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JKC Ribeiro, TV Nascimento, AG Agostinho, RM Freitas, LHP Santos, LMQ Machado, JH Leal-Cardoso, MD Moreira-Gomes, VM Ceccatto Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, CE, BrazilCorrespondence: VM CeccattoInstituto de Ciências Biomédicas, Universidade Estadual do Ceará, Av Paranjana, 1700, Fortaleza, Ceará 60740-000, BrazilTel +55 85 3101 9814Fax +55 85 3101 9796Email vania.ceccatto@uece.brBackground: Diabetes mellitus is a syndrome with multiple etiologies involving insulin, in which there is a lack of production and/or loss of sensitivity to this hormone resulting in insulin resistance. Treatment and control of this disease requires changes in diet, use of medication, and lifestyle, such as physical activity. These modifications may compromise quality-of-life if there is no proper guidance for the treatment or alert to possible complications caused by the disease.Methods: This study aimed to evaluate biochemical and hematological parameters, and to assess brain derived neurotrophic factor levels in diabetic Wistar rats submitted to chronic physical exercise.Results: The results demonstrated an increase in plasma concentration of brain-derived neurotrophic factor (BDNF) in association with hyperglycemia reduction in diabetic animals.Discussion: The results obtained suggest that there is a regulation of glucose homeostasis between peripheral tissues and the central nervous system. Exercise-induced BDNF also improved levels of glycemia, body weight, and dyslipidemia. In hematological evaluation, BDNF increase was positively correlated with an improvement in leukocyte parameters. Electrophoresis analyses demonstrated a reduction in levels of pro-inflammatory proteins, lipoprotein fractions, and albumin preservation in diabetic animals trained with elevated concentration of plasma BDNF.Conclusion: In conclusion, this study demonstrated that chronic exercise was able to elevate BDNF levels in plasma, which resulted directly in positive hypoglycemic activity in diabetic animals and a reduction of the metabolic syndrome associated with diabetes mellitus.Keywords: diabetes mellitus, dyslipidemia, exercise, n5-STZ, BDNF

Tatiana Miranda Deliberador, Carlos Stutz, Elisa Sartori, Leandro Kluppel, Rubens Moreno de Freitas Department of Implantology, Master’s Program, Latin American Institute of Dental Research and Education – ILAPEO, Curitiba, PR, BrazilCorrespondence: Tatiana Miranda Deliberador, Department of Implantology, Master’s Program, Latin American Institute of Dental Research and Education – ILAPEO, Rua Jacarezinho 656, Curitiba, PR, 80710-150, Brazil, Email tdeliberador@gmail.comAbstract: Medication-related osteonecrosis of the jaw (MRONJ) can be a debilitating complication that can arise in patients who took or are taking antiresorptive (including bisphosphonates) or antiangiogenic agents, leading to visible bone or a fistula that continues for more than eight weeks, without any history of radiotherapy. This clinical case aimed to describe the treatment of MRONJ with topical active oxygen therapy using blue®m oral gel. A 63-year-old female patient that had been taking weekly sodium alendronate (70 mg) for four years by oral via, presented discomfort and implant movement in the #46 region, by that underwent surgical extraction of the implant. After three months the patient returned and was diagnosed with MRONJ. Initially, conventional therapies were performed, including surgical debridement and antibiotic therapy, but without success. The patient still had clinical signs of osteonecrosis six months after the implant extraction. The entire socket was then filled with blue®m oral gel by topical application. The patient was instructed to continue applying the gel to the region every 8 hours for 15 days. After this period, the patient returned, and it was observed that the wound was in the healing process, with the presence of epithelialized tissue and without bone exposure. The 2-year clinical follow-up showed the lesion had healed entirely, and a new implant was installed. After the osseointegration period, the final prosthesis was placed. The patient remains under clinical follow-up. Therefore, it can be concluded that the application of blue®m oral gel in this clinical case assisted in the recovery of the osteonecrosis lesion.Keywords: osteonecrosis, bisphosphonate, jaw, reactive oxygen species, wound healing, oxygen

Large-scale neuromusculoskeletal models have been used for predicting mechanisms underlying neuromuscular functions in humans. Simulations of such models provide several types of signals of practical interest, such as surface electromyographic signals (EMG), which are compared with experimental data for interpretations of neurophysiological phenomena under study. Specifically, realistic characterization of spectral properties of simulated EMG signals is important for achieving powerful inferences, whereas considerations should be taken for myoelectric signals of different muscles. In this study, we characterized spectral properties of surface interference pattern EMG signals and motor unit action potentials (MUAP) acquired from three plantar flexor muscles: Soleus (SO), Medial Gastrocnemius (MG), and Lateral Gastrocnemius (LG); and one dorsiflexor muscle: Tibialis Anterior (TA). Surface EMG signals were acquired from 20 participants using the same convention for electrode placement. Specifically, interference pattern EMG signals were obtained during isometric constant force contractions at 5%, 10% and 20% of maximum voluntary contraction (MVC), whereas surface MUAPs were decomposed from surface EMG signals obtained at low contraction forces. We compared the spectrum median frequency (MDF) estimated from interference pattern EMG signals across muscles and contraction intensities. Additionally, we compared MDF and durations of MUAPs between muscles. Our results showed that MDF of interference pattern EMG signals acquired from TA were higher compared to SO, MG, and LG for all contraction intensities i.e., 5%, 10%, and 20% MVC. Consistently, MUAPs acquired from TA also had higher MDF values and shorter durations compared to the other leg muscles. We provide herein a dataset with the surface MUAPs waveforms and interference pattern EMG signals obtained for this study, which should be useful for implementing and validating the simulation of myoelectrical signals of leg muscles. Importantly, these results indicate that spectral properties of myoelectrical signals should be considered for improving EMG modeling in large-scale neuromusculoskeletal models., Competing Interests: All authors declare that there are no conflicts of interest related to this work., (Copyright: © 2024 de Freitas, Kohn. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The aim of this study was to evaluate the effect of active oxygen-releasing gel as an adjuvant, with and without antimicrobial photodynamic therapy (aPDT), in the treatment of residual pockets in periodontal patients with type 2 diabetes mellitus (DM2)., Methods: Patients with residual pockets with probing depth (PD) ≥4 mm and bleeding on probing (BOP) were divided into the following groups: SI (n = 17)-subgingival instrumentation in a single session; BM (n = 17)-SI followed by local application of active oxygen-releasing gel inside the periodontal pocket for 3 min; BM + aPDT (n = 17)-SI followed by application of BM for 3 min and pocket irrigation with methylene blue, and 660-nm diode laser irradiation at 100 mW for 50 s. The periodontal clinical parameters, serum levels of glycated hemoglobin, and immunological analysis of crevicular fluid were evaluated. All data were submitted to statistical analysis (α = 5%)., Results: A significant reduction in BOP was verified at 90 and 180 days in the BM + aPDT group. The percentage of sites with PD ≥ 4 mm was significantly reduced at 90 days in BM + aPDT and BM, whereas after 180 days only BM showed a significant reduction. In the BM + aPDT group, there was a significant reduction in tumor necrosis factor α levels at 90 days. There were no differences between the treatments., Conclusion: The use of adjuvant active oxygen-releasing gel, with or without aPDT, resulted in the same clinical benefits as SI in the treatment of residual pockets in poorly controlled DM2 patients., (© 2023 American Academy of Periodontology.)

