCry10Aa_1 and AMPCry10Aa_5, against E. coli ATCC, S. aureus 111 and S. aureus ATCC strains showing that AMPCry10Aa_1 and AMPCry10Aa_5 peptides can completely reduce the initial bacterial load with less than 2 h of incubation. AMPCry10Aa_1 and AMPCry 10Aa_5 present stability in human serum and activity maintenance up to 37 °C. Cytotoxicity assays, conducted using the MTT method, revealed that all of the tested peptides exhibited cell viability >50% (IC50). The study also encompassed evaluations of the structure and physical-chemical properties. The three-dimensional structures of AMPCry10Aa and AMPCry10Aa_5 were determined through nuclear magnetic resonance (NMR) spectroscopy, indicating the adoption of α-helical segments. Electron paramagnetic resonance (EPR) spectroscopy elucidated the mechanism of action, demonstrating that AMPCry10Aa_5 enters the outer membranes of E. coli and S. aureus , causing substantial increases in lipid fluidity, while AMPCry10Aa slightly increases lipid fluidity in E. coli . In conclusion, the results obtained underscore the potential of Cry10Aa as a source for developing antimicrobial peptides as alternatives to conventional antibiotics, offering a promising avenue in the battle against antibiotic resistance., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.

The effect of calorie restriction, fasting, and ketogenic diets on the treatment of liver cancer remains uncertain. Therefore, we conducted a systematic review to evaluate the effect of restrictive diets on the development and progression of liver cancer in animal models. We did a meta-analysis using the Cochrane Collaboration's Review Manager software, with the random effects model and the inverse variance technique. We examined 19 studies that were conducted between 1983 and 2020. Of these, 63.2% investigated calorie restriction, 21.0% experimented with a ketogenic diet, and 15.8% investigated the effects of fasting. The intervention lasted anything from 48 h to 221 weeks. Results showed that restrictive diets may reduce tumor incidence and progression, with a significant reduction in the risk of liver cancer development. Thereby, our results suggest that putting limits on what you eat may help treat liver cancer in more ways than one., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest that pertain to this work. PROSPERO registration: CRD42021267023., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Buthionine sulfoximine (BSO) is a synthetic amino acid that blocks the biosynthesis of reduced glutathione (GSH), an endogenous antioxidant cellular component present in tumor cells. GSH levels have been associated with tumor cell resistance to chemotherapeutic drugs and platinum compounds. Consequently, by depleting GSH, BSO enhances the cytotoxicity of chemotherapeutic agents in drug-resistant tumors. Therefore, the aim of this study was to conduct a systematic review with meta-analysis of preclinical studies utilizing BSO in cancer treatments. The systematic search was carried out using the following databases: PubMed, Web of Science, Scopus, and EMBASE up until March 20, 2023, in order to collect preclinical studies that evaluated BSO, alone or in association, as a strategy for antineoplastic therapy. One hundred nine investigations were found to assess the cytotoxic potential of BSO alone or in combination with other compounds. Twenty-one of these met the criteria for performing the meta-analysis. The evidence gathered indicated that BSO alone exhibits cytotoxic activity. However, this compound is generally used in combination with other antineoplastic strategies, mainly chemotherapy ones, to improve cytotoxicity to carcinogenic cells and treatment efficacy. Finally, this review provides important considerations regarding BSO use in cancer treatment conditions, which might optimize future studies as a potential adjuvant antineoplastic therapeutic tool.

