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Background: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies., Methods: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status., Results: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved., Conclusions: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Aim: Although most cases of coronavirus disease-2019 (COVID-19) are in humans, there is scientific evidence to suggest that the virus can also infect dogs and cats. This study investigated the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), canine coronavirus (CCV), and canine influenza virus (CIV) in domiciled and/or stray dogs from different locations in the State of Minas Gerais, Brazil, during the COVID-19 pandemic., Materials and Methods: In total, 86 dogs living in homes, on the streets, or in shelters in the cities of Taiobeiras, Salinas, Araçuaí, and Almenara were randomly selected for this study. The COVID Ag Detect ® Self-Test was used to detect SARS-CoV-2. The ACCUVET CCV AG TEST - CANINE CORONAVIROSIS ® was used to detect CCV, whereas canine influenza was detected using the ACCUVET CIV AG TEST - INFLUENZA CANINA ® . All collected data were mapped using QGIS 3.28.1 for spatial data analysis and the identification of disease distribution patterns. Descriptive analysis of the collected data, prevalence calculations, odds ratios (ORs), and 95% confidence intervals, when possible, was performed., Results: Of the 86 animals tested, only one dog tested positive for SARS-CoV-2 using the rapid test for viral antigen detection. No animals tested positive for CIV. Canine coronavirus was detected in almost half of the animals tested in Almenara. Severe acute respiratory syndrome-CoV-2 had a low prevalence (1.16%), versus 15.62% for CCV. Although the results were not significant, the age and breed of animals appeared to be associated with the occurrence of CCV. The results indicated that younger animals were 2.375-fold more likely to be infected. Likewise, purebred animals were more likely to contract the disease (OR = 1.944)., Conclusion: The results indicate the need to maintain preventive measures against CCV, canine influenza, and SARS-CoV-2 in dogs. More studies are needed to better elucidate the panorama of these diseases in dogs, mainly in underdeveloped and developing countries., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Santos, et al.)

Cocrystals are recognized as one of the most efficient approaches to improve aqueous solubility of Biopharmaceutical Classification System, BCS, classes II and IV drugs. Cocrystal discovery and the establishment of experimental conditions suitable for scale-up purposes are some of the main challenges in cocrystal investigation. In this work, the investigation of mechanochemical synthesis of norfloxacin cocrystals with picolinic and isonicotinic acids is performed, leading to the discovery of two new cocrystals of this important BCS class IV antibiotic, which were characterized through thermal, spectral and diffractometric analysis. Norfloxacin apparent aqueous solubility using the cocrystals is also presented, with higher values being obtained for all the investigated systems when compared to the pure drug. Norfloxacin has 3 polymorphs and several solvents/hydrates, which represents a challenge for obtaining pure cocrystal forms from solvent crystallization. This challenge was successfully overcome in this work, as experimental conditions to obtain the pure cocrystals (the new ones and also norfloxacin-nicotinic acid and norfloxacin-saccharin) were established using Crystal16 equipment. This is a crucial step to envisage future scale-up procedures and therefore a valuable information for the pharmaceutical industry., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interestss or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Parkinson's-disease (PD) is an incurable, age-related neurodegenerative disease, and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient's quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD; however, its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine are the metabolites that significantly discriminate parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, the biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, the glucose-alanine cycle, glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation.

Background: The economic burden of rare diseases on health systems is still not widely measured, with the generation of accurate information about the costs with medical care for subjects with rare diseases being crucial when defining health policies. Duchenne Muscular Dystrophy (DMD) is the most common form of muscular dystrophy, with new technologies recently being studied for its management. Information about the costs related to the disease in Latin America is scarce, and the objective of this study is to evaluate the annual hospital, home care and transportation costs per patient with DMD treatment in Brazil., Results: Data from 27 patients were included, the median annual cost per patient was R$ 17,121 (IQR R$ 6,786; 25,621). Home care expenditures accounted for 92% of the total costs, followed by hospital costs (6%) and transportation costs (2%). Medications and loss of family, and patient's productivity are among the most representative consumption items. When disease worsening due to loss of the ability to walk was incorporated to the analysis, it was shown that wheelchair users account for an incremental cost of 23% compared with non-wheelchair users., Conclusions: This is an original study in Latin America to measure DMD costs using the micro-costing technique. Generating accurate information about costs is crucial to provide health managers with information that could help establish more sustainable policies when deciding upon rare diseases in emerging countries., (© 2023. The Author(s).)