Objective: Patients with cancer often undergo multiple extended treatments that decrease their quality of life. However, the quality of life of women with breast cancer after they undergo treatment remains underexplored in Brazil. Therefore, this study determined sociodemographic, behavioral, and clinical factors related to the post-treatment quality of life of women with breast cancer., Methods: This cross-sectional study involved 101 women diagnosed with breast cancer between 2014 and 2016 and treated at a Brazilian Oncology Reference Service. Data were collected from them using face-to-face surveys. Quality of life was evaluated using the European Organization for the Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) and EORTC Breast Cancer-specific Quality of Life questionnaire (EORTC QLQ-BR23). The data collected were analyzed using Student's t-test and Mann-Whitney U test., Results: The median score on the global health, functional, and symptom scales of the EORTC QLQ-C30 was 75.00 (Interquartile range=33.33), 75.99 (Standard deviation [SD]=19.26), and 19.67 (SD=16.91), respectively. The mean score on the functional and symptom scales of the EORTC QLQ-BR23 was 61.89 (SD=17.21) and 20.12 (SD=16.94), respectively. Furthermore, higher post-treatment quality of life was found to be associated with being aged 50 or more, being Black, having eight or more years of education, having a partner, having a paying job, receiving treatment from the private healthcare system, having a higher income, living in the municipality where healthcare services are availed, engaging in physical activity, not smoking, being more religious, having more social support, not being overweight, having no comorbidities, and undergoing lumpectomy., Conclusion: Sociodemographic, behavioral, and clinical factors significantly impact the quality of life of women who undergo breast cancer treatment. Implementing interventions that improve health and reducing inequalities in the access to healthcare services can improve the quality of life of these patients., Background: Sociodemographic, clinical, and lifestyle factors impact the quality of life of breast cancer survivors., Background: Breast cancer therapy may affect future perspectives and emotional, cognitive, and sexual function., Background: Some aspects of quality of life still require attention from health professionals., Background: Higher post-treatment quality of life of women with breast cancer is linked to being aged 50 or more, being Black, having 8 or more years of education, having a partner, having a paying job, receiving care from private healthcare, having a high per capita income, residing in the municipality where the service is availed, engaging in physical activity, not smoking, greater religiosity, having more social support, having a normal weight, having no comorbidities, and undergoing lumpectomy.

Objectives: This study aimed to analyze, in the São Paulo state of Brazil, time trends in prevalence, neonatal mortality, and neonatal lethality of central nervous system congenital malformations (CNS-CM) between 2004 and 2015., Methods: Population-based study of all live births with gestational age ≥22 weeks and/or birthweight ≥400 g from mothers living in São Paulo State, during 2004-2015. CNS-CM was defined by the presence of International Classification Disease 10th edition codes Q00-Q07 in the death and/or live birth certificates. CNS-CM was classified as isolated (only Q00-Q07 codes), and non-isolated (with congenital anomalies codes nonrelated to CNS-CM). CNS-CM associated neonatal death was defined as death between 0 and 27 days after birth in infants with CNS-CM. CNS-CM prevalence, neonatal mortality, and lethality rates were calculated, and their annual trends were analyzed by Prais-Winsten Model. The annual percent change (APC) with 95% confidence interval (95%CI) was obtained., Results: 7,237,628 live births were included in the study and CNS-CM were reported in 7526 (0.1%). CNS-CM associated neonatal deaths occurred in 2935 (39.0%). Isolated CNS-CM and non-isolated CNS-CM were found respectively in 5475 and 2051 livebirths, with 1525 (28%) and 1410 (69%) neonatal deaths. CNS-CM prevalence and neonatal lethality were stationary, however neonatal mortality decreased (APC -1.66; 95%CI -3.09 to -0.21) during the study. For isolated CNS-CM, prevalence, neonatal mortality, and lethality decreased over the period. For non-isolated CNS-CM, the prevalence increased, neonatal mortality was stationary, and lethality decreased during the period. The median time of CNS-CM associated neonatal deaths was 18 h after birth., Conclusions: During a 12-year period in São Paulo State, Brazil, neonatal mortality of infants with CNS-CM in general and with isolated CNS-CM showed a decreasing pattern. Nevertheless CNS-CM mortality remained elevated, mostly in the first day after birth.

The COVID-19 disease, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in late 2019 and rapidly spread worldwide, becoming a pandemic that infected millions of people and caused significant deaths. COVID-19 continues to be a major threat, and there is a need to deepen our understanding of the virus and its mechanisms of infection. To study the cellular responses to SARS-CoV-2 infection, we performed an RNA sequencing of infected vs. uninfected Calu-3 cells. Total RNA was extracted from infected (0.5 MOI) and control Calu-3 cells and converted to cDNA. Sequencing was performed, and the obtained reads were quality-analyzed and pre-processed. Differential expression was assessed with the EdgeR package, and functional enrichment was performed in EnrichR for Gene Ontology, KEGG pathways, and WikiPathways. A total of 1040 differentially expressed genes were found in infected vs. uninfected Calu-3 cells, of which 695 were up-regulated and 345 were down-regulated. Functional enrichment analyses revealed the predominant up-regulation of genes related to innate immune response, response to virus, inflammation, cell proliferation, and apoptosis. These transcriptional changes following SARS-CoV-2 infection may reflect a cellular response to the infection and help to elucidate COVID-19 pathogenesis, in addition to revealing potential biomarkers and drug targets.