Optic neuritis (ON) admits diverse differential diagnoses. Petzold proposed diagnostic criteria for ON in 2022, although real-world application of these criteria is missing. We conducted a retrospective review of patients with ON. We classified patients into definite or possible ON, and into groups A (typical neuritis), B (painless), or C (binocular) and estimated the frequency of etiologies for each group. We included 77 patients, with 62% definite and 38% possible ON. CRION and NMOSD-AQP4 negative-ON were less commonly seen in definite ON. Application of the 2022 criteria revealed a lower-than-expected frequency of definite ON, particularly for seronegative non-MS causes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults., Methods: The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish., Results: 1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated., Conclusion: The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Robust evidence have shown diet or dietary components in playing a direct role on cancer chemoprevention such as breast cancer (BC), and also prevention against cancer therapy side effects. In this context, vitamin E isoforms have been associated with tumor suppression pathways, mainly related to proliferation, invasion, metastasis, tumor metabolism and chemoresistance., Objective: Therefore, we performed a systematic review with meta-analysis to assess the effects of vitamin E consumption and/or supplementation on breast cancer risk, treatment, and outcomes., Methods: The studies were selected in the electronic databases PubMed, Science Direct, Scopus and Web of Science., Results: A total of 22 articles were selected, which nine manuscripts we perform the meta-analysis. The summary effect estimate did not indicate any significant association between consumption versus non-consumption of total vitamin E and breast cancer risk. After assessing the effects of vitamin E supplementation on breast cancer risk, only two had data for comparison and vitamin E supplementation presented no impact on breast cancer risk. However, the summary effect estimate from the included studies indicated that vitamin E consumption was inversely associated with breast cancer recurrence in the control group. There are no significant results regarding dietary or supplemental vitamin E intake and BC risk reduction., Conclusion: Finally, regarding recurrence, survival, and mortality, the results indicated that vitamin E consumption was inversely associated with breast cancer recurrence, although no association was found for breast cancer mortality., Competing Interests: Declaration of competing interest The authors declare that there are no conflict of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The diagnosis of irreversible pulpitis (IP) depends on clinical data, especially the chief complaint of the patient, visual inspection, response to the application of stimuli, and radiographic examination. The characterization of nerve fibers (NF) in IP may contribute to better interpret painful symptoms, but has been barely explored. This study sought to characterize the density and integrity of NF in 16 samples of IP and in five healthy pulps (HP) using S-100 and PGP 9.5 markers. Immunohistochemistry was performed to determine the density/mm2 of S-100+ and PGP 9.5+ in NF. The amount of degenerated NF was obtained by subtracting the total NF density from the amount of intact NF. Associations between NF density and integrity and symptomatology were calculated. All samples were positive for S-100 and PGP 9.5. Compared to HP samples (38.20/mm2), IP samples had a lower density of intact NF (6.24/mm2). A significantly higher density of degenerated NF was found in IP samples with spontaneous pain (39.59/mm2) compared to those with provoked pain (23.96/mm2) (p = 0.02). No association was observed between intensity of the inflammatory infiltrate and NF density and integrity (p > 0.05). The findings of this study suggest that pulpitis may involve different stages of degeneration and may be more advanced in cases with spontaneous pain. The symptoms reported by affected individuals do not appear to depend on the intensity of the inflammatory infiltrate, but rather on the integrity of NF.

Background: Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity., Objective: Therefore, this systematic review aimed to evaluate antitumor and chemopreventive activity of different vitamin E isoforms (tocopherols and tocotrienols) through in vitro and in vivo studies., Method: The systematic review was registered in PROSPERO (No. CRD4202126207) and the search was carried out in four electronic databases (PubMed, Science Direct, Scopus and Web of Science) in June 2021 by three independent reviewers. The search equation used was: "Supplementation" AND ("Vitamin E" OR Tocopherol OR Tocotrienol) AND "breast cancer" AND (chemotherapy OR therapy OR prevention). In vitro studies and animal models of breast cancer supplemented with tocopherol or tocotrienol vitamers, alone or in combination, were included., Results: The results revealed 8546 relevant studies that were initially identified in our search. After analysis, a total of 12 studies were eligible for this systematic review. All studies included animal models, and 5 of them also performed in vitro experiments on cancer cell lines. The studies performed supplementation with tocopherols, mixtures (tocopherols and tocotrienols) and synthetic vitamin E forms. There was an significant association of estradiol, dendritic cells and pterostilbene in combined therapy with vitamin E. Vitamin E delayed tumor development, reduced tumor size, proliferation, viability, expression of anti-apoptotic and cell proliferation genes, and upregulated pro-apoptotic genes, tumor suppressor genes and increased immune response. The effects on oxidative stress markers and antioxidant activity were conflicting among studies. Only one study with synthetic vitamin E reported cardiotoxicity, but it did not show vitamin E genotoxicity., Conclusion: In conclusion, vitamin E isoforms, isolated or associated, showed antitumor and chemopreventive activity. However, due to studies heterogeneity, there is a need for further analysis to establish dose, form, supplementation time and breast cancer stage., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Perioperative pain management in small infants weighing <10 kg undergoing liver transplantation is challenging. The use of TEA in this setting has not been reported, as well as its potential role to facilitate IE, ie, in the OR., Methods: We describe here the use of TEA in two small infants who had IE after a LDLT procedure., Results: TEA was successfully performed and IE was achieved in both cases. Postoperative analgesia assessment in the OR was satisfactory according to the FLACC pain scale, with scores of 2 and 3 for each patient, respectively. There were no major complications in the postoperative period, and the two children were discharged home uneventfully., Conclusions: The use of TEA and its influence on IE rate and other perioperative outcomes should be more explored in small infants undergoing LDLT., (© 2022 Wiley Periodicals LLC.)