Several vaccines against COVID-19 are now available, based on different techniques and made by different laboratories spread around the world. With the roll out of the vaccination process in an advanced stage in many countries, the reduced risk of hospitalization due to the Omicron variant relative to the Delta variant infection, despite the higher transmission risk of Omicron, may lead to a misinterpretation of the results, as infection by Omicron is associated with a significant reduction in severe outcomes and shorter hospitalization time than the Delta variant. We compared the in-hospital mortality due to the Omicron (Jan-Mar 2022) with Gamma (Jan 2021) and Delta (Oct-Dec 2021) variants of patients in the Brazilian public health system. This study also discusses the decrease in booster vaccine effectiveness in patients hospitalized due to the Omicron variant compared with the Delta variant. Without a remodeling of vaccines for new variants, booster doses may be necessary with a shorter time interval.

Physical inactivity, associated with the ingestion of hypercaloric foods, contributes to obesity development. In contrast, physical exercise training (ET) can slow obesity progression. Vitamin (Vit) D, a hormone that regulates adipocyte metabolism, may represent a strategy to reduce obesity; however, it is currently not known whether Vit D enhances the anti-obesity benefits of physical exercise. We hypothesized that swimming ET may prevent Western diet (WD)-induced obesity, and that Vit D supplementation could enhance the anti-obesity actions of ET. Male Wistar rats were fed, from 21 to 90 days of age, on a standard diet, or a WD, in association or not (sedentary control [CTL-SED] and WD [WD-SED] groups) with swimming ET for 15 min/day, 3 days a week (exercised CTL [CTL-EXE] and WD [WD-EXE] groups). Additionally, at 60 days of age, half of the CTL-EXE and WD-EXE groups were submitted, or not, to oral Vit D supplementation (CTL-EXE-VD and WD-EXE-VD groups, respectively). At 91 days old, WD-SED rats displayed increased body weight, abdominal adiposity, hypercholesterolemia, hyperleptinaemia and high circulating levels of tumour necrosis factor (TNF)-α. Swimming ET attenuated the increase in abdominal adiposity induced by WD. Furthermore, the WD-EXE group exhibited reductions in glycaemia, triglyceridaemia, cholesterolaemia, leptinaemia and in plasma TNF-α concentrations. Vitamin D supplementation, combined with ET, did not provide any additive benefit against adiposity, only potentiating the effects of ET action on the reduction in triglyceridaemia. Exercise training, independently of Vit D, provides a strategy to attenuate the adiposity expansion that is induced by WD, mediated in part by reductions in leptinaemia and TNF-α levels., (© 2022 John Wiley & Sons Australia, Ltd.)

Aim: Pulmonary disease burden and biomarkers are possible predictors of outcomes in patients with COVID-19 and provide complementary information. In this study, the prognostic value of adding quantitative chest computed tomography (CT) to a multiple biomarker approach was evaluated among 148 hospitalized patients with confirmed COVID-19. Materials & methods: Patients admitted between March and July 2020 who were submitted to chest CT and biomarker measurement (troponin I, D-dimer and C-reactive protein) were retrospectively analyzed. Biomarker and tomographic data were compared and associated with death and intensive care unit admission. Results: The number of elevated biomarkers was significantly associated with greater opacification percentages, lower lung volumes and higher death and intensive care unit admission rates. Total lung volume <3.0 l provided further stratification for mortality when combined with biomarker evaluation. Conclusion: Adding automated CT data to a multiple biomarker approach may provide a simple strategy for enhancing risk stratification of patients with COVID-19.