Although biofloc technology is already recognized as advantageous and practical for aquaculture for the effects of maintaining water quality and improving the health status and resistance of cultivated animals against pathogens, little is known about the way of action involved. This study aimed to evaluate the performance of bacterial groups as inducers in the formation of flocs compared to a system with spontaneous formation. Therefore, three microsystems were built in 3L tanks with constant aeration to induce the biofloc aggregation with addition of bacterial consortiuns with differentiated functions. It was used a control, without addition of bacterial consortium; B1 with addition of probiotic bacteria consortium; and B2, with adding nitrifying bacteria consortium. During the experimental period were evaluated physicochemical variables and quantifications of bacterial cultivable groups: Heterotrophic Bacteria and Vibrio. Also was the microscopic characterization of the flakes and tests of antimicrobial activity against pathogenic bacteria. Systems B1 and B2 showed promising results in relation to control (spontaneous bioflocs), showing more homogeneous flake formation, antimicrobial activity against the tested pathogens and greater biological diversity in the systems. The bacteria used in these tests were able to optimize the formation of microbial aggregates, showing potential for application in cultivation systems, in order to obtain improvements in productivity.

Background: In high- and middle-income countries, mortality associated to congenital diaphragmatic hernia (CDH) is high and variable. In Brazil, data is scarce regarding the prevalence, mortality, and lethality of CDH. This study aimed to analyze, in São Paulo state of Brazil, the temporal trends of prevalence, neonatal mortality and lethality of CDH and identify the time to CDH-associated neonatal death., Methods: Population-based study of all live births with gestational age ≥ 22 weeks, birthweight ≥400g, from mothers residing in São Paulo State, Brazil, during 2004-2015. CDH definition and its subgroups classification were based on ICD-10 codes reported in the death and/or live birth certificates. CDH-associated neonatal death was defined as death up to 27 days after birth of infants with CDH. CDH prevalence, neonatal mortality and lethality were calculated and their annual percent change (APC) with 95% confidence intervals (95%CI) was analyzed by Prais-Winsten. Kaplan-Meier estimator identified the time after birth that CDH-associated neonatal death occurred., Results: CDH prevalence was 1.67 per 10,000 live births, with a significant increase throughout the period (APC 2.55; 95%CI 1.30 to 3.83). CDH neonatal mortality also increased over the time (APC 2.09; 95%CI 0.27 to 3.94), while the lethality was 78.78% and remained stationary. For isolated CDH, CDH associated to non-chromosomal anomalies and CDH associated to chromosomal anomalies the lethality was, respectively, 72.25%, 91.06% and 97.96%, during the study period. For CDH as a whole and for all subgroups, 50% of deaths occurred within the first day after birth., Conclusions: During a 12-year period in São Paulo State, Brazil, CDH prevalence and neonatal mortality showed a significant increase, while lethality remained stable, yet very high, compared to rates reported in high income countries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Scavacini Marinonio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Through structural equation modeling (SEM), this study aimed to evaluate the influence of commensality under the dietary pattern of Brazilian adolescents based on data from the third edition of the National Survey of School Health (PeNSE), conducted in 2015. PeNSE is a cross-sectional survey with a complex probabilistic sampling plan and with representativeness for adolescents in public and private schools in Brazil. Based on recommendations from the Food Guide for the Brazilian Population (Guia Alimentar Para a População Brasileira), we developed a theoretical model, using the SEM model, (stratified by sex) to investigate the relationship between sociodemographic characteristics, handwashing, body satisfaction, and commensality, and their influence on the eating pattern of adolescents. For males, age significantly and inversely proportionally associated with commensal practice (SDE: -0.28, p<0.01). Regarding female subjects, body dissatisfaction was shown to be negatively associated with commensality to a more significant effect when compared to males (SDE: -0.30, p<0.01). On the other hand, commensality positively associated with healthy eating patterns for males (SDE: 0.42, p<0.01) and females (SDE: 0.62, p<0.01). Through the analyses conducted in this study, a positive relationship between commensality and the Healthy Eating Pattern of Brazilian adolescents was observed. There were also different influences for each sex., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Cervical transcutaneous spinal cord stimulation (tSCS) is a rehabilitation tool which has been used to promote upper-limb motor recovery after spinal cord injury. Importantly, optimizing sensory fiber activation at specific spinal segments could enable activity-dependent neuromodulation during rehabilitation., Methods: An anatomically realistic cervical tSCS computational model was used to analyze the activation of α-motor and Aα-sensory fibers at C7 and C8 spinal segments using nine cathode electrode configurations. Specifically, the cathode was simulated at three vertebral level positions: C6, C7, and T1; and in three sizes: 5.0 × 5.0, 3.5 × 3.5, and 2.5 × 2.5 cm 2 , while the anode was on the anterior neck. Finite element method was used to estimate the electric potential distribution along α-motor and Aα-sensory fibers, and computational models were applied to simulate the fiber membrane dynamics during tSCS. The minimum stimulation intensity necessary to activate the fibers (activation threshold) was estimated and compared across cathode configurations in an effort to optimize sensory fiber activation., Results: Our results showed that nerve fibers at both C7 and C8 spinal segments were recruited at lower stimulation intensities when the cathode was positioned over the C7 or T1 vertebra compared with the C6 position. Sensory fibers were activated at lower stimulation intensities using smaller electrodes, which could also affect the degree of nerve fiber activation across different positions. Importantly, Aα-sensory fibers were consistently recruited before α-motor fibers., Conclusions: These results imply that cathode positioning could help optimize preferential activation of hand muscles during cervical tSCS., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

The turnover of microbial communities across space is dictated by local and regional factors. Locally, selection shapes community assembly through biological interactions between organisms and the environment, while regional factors influence microbial dispersion patterns. Methods used to disentangle the effects of local and regional factors typically do not aim to identify ecological processes underlying the turnover. In this paper, we identified and quantified these processes for three operational microbial subcommunities (cyanobacteria, particle-attached, and free-living bacteria) from a tropical cascade of freshwater reservoirs with decreasing productivity, over two markedly different dry and rainy seasons. We hypothesized that during the dry season communities would mainly be controlled by selection shaped by the higher environmental heterogeneity that results from low hydrological flow and connectivity between reservoirs. We expected highly similar communities shaped by dispersal and a more homogenized environment during the rainy season, enhanced by increased flow rates. Even if metacommunities were largely controlled by regional events in both periods, the selection had more influence on free-living communities during the dry period, possibly related to elevated dissolved organic carbon concentration, while drift as a purely stochastic factor, had more influence on cyanobacterial communities. Each subcommunity had distinct patterns of turnover along the cascade related to diversity (Cyanobacteria), lifestyle and size (Free-living), and spatial dynamics (particle-attached)., 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 © 2022 Vieira, Bagatini, de Moraes, Freitas, Sarmento, Bertilsson and Vieira.)