Introduction: Over the past few years, liver surgery has been in constant evolution and gained many improvements that helped surgeons push limits further. A complex procedure such as left extended trisectionectomy, as described by Makuuchi in 1987, may be performed in selected cases., Aim: Describe a case of successful resection of a huge bilobar liver sarcoma involving all hepatic veins from a young female patient, in which the blood outflow was preserved through an inferior right hepatic vein, leaving only segment 6 as liver remnant. Case Report. A 19-year-old female with a 3-month history of abdominal pain, vomiting, and weight loss was referred for our evaluation. CT scan and MRI revealed a heterogeneous and bulky expansive hepatic lesion, sparing only segment 6, with an estimated volume of 530 cm 3 , corresponding to a 1.2 FLR/BW ratio. The tumor involved the three major hepatic veins, but an inferior right hepatic vein was present, draining the spared segment 6. She was submitted to a left trisectionectomy extended to the caudate lobe and segment 7, including resection of all hepatic veins and lymphadenectomy of the hepatic pedicle. She was discharged on the 7th postoperative day without complications. The histopathological and immunohistochemical analysis demonstrated an undifferentiated embryonal sarcoma of the liver., Conclusion: Inferior right hepatic vein-preserving left extended trisectionectomy is a safe and feasible procedure that should be performed by a hepatobiliary team experienced in major complex hepatectomies., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Reinaldo Fernandes et al.)

Serological databases represent an important source of information to perceive COVID-19 impact on health professionals involved in combating the disease. This paper describes SerumCovid, a COVID-19 serological database focused on the diagnosis of health professionals, providing a preliminary analysis to contribute to the understanding of the antibody response to the SARS-CoV-2. The study population comprises 321 samples from 236 healthcare and frontline workers fighting COVID-19 in Vitória de Santo Antão, Brazil. Samples were collected from at least six days of symptoms to more than 100 days. The used immunoenzymatic assays were Euroimmun Anti-SARS-CoV-2 ELISA IgG and IgA. The most common gender in SerumCovid is female, while the most common age group is between 30 and 39 years old. However, no statistical differences were observed in either genders or age categories. The most reported symptoms were fatigue, headaches, and myalgia. Still, some subjects presented positive results for IgA after 130 days. Based on a temporal analysis, we have not identified general patterns as subjects presented high and low values of IgA and IgG with different evolution trends. Unexpectedly, for subjects with both serological tests, the outcome of IgA and IgG tests were the same (either positive or negative) for more than 80% of the samples. Therefore, SerumCovid helps better understand how COVID-19 affected healthcare and frontline workers, which increases knowledge about the infection and enables direct prevention actions., Competing Interests: The authors have declared that no competing interests exist.

Objective: To identify which functioning, personal and environmental factors are more relevant to adults in hemodialysis treatment., Materials and Methods: Data was collected by semi-structured interview, recorded, transcribed in full, verified and produced by Bardin Thematic content analysis. Two independent researchers identified the relevant themes and named the thematic categories found according to the coding of the International Classification of Functioning, Disability and Health (ICF)., Results: Six men and three women aged between 32-65 years were interviewed, with per capita family income between 1-2.9 minimum salaries and hemodialysis treatment time between 5 to 26 years. Fifty-seven ICF categories were listed: 17 Body Functions, 9 Body Structures, 21 Activities and Participation, and 10 Environmental Factors. Health, transportation and general social support services, systems and policies; doing housework; recreation and leisure; emotional functions, temperament and personality functions; energy and drive functions; sensation of pain; and structures of the cardiovascular system, lower extremity and musculoskeletal structures related to movement were the most reported aspects by the participants., Conclusion: Patients' need for physical/emotional support from their partners, friends and health professionals, including emotional and social support, with health policies, transportation and job maintenance, in order to increase their survival and quality of life.