Background: Regular exercise is an effective method for reducing pain and disability in patients with knee osteoarthritis (OA), as well as improving body composition. Thus, a combination of both resistance and aerobic training (circuit training) has shown to be promising for this population. However, access to physical therapy is limited by physical distance, social isolation, and/or treatment costs. Remote rehabilitation seems to be an effective way to minimize these barriers, but the benefits are dependent on the participants' adherence to the interventions provided at a distance. The objectives of this protocol are to compare the effects of a periodized circuit training applied via telerehabilitation with the same protocol applied in the face-to-face model for individuals with knee OA., Methods: This study presents a single-blinded protocol for a non-inferiority randomized controlled trial. One hundred participants diagnosed with knee OA (grades II and III Kellgren and Lawrence system), aged 40 years or more, and BMI < 30 kg/m 2 will be randomly divided into two groups: telerehabilitation (TR) and face-to-face (FtF) circuit training. The FtF group will perform a 14-week periodized circuit training protocol supervised by a physical therapist, 3 times a week. The TR group will perform the same exercise protocol at home, at least 3 times a week. In addition, the TR group will be able to follow the execution and orientations of the exercises by DVD, a website, and online file sharing tools, and they will receive periodic phone calls in order to motivate, clarify, and inform some aspects of knee OA. The primary outcomes are changes in self-reported pain intensity (visual analog scale (VAS)) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)), with a primary end-point of 14 weeks and a secondary end-point of 26 weeks. Secondary outcomes include changes in other clinical outcomes, in morphological characteristics, adherence, acceptability, and treatment perspective., Discussion: A circuit training through telerehabilitation may contribute to developing early intervention in the causative and potentiating factors of the knee OA, verifying the effects of a low-cost, non-pharmacological and non-invasive treatment., Trial Registration: Brazilian Registry of Clinical Trials (ReBEC) ID: RBR-662hn2. Registered on 31 March 2019. Link: http://www.ensaiosclinicos.gov.br ; Universal Trial Number (UTN) of World Health Organization: U1111-1230-9517., (© 2021. The Author(s).)

The purpose of this systematic review was to analyze the influence of occlusal reduction on the postoperative pain levels after endodontic treatment (instrumentation and obturation of the root canal system). This review followed the PRISMA statement and was registered at PROSPERO (CRD42018107918). Two independent reviewers searched the Lilacs, Cochrane Library, PubMed (Medline), Web of Science, Scopus, Scielo, and ScienceDirect for articles published until April 2021. The research question was, "Does occlusal reduction decrease postoperative pain in endodontically treated teeth?". Only randomized clinical trials were included. The RevMan 5 program was used for meta-analysis, calculating the relative risk (RR) and 95% confidence interval (CI) of the dichotomous outcome (presence or absence of pain). The search strategies retrieved 4114 studies. Twelve studies were included for qualitative analysis and nine for quantitative analysis. The meta-analysis results did not reveal a significant difference in the reduction of postoperative pain levels for endodontic instrumentation at 6, 12, 24, 48 h and for endodontic obturation at 6 or 12 h after occlusal reduction. According to the GRADE tool, the analyzed outcome was classified as having a moderate level of certainty. It is concluded that occlusal reduction does not interfere with postoperative pain levels after endodontic treatment.