Objective:  The study aimed to characterize the clinical, histological, and immunohistochemical profile of women with invasive breast cancer, according to the risk for Hereditary Predisposition Breast and Ovarian Cancer Syndrome in a Brazilian population., Methods:  This is a retrospective study performed from a hospital-based cohort of 522 women, diagnosed with breast cancer treated at an oncology referral center in the Southeast region of Brazil, between 2014 and 2016., Results:  Among the 430 women diagnosed with invasive breast cancer who composed the study population, 127 (29.5%) were classified as at increased risk for hereditary predisposition to breast and ovarian cancer syndrome. There was a lower level of education in patients at increased risk (34.6%) when compared with those at usual risk (46.0%). Regarding tumor characteristics, women at increased risk had higher percentages of the disease diagnosed at an advanced stage (32.3%), and with tumors > 2cm (63.0%), with increased prevalence for both characteristics, when compared with those at usual risk. Furthermore, we found higher percentages of HG3 (43.3%) and K i -67 ≥ 25% (64.6%) in women at increased risk, with prevalence being about twice as high in this group. The presence of triple-negative tumors was observed as 25.2% in women at increased risk and 6.0% in women at usual risk, with the prevalence of absence of biomarkers being 2.5 times higher among women in the increased risk group., Conclusion:  From the clinical criteria routinely used in the diagnosis of breast cancer, the care practice of genetic counseling for patients at increased risk of hereditary breast cancer in contexts such as Brazil is still scarce., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Introduction: The hydration status is a predictor of survival in critically ill patients. However, it is unclear whether this association depends on the patient clinical condition. This study was designed to analyze the impact of hydration status on survival of critically ill patients with acute kidney injury (AKI) with or without sepsis., Methods: A prospective cohort study following critically ill patients with AKI consecutively admitted over a one-year period to a teaching hospital intensive care unit (ICU). All patients with AKI stage three or higher of the KDIGO score were included. The hydration status was evaluated through the overhydration (OH) parameter of spectroscopy bioimpedance and sepsis was defined according Sepse-3 criteria. The survival analysis used adjusted competing-risks regression., Results: Forty-eight patients were included, 27 (56%) with a sepsis diagnosis. The main negative predictors of survival among sepsis patients, adjusted by SAPS3 score, were higher OH (SHR 1.1, 95% CI 1.0-1.2, p = 0.02), mechanical ventilation (SHR 6.9, 95% CI 1.0-47.8, p = 0.04) and older age (SHR 1.1, 95% CI 1.0-1.1, p = 0.005). The predictors in non-sepsis patients were lower OH (SHR 0.82, 95% CI 0.71-0.95, p = 0.008) and mechanical ventilation (SHR 12, 95% CI 2.4-6.6, p < 0.001)., Conclusions: This finding suggests that extracellular overhydration is an independent predictor of survival in critically ill patients with sepsis, but it seems to have opposite effect in non-sepsis patients., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objective . Cervical transcutaneous spinal cord stimulation (tSCS) is a promising technology that can support motor function recovery of upper-limbs after spinal cord injury. Its efficacy may depend on the ability to recruit sensory afferents, conveying excitatory inputs onto motoneurons. Therefore, understanding its physiological mechanisms is critical to accelerate its development towards clinical applications. In this study, we used an anatomically realistic cervical tSCS computational model to compare α-motor, Aα-sensory, and Aβ-sensory fiber activation thresholds and activation sites. Approach . We developed a 3D geometry of the cervical body and tSCS electrodes with a cathode centred at the C7 spinous process and an anode placed over the anterior neck. The geometrical model was used to estimate the electric potential distributions along motor and sensory fiber trajectories at the C7 spinal level using a finite element method. We implemented dedicated motor and sensory fiber models to simulate the α-motor and Aα-sensory fibers using 12, 16, and 20 µm diameter fibers, and Aβ-sensory fibers using 6, 9, and 12 µm diameter fibers. We estimated nerve fiber activation thresholds and sites for a 2 ms monophasic stimulating pulse and compared them across the fiber groups. Main results . Our results showed lower activation thresholds of Aα- and Aβ-sensory fibers compared with α-motor fibers, suggesting preferential sensory fiber activation. We also found no differences between activation thresholds of Aα-sensory and large Aβ-sensory fibers, implying their co-activation. The activation sites were located at the dorsal and ventral root levels. Significance . Using a realistic computational model, we demonstrated preferential activation of dorsal root Aα- and Aβ-sensory fibers compared with ventral root α-motor fibers during cervical tSCS. These findings suggest high proprioceptive and cutaneous contributions to neural activations during cervical tSCS, which inform the underlying mechanisms of upper-limb functional motor recovery., (Creative Commons Attribution license.)

microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.

Arbovirus epidemiology lacks efficient and timely surveillance systems with accurate outbreak alert signals. We devised a citywide integrated surveillance system combining entomologic, epidemiologic, and entomo-virologic data gathered during 2017-2020 in Foz do Iguaçu, Brazil. We installed 3,476 adult mosquito traps across the city and inspected traps every 2 months. We compared 5 entomologic indices: traditional house and Breteau indices for larval surveys and trap positivity, adult density, and mosquitoes per inhabitant indices for adult trapping. We screened for dengue, Zika, and chikungunya viruses in live adult Aedes aegypti mosquitoes collected from traps. Indices based on adult mosquito sampling had higher outbreak predictive values than larval indices, and we were able to build choropleth maps of infestation levels <36 h after each round of trap inspection. Locating naturally infected vectors provides a timely support tool for local public health managers to prioritize areas for intervention response to prevent virus outbreaks.