Objective: The aim of this study was to assess the diaphragm kinetics, respiratory function, and serum dosage of leptin and inflammatory cytokines (IL-6 and TNF-α) in three clinical groups: obese, asthmatic, and healthy., Methods: This is a clinical exploratory study performed on 73 youths (12-24 years of age, 42.5% male) allocated into three groups: obesity (OG, n=33), body mass index (BMIz-score) ≥ +2, asthmatic (AG, n=26) controlled mild asthmatics, classified by GINA, and Healthy Control Group (CG, n=14). The participants were subjected to diaphragmatic ultrasound, spirometry, maximal respiratory pressure, serum leptin levels, and IL-6 and TNF-α whole blood cell culture levels., Results: Diaphragm thickness was higher in OG in comparison to AG and CG (2.0±0.4 vs 1.7±0.5 and 1.6±0.2, both with p<0.05). Maximal voluntary ventilation (MVV) was significantly lower in OG and AG in relation to the CG (82.8±21.4 and 72.5±21.2 vs 102.8±27.3, both with p<0.05). OG has the highest leptin rate among the groups (with the other two groups had p<0.05). All groups had similar TNF-α and IL-6 levels., Conclusion: The muscular hypertrophy found in the diaphragm of the obese individuals can be justified by the increase in respiratory work imposed by the chronic condition of the disease. Such increase in thickness did not occur in controlled mild asthmatics. The IL-6 and TNF-α markers detected no evidence of muscle inflammation, even though leptin was expected to be altered in obese individuals. Both obese and asthmatic patients had lower pulmonary resistance than the healthy ones.

Neurologic complications are being recognized as important outcomes of coronavirus disease 2019 (COVID-19). Pathogenesis is varied and incompletely understood, and may include neuroinvasion, indirect post-infectious neuroinflammation, and cerebrovascular pathologies. We present a case of COVID-19-related encephalomyeloradiculitis with clinical and magnetic resonance imaging characteristics of neuromyelitis optica spectrum disorders that was associated with anti-aquaporin-4 antibodies. Our case suggests post-infectious autoimmunity as a mechanism in at least a subset of patients with COVID-19-related neurologic disease.

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data., (© 2020 The Authors. Ecology © 2020 The Ecological Society of America.)

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data., (© 2020 The Authors. Ecology © 2020 The Ecological Society of America.)

Background: Renal replacement therapy (RRT) is a public health problem worldwide. Kidney transplantation (KT) is the best treatment for elderly patients' longevity and quality of life., Objectives: The primary endpoint was to compare elderly versus younger KT recipients by analyzing the risk covariables involved in worsening renal function, proteinuria, graft loss, and death one year after KT. The secondary endpoint was to create a robot based on logistic regression capable of predicting the likelihood that elderly recipients will develop worse renal function one year after KT., Method: Unicentric retrospective analysis of a cohort was performed with individuals aged ≥60 and <60 years old. We analysed medical records of KT recipients from January to December 2017, with a follow-up time of one year after KT. We used multivariable logistic regression to estimate odds ratios for elderly vs younger recipients, controlled for demographic, clinical, laboratory, data pre- and post-KT, and death., Results: 18 elderly and 100 younger KT recipients were included. Pretransplant immune variables were similar between two groups. No significant differences ( P > 0.05) between groups were observed after KT on laboratory data means and for the prevalences of diabetes mellitus, hypertension, acute rejection, cytomegalovirus, polyomavirus, and urinary infections. One year after KT, the creatinine clearance was higher ( P  = 0.006) in youngers (70.9 ± 25.2 mL/min/1.73 m 2 ) versus elderlies (53.3 ± 21.1 mL/min/1.73 m 2 ). There was no difference in death outcome comparison. Multivariable analysis among covariables predisposing chronic kidney disease epidemiology collaboration (CKD-EPI) equation <60 mL/min/1.73 m 2 presented a statistical significance for age ≥60 years ( P  = 0.01) and reduction in serum haemoglobin ( P  = 0.03). The model presented goodness-fit in the evaluation of artificial intelligence metrics (precision: 90%; sensitivity: 71%; and F 1 score: 0.79)., Conclusion: Renal function in elderly KT recipients was lower than in younger KT recipients. However, patients aged ≥60 years maintained enough renal function to remain off dialysis. Moreover, a learning machine application built a robot (Elderly KTbot) to predict in the elderly populations the likelihood of worse renal function one year after KT., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Ubiracé Fernando Elihimas Júnior et al.)