Objectives: To analyze if socioeconomic characteristics as lower education and lower family income are associated factors with the combination of pain catastrophizing and kinesiophobia in patients with knee osteoarthritis (KOA)., Methods: This cross-sectional study included 140 participants aged 40 years or older with KOA grades II and III. Based on the Pain Catastrophizing Scale (PCS) and the Tampa Scale of Kinesiophobia (TSK), four groups were identified: non-catastrophic/non-kinesiophobic (NC/NK), non-catastrophic/non-kinesiophobic (NC/K), catastrophic/non-kinesiophobic (C/NK), and catastrophic/kinesiophobic (C/K). Pain intensity was measured using the visual analog scale (VAS). The 30-s chair stand test was performed to access physical function. Sociodemographic characteristics included age, sex, years of formal education (0 to 11 and > 11), and family income (up to 2 minimum wages and > 2). Multinomial regression analysis adjusted for age, radiographic severity, physical function, and pain intensity was used to determine the association between lower education and lower family income with the combination of pain catastrophizing and kinesiophobia., Results: Only lower education was independently associated with the combination of pain catastrophizing and kinesiophobia (OR = 3.96 CI 95% 1.01-15.51)., Conclusions: Lower education but not lower family income was an important associated factor with the combination of pain catastrophizing and kinesiophobia in individuals with knee osteoarthritis. Thus, physician and physical therapist must pay attention on this important socioeconomic characteristic while conducting the treatment, since specific strategies of approach could be necessary for those patients. Key points • Lower education is an important associated factor with the combination of pain catastrophizing and kinesiophobia in individuals with knee osteoarthritis. • Physician and physical therapist must pay attention on patients schooling while conducting the treatment.

Background and Aim: Broiler meat is susceptible to lipid oxidation due to its high content of unsaturated fatty acids, especially when stored for a long time. Concerning with that problem, we can add natural compounds to the animal feed, as the plant essential oils, which have antioxidant, antimicrobial, and antifungal activities. The objective of this study was to evaluate the antioxidant activity, fatty acid profile, and chemical composition of the meat of broilers fed with diets containing different essential oil, including lemongrass ( Cymbopogon flexuosus ) and pedestrian tea ( Lippia aff. rotundifolia )., Materials and Methods: The experimental design used was a 4×4 factorial scheme (storage time×diets), and each treatment was repeated thrice. The treatments were applied as negative control (without antimicrobial); positive control (ration supplemented with 10 ppm of enramycin and 42 ppm of salinomycin), lemongrass (ration with 120 mg of essential oil of lemongrass for each kilogram of live weight of the animals), and pedestrian tea (ration with 120 mg of essential oil of pedestrian tea for each kilogram of live weight of the animals). Storage was performed after slaughter and evaluated monthly for 4 months., Results: The inclusion of lemongrass oil and pedestrian tea in the broiler diet did not change the ether extract content of the meat sample obtained from thigh and drumstick. The storage time promotes an increase in the moisture loss of the meat from the 2 nd month in all treatments. There was an interaction between the additive and storage time for moisture loss. In the 2 nd month of storage, the meat from broilers fed the antibiotic-containing feed had a lower moisture loss than those from broilers in the other treatment groups. The fatty acid profile did not differ statistically between the different treatment groups. The inclusion of additives in the food dropped the lipid oxidation at the 2 nd month of storage. From the 3 rd month, however, only the essential oils showed antioxidant effect., Conclusion: Antioxidant activity was positive for treatments that included essential oils. The lemongrass oil and pedestrian tea can be used as antioxidant additives in broiler diets to improve the oxidative stability of thigh-drumstick meat during storage. The results of the study suggest a good prospective for further research with profitability of usage essentials oils examined, for their economical application as feed components in broiler nutrition., (Copyright: © Azevedo, et al.)

AbstractThe lifestyle of symbiotic species in the genus Synalpheus can vary from pair living to eusocial. A pair-living social system commonly implies the adoption of a monogamous mating system. In this study, we used the symbiotic shrimp Synalpheus brevicarpus in association with the sponge Dysidea sp. to test the hypothesis that heterosexual pairs of symbiotic shrimps can adopt a monogamous mating system when living in association with a morphologically complex host. We collected a total of 40 sponges, which were inhabited by 76 shrimps: 41 males, 33 females, and 2 juveniles. Synalpheus brevicarpus is sexually dimorphic, with males displaying proportionately larger weaponry (snapping claws) and a smaller average body size than females. Sponges were more often inhabited by a pair of heterosexual shrimps than expected by chance. Larger sponges were inhabited by more than one pair of shrimps in which the sex ratio did not differ significantly from 1∶1. Pairs of heterosexual shrimps were recorded, with females carrying embryos in all stages of embryonic development. Our results indicate that S. brevicarpus is a pair-living shrimp with a monogamous social and mating system that may also guard spaces or areas within its sponge host. Our hypothesis of monogamy is supported by the observations on pair living, sex ratio, and sexual dimorphism in body size and weaponry in this species.