Introduction : The Activities-specific Balance Confidence scale is the most used tool to quantify balance confidence, a psychological factor related to balance impairment among older adults. Objective : To investigate the validity and reliability of the original and short versions of the Brazilian Activities-specific Balance Confidence scales, to determine cutoff points for balance impairments and to identify the determinants of balance confidence of community-dwelling older adults. Methods : The validity of both versions of the scales was verified by correlating its results with postural balance, fear of falling and mobility (n = 105). Both scales were administered with a 30 min (interrater reliability, n = 158) and 1-week intervals (intrarater reliability, n = 105). Receiver operating characteristic curve was used to determine the cutoff points, and linear regression was applied to identify the determinants of balance confidence. Results : The Brazilian versions of the scale correlated to postural balance, fear of falling and mobility ( p < .05). Excellent interrater (α = 0.946, 95% CI: 0.902-0.976; α = 0.932, 95% CI: 0.918-0.960) and intrarater reliability (α = 0.946, 95% CI: 0.905-0.960; α = 0.952, 95% CI: 0.921-0.965) were found for the original and short versions.  Values of ≤67% (sensitivity: 81%, specificity: 77.4%) and ≤44% (sensitivity: 87.5%, specificity: 82.1%) were observed to identify balance impairments for the original and short versions of the scale. Physical inactivity, fear of falling, imbalance sensation, and number of falls are the main determinants of balance confidence. Conclusion : Both scales are valid and reliable to assess balance confidence. Cutoff points to identify balance impairments were determined and some factors may act as possible predictors of balance confidence.

Cervical transcutaneous spinal cord stimulation (tSCS) has been utilized in applications for improving upper-limb sensory and motor function in patients with spinal cord injury. Although therapeutic effects of continuous cervical tSCS interventions have been reported, neurophysiological mechanisms remain largely unexplored. Specifically, it is not clear whether sub-threshold intensity and 10-min duration continuous cervical tSCS intervention can affect the central nervous system excitability. Therefore, the purpose of this study was to investigate effects of sub-motor-threshold 10-min continuous cervical tSCS applied at rest on the corticospinal and spinal reflex circuit in ten able-bodied individuals. Neurophysiological assessments were conducted to investigate (1) corticospinal excitability via transcranial magnetic stimulation applied on the primary motor cortex to evoke motor-evoked potentials (MEPs) and (2) spinal reflex excitability via single-pulse tSCS applied at the cervical level to evoke posterior root muscle (PRM) reflexes. Measurements were recorded from multiple upper-limb muscles before, during, and after the intervention. Our results showed that low-intensity and short-duration continuous cervical tSCS intervention applied at rest did not significantly affect corticospinal and spinal reflex excitability. The stimulation duration and/or intensity, as well as other stimulating parameters selection, may therefore be critical for inducing neuromodulatory effects during cervical tSCS.

Cervical transcutaneous spinal cord stimulation (tSCS) efficacy for rehabilitation of upper-limb motor function was suggested to depend on recruitment of Ia afferents. However, selectivity and excitability of motor activation with different electrode configurations remain unclear. In this study, activation of upper-limb motor pools was examined with different cathode and anode configurations during cervical tSCS in 10 able-bodied individuals. Muscle responses were measured from six upper-limb muscles simultaneously. First, postactivation depression was confirmed with tSCS paired pulses (50-ms interval) for each cathode configuration (C6, C7, and T1 vertebral levels), with anode on the anterior neck. Selectivity and excitability of activation of the upper-limb motor pools were examined by comparing the recruitment curves (10-100 mA) of first evoked responses across muscles and cathode configurations. Our results showed that hand muscles were preferentially activated when the cathode was placed over T1 compared with the other vertebral levels, whereas there was no selectivity for proximal arm muscles. Furthermore, higher stimulation intensities were required to activate distal hand muscles than proximal arm muscles, suggesting different excitability thresholds between muscles. In a separate protocol, responses were compared between anode configurations (anterior neck, shoulders, iliac crests, and back), with one selected cathode configuration. The level of discomfort was also assessed. Largest muscle responses were elicited with the anode configuration over the anterior neck, whereas there were no differences in the discomfort. Our results therefore inform methodological considerations for electrode configuration to help optimize recruitment of Ia afferents during cervical tSCS. NEW & NOTEWORTHY We examined selectivity and excitability of motor activation in multiple upper-limb muscles during cervical transcutaneous spinal cord stimulation with different cathode and anode configurations. Hand muscles were more activated when the cathode was configured over the T1 vertebra compared with C6 and C7 locations. Higher stimulation intensities were required to activate distal hand muscles than proximal arm muscles. Finally, configuration of anode over anterior neck elicited larger responses compared with other configurations.

There is a growing environmental concern in the world for replacing the traditional petroleum-based products. The aim of this work was to evaluate the structure - property relationship of banana peel lignins (BPLs) as antioxidant and antimicrobial agents by controlling the parameters of organosolv process. The milled banana peel was hydrolyzed using an aqueous acetic acid solution (70, 80 and 90% v/v) and 2.0% v/v HCl at 110 °C for 1, 2 and 3 h. BPLs were characterized by FTIR, 1 H NMR, 1 H 13 C HSQC, 31 P NMR, GPC and TGA. The antioxidant capacity of BPLs was evaluated by DPPH, ABTS and H 2 O 2 assays, comparing their performance with that of ascorbic and gallic acid. The antimicrobial activity of BPLs was evaluated against E. coli. The reaction time and acetic acid/water ratio had significant effects on the yield and purity of BPLs. The composition of organosolv solution also affected their total amount of hydroxyls (0.71-0.82 mmol g -1 ), M w (2759-3954 g mol -1 ), T onset (232-254 °C), antioxidant and antimicrobial activities. It can be concluded that the control of organosolv parameters can be a useful tool for tuning the structural features of lignins and to maximize their performance., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Physical exercise is a health promotion factor regulating gene expression and causing changes in phenotype, varying according to exercise type and intensity. Acute strenuous exercise in sedentary individuals appears to induce different transcriptional networks in response to stress caused by exercise. The objective of this research was to investigate the transcriptional profile of strenuous experimental exercise., Methodology: RNA-Seq was performed with Rattus norvegicus soleus muscle, submitted to strenuous physical exercise on a treadmill with an initial velocity of 0.5 km/h and increments of 0.2 km/h at every 3 min until animal exhaustion. Twenty four hours post-physical exercise, RNA-seq protocols were performed with coverage of 30 million reads per sample, 100 pb read length, paired-end, with a list of counts totaling 12816 genes., Results: Eighty differentially expressed genes (61 down-regulated and 19 up-regulated) were obtained. Reactome and KEGG database searches revealed the most significant pathways, for down-regulated gene set, were: PI3K-Akt signaling pathway, RAF-MAP kinase, P2Y receptors and Signaling by Erbb2. Results suggest PI3K-AKT pathway inactivation by Hbegf, Fgf1 and Fgr3 receptor regulation, leading to inhibition of cell proliferation and increased apoptosis. Cell signaling transcription networks were found in transcriptome. Results suggest some metabolic pathways which indicate the conditioning situation of strenuous exercise induced genes encoding apoptotic and autophagy factors, indicating cellular stress., Conclusion: Down-regulated networks showed cell transduction and signaling pathways, with possible inhibition of cellular proliferation and cell degeneration. These findings reveal transitory and dynamic process in cell signaling transcription networks in skeletal muscle after acute strenuous exercise., Competing Interests: The authors declare there are no competing interests., (©2021 Felipe et al.)