Gingerol - [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone; [6]-G) - is a phenolic compound with several pharmacological properties. Herein, the aim of the study was to evaluate the toxicogenic effects of [6]-G on Artemia salina nauplii, Allium cepa, HL-60 cell line and Sarcoma 180 (S-180) ascitic fluid cells.For toxic and genotoxic analysis, it was used [6]-G concentrations of 5, 10, 20 and 40 μg mL-1. For cytotoxic evaluation using the MTT test (3- [4,5-dimethyl-thiazol-2-yl] -2,5-diphenyl tetrazolium bromide), serial [6]-G dilutions (1.56-100 μg mL-1) were performed, and S-180, HL-60 and peripheral blood mononuclear cells (PBMC) were treated for 72 h. The IC50 of [6]-G were 1.14, 5.73 and 11.18 μg mL-1 for HL-60, S-180 and PBMC, respectively, indicating a possible selectivity against tumor cell lines. At higher concentrations (>10 μg mL -1 ), toxicity and genotoxicity were observed in the A. cepa test, especially at 40 μg mL -1 . Mechanisms indicating apoptosis, such as toxicity, cytotoxicity and nuclear abnormalities (bridges, fragments, delays, loose chromosomes and micronuclei) suggest that [6]-G has potential for antitumor pharmaceutical formulations., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Xenarthrans-anteaters, sloths, and armadillos-have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data., (© 2019 The Authors. Ecology © 2019 The Ecological Society of America.)

Objective: Despite the high prevalence of rheumatic heart disease in Brazil, the occurrence of functional impairment in children and adolescents with rheumatic heart disease is not clear. The aim of this study was to evaluate exercise tolerance, respiratory muscle strength, lung function, and quality of life of children and adolescents with rheumatic heart disease., Methods: Cross-sectional study, conducted from August to December 2014 with children and adolescents with rheumatic heart disease aged 8 to 16 years. The participants, after completing the socioeconomic, clinical, and quality of life questionnaires were tested by spirometry, manovacuometry and in a 6-minute walk test. The variables and their reference values were compared using the paired Student's t-test. Comparisons between predicted and observed walking distance were done also by Student's t-test, consdiering the categorization of the participants. Correlations between these differences and quantitative variables were assessed by Pearson's coefficient, being significant p<0.05., Results: All 56 participants had a walked distance lower than predicted (p<0.001). The differences between predicted and observed distances were positively correlated with the baseline heart rate (r=0.3545; p=0.007). Expiratory muscle strength was also lower than the predicted values (p<0,001). Regarding quality of life assessment, the mean scores were 70, 77 and 67% for general, physical, and psychosocial aspects, respectively., Conclusions: Children and adolescents with rheumatic heart disease have reduced exercise tolerance, which is related to their higher baseline heart rate; they also show impaired expiratory strength and quality of life.

The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.

The most common subtype of renal cell carcinoma is the clear cell type (ccRCC), accounting for 75 % of cases. Inactivation of VHL gene is thought to be an early event in ccRCC carcinogenesis. Our intention was to assess whether VHL mutational status might provide useful predictive or prognostic information in patients with ccRCC. VHL messenger RNA (mRNA) expression was analyzed by in situ hybridization and its protein by immunohistochemistry on a tissue microarray containing samples from 148 cases. This was validated by qRT-PCR on 62 cases, for which RNA was available. The mutation status was assessed in 91 cases by Sanger sequencing. VHL was found mutated in 57 % of cases, with missense mutations in 26 %, nonsense in 5 %, splice site in 13 %, deletions in 39 %, indels in 8 %, duplications in 8 %, and insertions in 2 % of the cases. The prevalence of mutations by exon was the following: exon 1, 47 %; exon 2, 27 %; and exon 3, 13 %. VHL protein was expressed in a high number of cases (80 %), but significant correlations were not found between protein expression, clinical data, and survival. Importantly, of the 91 samples evaluated by sequencing, 45 were mutated, and 87 % of those were strongly positive. We found 32 novel mutations in the VHL gene in ccRCC. The presence of mutations was not concordant with mRNA or protein expression. Nonsense mutations of the VHL gene appear to be related with poorer prognosis and survival.