Magnesium (Mg[Formula: see text] is an essential mineral for several cellular functions. The concentration of this ion below the physiological concentration induces recurrent neuronal discharges both in slices of the hippocampus and in neuronal cultures. These epileptiform discharges are initially sensitive to the application of [Formula: see text]-methyl-D-aspartate (NMDA) receptor antagonists, but these antagonists may lose their effectiveness with prolonged exposure to low [Mg[Formula: see text]], when extracellular Ca[Formula: see text] reduction occurs, typical of ictal periods, indicating the absence of synaptic connections. The study herein presented aimed at investigating the effect of reducing the [Mg[Formula: see text]] during the induction of Nonsynaptic Epileptiform Activities (NSEA). As an experimental protocol, NSEA were induced in rat hippocampal dentate gyrus (DG), using a bath solution containing high-K[Formula: see text] and zero-added-Ca[Formula: see text]. Additionally, computer simulations were performed using a mathematical model that represents electrochemical characteristics of the tissue of the DG granular layer. The experimental results show that the reduction of [Mg[Formula: see text]] causes an increase in the duration of the ictal period and a reduction in the interictal period, intensifying epileptiform discharges. The computer simulations suggest that the reduction of the Mg[Formula: see text] level intensifies the epileptiform discharges by a joint effect of reducing the surface charge screening and reducing the activity of the Na/K pump.

Introduction/objective: To evaluate the effects of a periodized circuit training (CT) compared with a conventional strength training (ST) and an educational protocol (EP) on body composition, metabolic parameters, muscle strength, pain, and physical performance in patients with knee osteoarthritis (KOA)., Method: This study followed a randomized controlled trial design. A sample of sixty-one patients with KOA, 40-65 years old and BMI < 30 kg/m 2 , were randomly divided into three 14-week protocols: CT, ST, or EP. The CT performed whole body exercises organized in circuit, 3 times a week. The ST performed conventional resistance exercises also 3 times a week, and the EP joined in educational meetings twice a month. Body composition (dual-energy X-ray absorptiometry (DXA)); metabolic parameters (abdominal obesity, triglyceride, HDL, blood pressure and fasting glucose), knee maximal isometric voluntary contraction (MIVC) extension and flexion, performance-based tests (40-m walk test, 30-s chair test, and stair climb test), self-reported pain, stiffness, and physical function (WOMAC) and pain catastrophism were evaluated at baseline and follow-up. Repeated measures ANOVA were used to compare differences between groups (CTxSTxEP) at the different times of assessment (baseline × follow-up). When group-time interaction was found, a one-way ANOVA, followed by a Bonferroni post hoc test, was used to compare groups in each time point; while a paired t test was used to verify the time effect in each group. Additionally, the training effect was analyzed in terms of the percent change (Δ%). Effect size was calculated for post intervention (week 14) between groups. For all analyses a significance level of 5% was adopted (p < 0.05)., Results: The CT was the only protocol that presented significant lower body mass (p = 0.018; Δ% = - 1.4), fat mass (p = 0.017; Δ% = - 10.3), %fat mass (p < 0.001; Δ% = - 13.9), adipose indices (%fat trunk/%fat legs p = 0.031; Δ% = 7.8; fat mass/height 2 p = 0.011; Δ% = - 15.1; trunk/limb fat mass p = 0.012; Δ% = - 8.2; visceral adipose tissue (VAT) volume (cm 3 ) p = 0.039; Δ% = - 11.6; VAT area (cm 2 ) p = 0.044; Δ% = - 12.2), blood pressure levels (SBP p = 0.042; Δ% = - 3.4 and DBP p = 0.001; Δ% = - 4.9), higher lean mass and HDL (p < 0.001; Δ% = 5.9) compared to baseline. CT and ST presented lower WOMAC pain, stiffness and physical function (p < 0.001; Δ% = - 64.0 for CT and p < 0.001; Δ% = 0.001; Δ% = - 46.4 for ST in WOMAC total score, pain catastrophizing (p < 0.001; Δ% = - 66.7 for CT and p < 0.001; Δ% = - 61.5 for ST) a higher functional performance (30 s chair test: p < 0.001; Δ% = 45.7 for CT and p < 0.001; Δ% = 26.9 for ST; 40 m walk test: p < 0.001; Δ% = 26.7 for CT and p < 0.001; Δ% = 12.5 for ST; stair climb test: p = 0.002; Δ% = - 33.9 for CT and p < 0.001; Δ% = - 18.8 for ST) and knee extension MIVC (p < 0.001; Δ% = 21.92 for CT and p < 0.001; Δ% = 30.25 for ST)., Conclusion: A periodized CT model reduces visceral adipose tissue, SBP and DBP, and improves HDL, important cardiovascular and metabolic risk factors, in patients with KOA. Both trained groups (CT and ST) improve self-reported clinical symptoms, muscle strength, and physical performance in this sample., Trial Registration Number: ClinicalTrials.gov , NCT02761590 (registered on May 4, 2016)., Key Points: • A 14-week periodized circuit training reduces visceral adipose tissue, systolic and diastolic blood pressure, and improves HDL blood levels in patients with knee osteoarthritis. • Both periodized circuit training and conventional strength training improve clinical symptoms, functional performance and muscle strength in this sample.