Background: Population-based studies analyzing neonatal deaths in middle-income countries may contribute to design interventions to achieve the Sustainable Development Goals, established by United Nations. This study goal is to analyze the annual trend of neonatal mortality in São Paulo State, Brazil, over a 10-year period and its underlying causes and to identify maternal and neonatal characteristics at birth associated with neonatal mortality., Method: A population-based study of births and deaths from 0 to 27 days between 2004 and 2013 in São Paulo State, Brazil, was performed. The annual trend of neonatal mortality rate according to gestational age was analyzed by Poisson or by Negative Binomial Regression models. Basic causes of neonatal death were classified according to ICD-10. Association of maternal demographic variables (block 1), prenatal and delivery care variables (block 2), and neonatal characteristics at birth (block 3) with neonatal mortality was evaluated by Poisson regression analysis adjusted by year of birth., Results: Among 6,056,883 live births in São Paulo State during the study period, 48,309 died from 0 to 27 days (neonatal mortality rate: 8.0/1,000 live births). For the whole group and for infants with gestational age 22-27, 28-31, 32-36, 37-41 and ≥ 42 weeks, reduction of neonatal mortality rate was, respectively, 18 %, 15 %, 38 %, 53 %, 31 %, and 58 %. Median time until 50 % of deaths occurred was 3 days. Main basic causes of death were respiratory disorders (25 %), malformations (20 %), infections (17 %), and perinatal asphyxia (7 %). Variables independently associated with neonatal deaths were maternal schooling, prenatal care, parity, newborn sex, 1st minute Apgar, and malformations. Cesarean delivery, compared to vaginal, was protective against neonatal mortality for infants at 22-31 weeks, but it was a risk factor for those with 32-41 weeks., Conclusions: Despite the significant decrease in neonatal mortality rate over the 10-year period in São Paulo State, improved access to qualified health care is needed in order to avoid preventable neonatal deaths and increase survival of infants that need more complex levels of assistance.

Purpose: The aim of this study was to compare the deviation of the implant position after placement in single maxillary incisor post-extraction sockets between fully and partially guided surgery., Materials and Methods: Twenty-four patients with a failing maxillary incisor were randomly allocated into two groups: the partially guided surgery (PGS, n = 12) group or fully guided surgery (FGS, n = 12) group. Clinical analyses, intra-oral scans, and computed tomography scans (CT) were initially performed to define the virtual positioning of the implants and fabrication of the 3D printed surgical guides. A narrow, 3.5 × 16 mm implant was placed in each socket. In this moment, the insertion torque (IT) was assessed and resonance frequency analysis (RFA) was performed. All patients received an immediate provisional without occlusal contacts. Another CT scan was performed after the procedures to compare the implant position with the virtually planned position., Results: Significant deviations occurred at the implant apex, according to the global and facial-palatal analyses, in comparison to its cervical position. The PGS group also presented a larger deviation in the MD position. No statistical differences between the groups were detected, however, there was a tendency of lower angular deviation in the PGS group., Conclusions: While there was a slight deviation from the virtually planned position of the implant to the actual position and a tendency of lower angular deviation in the PGS group, there was no difference among groups regarding its position and primary stability. (UNT: 1111-1214-2812 - http://www.ensaiosclinicos.gov.br/rg/RBR-4tmcrk/)., (© 2020 Wiley Periodicals LLC.)

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score ≥ 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0-4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score > 2), while 62.5% demonstrated a weak or absent protein expression (score ≤ 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion ( p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 ( p = 0.011)] and a high Ki67 index ( p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26-3.66; p = 0.005) in all patients ( n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09-4.06; p = 0.027) in patients with localized disease at diagnosis ( n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.

This study evaluated the impact of soft tissue grafts to reduce marginal peri-implant recession (MPR) after 1 year of follow-up. A total of 24 patients with one single failing maxillary incisor presenting facial bone dehiscence and receiving an immediate implant, bone graft, and provisional were randomly divided into three groups (n = 8 in each group): control (CTL), collagen matrix (CM), and connective tissue graft (CTG). Clinical, photographic, and tomographic analyses were performed to evaluate tissue alterations. The use of a CTG avoided MPR (P < .05) and provided better contour of the alveolar ridge (P < .01) and greater thickness (P < .05) of the soft tissue at the implant facial aspect.

Purpose: The objective of this systematic review was to assess the three-dimensional changes in bone tissue after immediate installation of a single implant in a fresh extraction socket in the anterior maxilla., Methods: After defining a strategy, an electronic search was carried out using the databases PubMed, Embase, LILACS, Web of Science, Cochrane, and Scopus. In addition, the gray literature was also researched using Google Scholar and ProQuest. Two reviewers independently screened for eligible studies, assessed the methodological quality, and extracted the data. The inclusion criteria were observational studies and experimental studies that assessed bone response after the immediate installation of a single implant in a fresh extraction socket, immediately loaded or not, in the region between the maxillary canines. Studies were included in any language, with no publication date restrictions and with a minimum of 6 months of follow-up after the surgical procedure., Results: From a total of 3272 articles, only 12 studies met the inclusion criteria and were selected for the review. Bone remodeling after immediate installation of a dental implant was assessed using standardized periapical radiographs and cone beam computed tomography (CBCT)., Conclusion: It can be concluded that bone remodeling occurs after tooth extraction and immediate implant installation.

The aim of this research letter was to report the results of a pilot study designed to compare the real and virtual position of implants placed using computer-guided flapless implant surgery for single restorations in the premaxilla. A total of 8 patients (2 men and 6 women) with a mean age of 40 years old (range: 32-73 years) had a total of 11 implants inserted using a tooth-supported stereolithographic guide. After implant placement, the positions (coronal, central, and apical) and angulation of the implants installed in relation to those planned were determined via the superposition of pre- and postoperative 3-dimensional models using Dental Slice software (Bioparts, Brasília, Brazil). The mean angular deviation was 2.54° ± 0.71°. The deviations found for the coronal, central, and apical positions were 1.3 ± 0.77 mm, 1.49 ± 0.58 mm, and 2.13 ± 1.32 mm, respectively.