The aim is to determine if tumor thickness is a risk factor related to the development of early recurrences in surgically treated oral cavity squamous cell carcinoma (SCC). Retrospective cohort study conducted at Instituto do Câncer do Estado de São Paulo (ICESP). Fifty-seven patients with oral cavity SCC (excluding lip tumors and patients previously submitted to any treatment) were analyzed regarding the occurrence of an early disease progression (locoregional or distant metastasis) within the first 12 months after initial treatment. Tumor thickness and other histological characteristics related to the development of recurrence up to 1 year after treatment were tested. Results demonstrated that tumor thickness greater than 10 mm (P = 0.034), as well as angiolymphatic invasion (P = 0.001), perineural invasion (P = 0.041) and lymph-node metastasis (P = 0.021) was associated with a worse 12-month disease-free survival (Log-Rank test). In multivariate analysis, tumor thickness greater than 10 mm emerged as an independent risk factor for early recurrence in oral cavity tumors (HR = 3.4, 95% CI: 1.005-11.690; P = 0.049--Cox regression). Post-operative radiotherapy seems to be a protective factor for early recurrences in patients with tumor thickness greater than 10 mm (P = 0.017--Log-Rank test; HR = 0.32, 95% CI: 0.12-0.87, P = 0.026--Cox regression). The results of the present research suggest that tumor thickness greater than 10 mm may be an independent adverse factor for early progression of surgically treated oral cavity SCC. Adjuvant therapies, in particular post-operative radiotherapy, should be advocated in this group of patients, regardless of the co-existence of other well-described histological risk factors.

Introduction: The aim of this study was to evaluate the chemical elements composition of root canal filling materials using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX)., Methods: Eighteen standard polyethylene tubes were filled with the following materials: Sealapex(®), Sealer 26(®), MTA Fillapex(®), Pulp Canal Sealer(®), Endofill(®) and AH Plus(®). After 48 hours at 37°C and 95% relative humidity, the samples were surface-sputtered with gold and analyzed using SEM at 5000X magnification. Their chemical composition and element distributionwere determined using EDX. Results were evaluated qualitatively (SEM images and elemental mapping) and quantitatively (weight percentage)., Results: Calcium oxide- and hydroxide-based sealers (Sealapex(®) and Sealer 26(®)) had calcium peaks of 53.58 wt% and 65.00 wt%. MTA Fillapex(®) had 30.58 wt% of calcium and high amounts of silicon (31.02 wt%) and bismuth (27.38 wt%). Zinc oxide- and eugenol-based sealers, Pulp Canal Sealer(®) and Endofill(®), had 67.74 wt% and 63.16 wt% of zinc each. AH Plus(®) had a higher amount of zirconium (64.24 wt%). All materials had elements other than those described by the manufacturers. Surface analysis using EDX revealed that regularity varied, element distribution was uniform, and particles had similar sizes and variable shapes., Conclusions: Most chemical elements were those described by the manufacturers, but percentages were different. The surface of root canal sealers had different regularity findings, uniform distribution and particles of similar sizes but variable shapes.