Objective: To analyze the influence of a 14-week periodized circuit training (CT) protocol on thigh intermuscular fat and muscle quality (force per unit area of lean tissue) in patients with knee osteoarthritis (KOA)., Design: Randomized controlled trial METHODS: Sixty-one selected participants with KOA grades 2 and 3, 40-65 years old, and BMI < 30 kg/m 2 were randomized into three groups: CT, conventional strength training (ST), and educational protocol (EP). The CT and ST protocols consisted of 14-week training protocols conducted 3 times a week. The CT group performed exercises stratified as light, moderate, and intense, arranged progressively in a circuit model. The ST group performed conventional strength exercises, and the EP group participated in lectures twice a month about healthy lifestyles. Baseline and follow-up (week 0 and week 14) evaluations were conducted for thigh intermuscular fat (computed tomography), knee extension maximal isometric voluntary contraction (MIVC), and muscle quality (knee extension MIVC/muscle mass cross-sectional area)., Results: Only the CT group presented significant reductions in thigh intermuscular fat (p = 0.003) and significantly lower values in week 14 compared with the EP (p = 0.032). Both trained groups presented significant increases in muscle mass area (p=0.002 for CT and p=0.008 for ST) and increments in knee extension MIVC (p=0,033 for CT nd p=0.019 for ST) in week 14 compared with the EP and increases in muscle quality (p = 0.004 and 0.042)., Conclusion: It can be concluded that a 14-week periodized CT protocol attenuates thigh intermuscular fat and improves muscle quality in patients with KOA., Trial Registration: ClinicalTrials.gov, NCT02761590; https://clinicaltrials.gov/ct2/show/NCT02761590Key Points•Fourteen weeks of periodized circuit training attenuates thigh intermuscular fat in patients with knee osteoarthritis.•Circuit training is as effective as strength training for improving muscle mass, strength, and quality.

Background: The use of ultrasound for localized fat treatment on possible psychological influences is little explored to date. Therefore, it is relevant to elaborate studies that include a placebo group in order to measure the real effects of the exclusive application of ultrasound., Objectives: To verify the influence of ultrasound application for localized fat treatment on clinical, functional, and psychological outcomes., Methods: Thirty female participants who were candidates for localized abdominal fat treatment were included and randomly divided into three groups: control (CG, n = 10), experimental (EG, n = 10), and placebo (PG, n = 10). The CG did not receive any intervention. The EG received 10 ultrasound sessions for 20 minutes. For the PG, ultrasound was also applied for 20 minutes, but with zero intensities. Anthropometric assessment, cardiovascular parameters, circumference measurements, photography, endurance test, and subjective questionnaires were performed before and after the treatment protocols., Results: The EG photographs show an improvement of 60% in the visual appearance. Regarding the other analyzed outcomes, no statistically significant differences were found between moments and groups ( P > 0.05)., Conclusions: Pretreatment and posttreatment photographs analysis demonstrate visual improvement in the appearance of abdominal localized fat in the EG. However, ultrasound application, when compared with CG and PG, is not a superior method for improving clinical, functional, and psychological parameters., (© 2020 The Aesthetic Society.)