Olanzapine (OLZ), is used in the treatment of bipolar disorder and schizophrenia, diseases that present oxidative stress in their physiopathology. It has low aqueous solubility, which may lead to low oral bioavailability. The search of new drug delivery systems (DDSs) that may increase dissolution rate of OLZ, associated with the investigation of the antioxidant potential of the loaded-systems become of major importance to understand improvement in bipolar disorder and schizophrenia therapy. Thus, this study aimed to evaluate the in vitro antioxidant potential of two different Layered Double Hydroxides (LDH) loaded with 5% of OLZ (CaAl and NiAl), by radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl and nitric oxid); radical cation scavenging activity (2,2'-azino-bis3-ethylbenzthiazoline-6-sulfonic acid ABTS) and evaluation of inhibition capacity of lipid peroxidation by thiobarbituric acid (TBARS). The results showed that both obtained LDH systems presented in vitro antioxidant capacity when associated with OLZ in all methods performed, and this activity is more pronounced with the systems containing OLZ compared to pure drug. The systems with CaAl was shown to have increased antioxidant potential, compared to NiAl, increasing the antioxidant activity up to 40,83%, 15,84% and 16,73%, as showed by the DPPH, nitric oxide and TBARS tests, respectively. The results revealed that the use of LDHs as a functional excipient may be promising in the pharmaceutical industry for bipolar disorder and schizophrenia therapy., (Copyright © 2018. Published by Elsevier Inc.)

Background: Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support significant bone formation when used to augment the maxillary sinus for implant dentistry. Nevertheless, bone biomaterials have been suggested to extend rhBMP-2/ACS with limited support of the merits of such approaches., Objectives: To evaluate local bone formation/dental implant osseointegration following implantation of rhBMP-2/ACS combined with a ceramic bone biomaterial using a mini-pig sinus augmentation model., Methods: Twelve adult Göttingen mini-pigs received rhBMP-2/ACS (rhBMP-2 adjusted to 0.43 mg/cc) alone or combined with an off-the-shelf biphasic ceramic (15%/85% HA/ß-TCP) biomaterial at 3:1, 1:1 and 1:3 ratios randomized to contra-lateral maxillary sinus sites yielding rhBMP-2/ACS fractions of 100%, 75%, 50% and 25%, respectively. A 4-cc implant volume was used for all sites. Two threaded dental implants (ø4.0 × 11.5 mm) were placed at each site. The animals were euthanized at 8 weeks for histologic analysis., Results: Surgical execution and healing were generally uneventful, infraorbital local swelling was observed in all animals until suture removal. rhBMP-2/ACS combined with the ceramic biomaterial did not significantly enhance local bone formation (range 9.0 ± 1.5 to 9.7 ± 2.1 mm) compared with rhBMP-2/ACS alone (8.6 ± 1.1 mm; p > 0.05). Variations in rhBMP-2/ACS to ceramic matrix ratios yielding rhBMP-2 doses approximating 0.4, 0.9, 1.3 and 1.7 mg/sinus did not appreciably influence bone formation/osseointegration., Conclusions: Whereas rhBMP-2/ACS supports significant bone formation/osseointegration in the mini-pig sinus augmentation model and thus appears an effective alternative for sinus augmentation procedures, adding a ceramic biomaterial to rhBMP-2/ACS does not produce meaningful biological advantages., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Several mutations in voltage gated sodium channel (Na V ) have been identified in Aedes aegypti populations worldwide. However, only few are related to knockdown resistance to pyrethroids, most of which with variations in the 1016 and 1534 Na V sites. In Brazil, at least two Na V alleles are known: Na V R1, with a substitution in the 1534 (1016 Val + + 1534 Ile kdr ) and Na V R2, with substitutions in both 1016 and sites (1016Ile kdr + 1534Cys kdr ). There is also the duplication in the Na V gene, with one copy carrying the substitution Ile1011Met, although its effects on pyrethroid resistance remain to be clarified. Our goals in this study were (1) to determine the role of each kdr Na V allele and the duplication on pyrethroid resistance and (2) to screen the frequency of the kdr alleles in 27 several natural Ae. aegypti populations from the metropolitan region of Rio de Janeiro., Methods: Pyrethroid resistance was evaluated by a knockdown time ( Kd T) assay, an adaptation of the WHO test tubes with paper impregnated with deltamethrin. We used laboratory-selected Ae. aegypti lineages: R1R1 and R2R2 (homozygous for the kdr Na V R1 and Na V R2 alleles, respectively), Dup (with duplication in the Na V gene), Rockefeller (the susceptibility reference control), and F1 hybrids among them. Genotyping of both 1016 and 1534 Na V sites was performed in 811 Ae. aegypti sampled from 27 localities from Rio de Janeiro (17), Niterói (6) and Nova Iguaçu (4) cities, Rio de Janeiro State, Brazil, with a TaqMan real time PCR approach., Results: The laboratory lineages R1R1, R2R2, and R1R2 were the only ones that needed more than 60 minutes to knock down all the insects exposed to the pyrethroid, being the Kd T R2R2 > R1R2 > R1R1, corroborating the recessive nature of the kdr mutations. Frequency of kdr alleles Na V R1 and Na V R2 in field-caught mosquitoes varied from 0 to 52% and 43 to 86%, respectively, evidencing high levels of "resistant genotypes" (R1R1, R1R2, and R2R2), which together summed 60 to 100% in Ae. aegypti populations from Rio de Janeiro., Conclusions: The Na V R1 and Na V R2 kdr alleles confer resistance to the pyrethroid deltamethrin in homozygotes and R1R2 heterozygotes, being the R2R2 most resistant genotype. The allele containing duplication in the Na V gene, with a mutation in the 1011 site, did not confer resistance under the tested conditions. The frequencies of the "resistant genotypes" are elevated in Ae. aegypti natural populations from Rio de Janeiro.

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. In addition, the toxicity and antioxidant capacities were tested in Artemia salina and rat erythrocytes, respectively. The results suggest that, an acute administration of the IF at doses of 25, 50, 75 and 150 mg/kg (intraperitoneal, i.p.) significantly (p < 0.05) reduced the marble burying behavior of the animals as compared to the vehicle group, which demonstrates a calming effect of this chemical. It was observed that, the pre-treatment with flumazenil (2.5 mg/kg, i.p.), an antagonist of the gamma-amino butyrinc acid (GABA A ) receptor, significantly reversed the marble burying behavioral activity in the animals treated with the IF 150 mg/kg dose. Moreover, the reduction in nitrite content and lipid peroxidation levels, while an increased in the reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16 mM) did not show toxicity in A. salina but exhibited a prominent antioxidant capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In conclusion, IF exhibited an anxiety-like effect in mice along with a potent antioxidant capacity, and we suppose it may have neuroprotective effects possibly via GABAergic transmission pathway., (Copyright © 2018. Published by Elsevier B.V.)