Background and Purpose: Patients with heart failure disease develop respiratory and functional limitations and suffer from the negative influence on their quality of life. This study was designed to evaluate respiratory muscle strength and its relationship to functional capacity, quality of life and rate of perceived exertion in patients with Chagas cardiomyopathy., Methods: We evaluated 32 patients divided into groups with and without Chagas heart disease. We measured the Minnesota Living with Heart Failure Questionnaire, the maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), distance walked during the 6-minute walk test, rating of perceived exertion (RPE), heart rate, blood pressure, respiratory rate, oxygen saturation and ejection fraction (EF)., Results: The group with Chagas heart disease showed decreased quality of life (overall score: p = 0.001; physical domain: p = 0.002; role-emotional domain: p = 0.031 and general health domain: p < 0.001) and MIP (p < 0.001) when compared with the control group. There was no difference between the distance walked in both groups. The RPE was greater in the group with Chagas heart disease (p = 0.001). The MIP correlated with MEP (r = 0.631, p = 0.009) and EF (r = 0.524, p = 0.037)., Conclusion: The inspiratory muscle strength is reduced, and the decreased quality of life has a negative influence on the physical and emotional aspects of the patients with Chagas cardiomyopathy. No correlation was found between perceived exertion and the reduction of respiratory muscle strength., (Copyright © 2013 John Wiley & Sons, Ltd.)

Little is known on the role played by Neotropical wild carnivores in the Trypanosoma cruzi transmission cycles. We investigated T. cruzi infection in wild carnivores from three sites in Brazil through parasitological and serological tests. The seven carnivore species examined were infected by T. cruzi, but high parasitemias detectable by hemoculture were found only in two Procyonidae species. Genotyping by Mini-exon gene, PCR-RFLP (1f8/Akw21I) and kDNA genomic targets revealed that the raccoon (Procyon cancrivorus) harbored TcI and the coatis (Nasua nasua) harbored TcI, TcII, TcIII-IV and Trypanosoma rangeli, in single and mixed infections, besides four T. cruzi isolates that displayed odd band patterns in the Mini-exon assay. These findings corroborate the coati can be a bioaccumulator of T. cruzi Discrete Typing Units (DTU) and may act as a transmission hub, a connection point joining sylvatic transmission cycles within terrestrial and arboreal mammals and vectors. Also, the odd band patterns observed in coatis' isolates reinforce that T. cruzi diversity might be much higher than currently acknowledged. Additionally, we assembled our data with T. cruzi infection on Neotropical carnivores' literature records to provide a comprehensive analysis of the infection patterns among distinct carnivore species, especially considering their ecological traits and phylogeny. Altogether, fifteen Neotropical carnivore species were found naturally infected by T. cruzi. Species diet was associated with T. cruzi infection rates, supporting the hypothesis that predator-prey links are important mechanisms for T. cruzi maintenance and dispersion in the wild. Distinct T. cruzi infection patterns across carnivore species and study sites were notable. Musteloidea species consistently exhibit high parasitemias in different studies which indicate their high infectivity potential. Mesocarnivores that feed on both invertebrates and mammals, including the coati, a host that can be bioaccumulator of T. cruzi DTU's, seem to take place at the top of the T. cruzi transmission chain.

A survey of the incidence of clinically diagnosed cases of superficial mycosis was carried out using individual report cards in four Family Health units in Patos-PB, in 2007. We had a sample of 197 positive records with Pityriasis and Tinea as the most incident mycoses. There was a higher prevalence among female patients who were between 11 - 20 years of age. A high number of non-identified infections was found: 46,19%. The identification of the agents of such non-identified infections is not possible as they are not infections of compulsory notification.

Objectives: This study attempted to identify which is the more effective suction system. The objective was to compare open versus closed suction systems according to a systematic review., Methods: A search of scientific literature was conducted in MedLine, LILACS and Cochrane between 1997 and August 2007 using the key words: endotracheal suction and closed suction. Included were articles that compared the open and closed suction systems used in adult humans and that were randomized and controlled trials., Results: From the 78 articles identified, only 15 were accepted and described in this review. Nine compared incidence of ventilator-associated pneumonia, six compared oxygen saturation, four compared blood pressure and heart rate, three compared pulmonary volumes, two compared secretion removal and four compared costs. No difference was found in these variables compared: incidence of ventilator associated pneumonia, mortality, intensive care unit length of stay, duration of mechanical ventilation, PaCO2, PaO2, mean blood pressure, heart rate and secretion removal. However, there were always SpO2 and pulmonary volume decreases when using the open suction system; and costs were lower in most of the studies that used the closed suction system., Conclusions: Closed suction system seems to increase the risk of colonization, but has the advantage of not reducing the pulmonary volumes and not entailing a drop of saturation, especially in patients with severe respiratory failure and in the use of higher levels of positive end expiratory pressure.