This work studied the cell transport of peptidase-generated peptides from cowpea bean proteins and their effects on mRNA expression of cholesterol-related genes in intestinal and liver cells. The ≤3 kDa hydrolysate was obtained and incubated with Caco-2 intestinal cells using Transwell® plates. HepG2 liver cells were incubated with synthetic analogues of peptides (MELNAVSVVHS and MELNAVSVVSH) identified by "de novo" peptide sequencing in the Caco-2 monolayer permeates. The mRNA expression of NPC1L1, ABCA1 and ABCG1 was measured in Caco-2 cells, in the presence or absence of ≤3 kDa hydrolysate and the expression of HMGCR, SREBP2, LXRα, AMPK1, was determined in the HepG2 cells in the presence or absence of synthetic peptides. Exposure of Caco-2 cells to cowpea ≤3 kDa hydrolysate (2.5 and 5 mg/mL) increased ABCG1 expression at 6 h and 12 h. SREBP2, HMGCR and LDLR mRNA levels were reduced in HepG2 cells after 24 h of treatment with MELNAVSVVHS peptide (50 μM and 100 μM). These results suggest that MELNAVSVVHS peptide is able to cross intestinal barrier and to modulate genes involved in cholesterol homeostasis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines was assessed against Schistosoma mansoni, a helminth that is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and 32.5μg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic activity than 1, and scanning electron microscopy analysis showed several morphological alterations in the tegument of worms in a concentration-dependent manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and normal cell lines. These results indicated that oxazines exerted direct effects on bacteria and parasite schistosomes. More importantly, since schistosomiasis control programs rely on one drug, praziquantel, oxazines may have the potential to become new antischistosomal agents., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bone biomaterials in support of sinus augmentation. Also, recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support clinically relevant bone formation when used to augment the maxillary sinus., Objectives: To evaluate local bone formation/dental implant osseointegration following implantation of two particulate bone biomaterials using the mini-pig sinus augmentation model., Methods: Nine adult Göttingen mini-pigs were used for evaluation of a biphasic ceramic (15%/85% HA/ß-TCP) and an allogeneic mineralized bone biomaterial. Treatments randomized to contralateral sinus sites included sham-surgery (control) and biomaterials. Two threaded dental implants (ø4.0 × 11.5 mm) were placed at each sinus site. The animals were euthanized at 8 weeks for histologic analysis., Results: Execution of the surgical protocol and healing was unremarkable. Limited infraorbital swelling was observed until suture removal. The biphasic ceramic and allogeneic bone biomaterials produced significantly increased bone formation (5.2 ± 1.9 mm and 4.9 ± 1.6 mm vs. 2.6 ± 0.5 mm, p < 0.05) and osseointegration (18.0 ± 6.0% and 25.1 ± 18.2% vs. 10.1 ± 8.0%, p < 0.05) over the sham-surgery control. No significant differences were observed between biomaterials., Conclusions: Implantation of biphasic ceramic or allogeneic bone biomaterials enhances bone formation in the mini-pig maxillary sinus, however, dental implant bone support is incomplete resulting in overall limited osseointegration., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E 2 , and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1β levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.

Aim: The objective of this report was to present histological characteristics and gene expression profile of newly formed bone following horizontal augmentation of the atrophic anterior maxilla using recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) versus an autogenous bone graft (ABG)., Methods: Bone core biopsies from 24 subjects participating in a randomized clinical trial were obtained at dental implant placement, 6 months following alveolar ridge augmentation using rhBMP-2/ACS (rhBMP-2 at 1.5 mg/ml; total dose 4.2 mg) or a particulate ABG harvested from the mandibular retro-molar region. A titanium mesh was used to provide wound stability and space for bone formation. Analysis included histological/histometric observations and gene expression profile of the newly formed bone., Results: rhBMP-2/ACS yielded bone marrow rich in capillaries, undifferentiated cells and bone lining cells compared with the ABG (p = 0.002). Whereas no significant differences were observed in total bone fraction (p = 0.53), non-vital bone particles trapped in lamellar vital bone were observed in the ABG group (p < 0.001). Real-time PCR showed greater BMP-2 and RUNX2 expression for rhBMP-2/ACS over the ABG (p = 0.001 and 0.0021, respectively), while the ABG exhibited greater expression of RANKL:OPG, BSP and OPN over rhBMP-2/ACS (p = 0.01, 0.005 and 0.0009, respectively)., Conclusions: Our observations suggest that formative biological processes explain bone formation following implantation of rhBMP-2/ACS, whereas remodelling, resorptive/formative processes, characterizes sites receiving ABGs., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The goal of this study was to increase knowledge about the antimicrobial activity of some synthetic Riparin-derived compounds, alone or in combination with fluoroquinolone antibiotics, against a strain of Staphylococcus aureus resistant to fluoroquinolone by way of overexpression of the NorA efflux pump., Methods and Results: Microdilution tests showed that Riparins A and B did not show any significant antibacterial activity against Staph. aureus strains. On the other hand, the intrinsic antibacterial activity increased with increasing lipophilicity of the compounds, in the following order: Riparin-D (MIC 256 μg ml -1 ; Log P 2·95) < Riparin-C (MIC 102 μg ml -1 ; Log P 3·22) < Riparin-E (MIC 16 μg ml -1 ; Log P 3·57). The addition of all riparins to growth media at subinhibitory concentrations caused an increase in the antibacterial activity of antibiotics against the NorA-overexpressing test strain. Riparin-B, which has two methoxyl groups at the phenethyl moiety, showed the best modulatory effect., Conclusions: Riparin-E is a good anti-staphylococci agent, while Riparin-B functions as a NorA efflux pump inhibitor., Significance and Impact of the Study: Our data suggest the possibility of using Riparin-B in combination with norfloxacin or ciprofloxacin for therapy of infections caused by multi-drug resistant Staph. aureus., (© 2016 The Society for Applied Microbiology.)

Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations., (Copyright © 2016 Elsevier B.V. All rights reserved.)