Aim: To evaluate the cyclic fatigue resistance of Reciproc blue (RB) 40/0.06 instruments tested at room temperature (20° ± 0.5°C) and at body temperature (37° ± 0.5°C) in a simulated stainless steel canal., Materials and Methods: Twenty-four new RB 40/0.06 instruments were randomly divided into two groups ( n = 12) according to the temperature used. Dynamic fatigue testing was performed using an artificial stainless steel canal with a 60° curvature angle and a 5-mm radius of curvature. The temperature was controlled throughout the experiment with an underwater thermometer and a thermostat. The data were analyzed descriptively using the IBM SPSS 23.0 program, considering p < 0.05., Results: The time to fracture of the RB instruments differed significantly between the two temperatures (1083.82 seconds at 20°C and 403.80 seconds at 37°C). No significant differences were found in fragment size., Conclusion: An increase in temperature reduces the cyclic fatigue resistance of RB 40/0.06 instruments. The results of the study suggest that an intracanal cooling system can be favorable to the fracture resistance of the tested instruments., Clinical Significance: A cooling system of the root canal system is important in endodontic as it favors the cyclic fatigue resistance of Ni-Ti instruments.

Human ingestion of antimicrobial residues in dairy products is a problem of public health. In this study we evaluated antibacterial effectiveness of aqueous and ethanolic leaf extracts of Mangifera indica L. as a natural alternative for reduction of Staphylococcus spp. biofilms. Eight Staphylococcus spp. strains from cows with mastitis and the Staphylococcus aureus strain (ATCC 25923) were evaluated. High performance liquid chromatography indicated the presence of phenolic compounds in the aqueous extract. Agilent Technologies gas chromatography revealed the presence of phenolic compounds, carbohydrates, and gallic acid in ethanolic extract. The tannin contents were 2.27 ± 0.01 and 2.67 ± 0.01% for ethanolic extract and aqueous extract, respectively. Extracts were evaluated in agar diffusion test and the size of inhibition zones were compared. The ethanolic extract was the most effective, showing minimum inhibitory concentrations and minimum bactericidal concentrations between 1.8-7.5 and 15.1-45.3 mg/ml, respectively. After tannin removal, the extracts were less effective, indicating these secondary metabolites as one of the main antibacterial compounds. The ethanolic extract at 45.3 mg/ml reduced mature biofilms in teat rubber (average: 3.91 log reduction) and stainless steel (average: 3.87 log reduction) after 5 min of contact. The extracts of M. indica leaves represent natural alternatives against Staphylococcus spp. strains and the ethanolic extract shows potential as a natural sanitizer.

Background and Aim: The term ESKAPE, recognized by the WHO, is an acronym, which refers to the pathogens Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter spp., which is extremely virulent and multidrug-resistant. Although the term is used to designate nosocomial pathogens, in a milking environment, strains of Methicillin-resistant S. aureus have been isolated from cattle diagnosed with clinical and subclinical mastitis. Resistant strains may be involved in the transfer of genes conferring resistance to beta-lactam antimicrobials among the species of microorganisms related to mastitis etiology. This study aimed to trace the phenotypic and genotypic profiles of susceptibility to beta-lactams in S. aureus isolated from milk of cattle diagnosed with subclinical mastitis obtained from different rural properties located in the North of Minas Gerais State, Brazil., Materials and Methods: Sixteen microorganisms previously identified as S. aureus isolated from milk of cattle diagnosed with subclinical mastitis were submitted to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF), mass spectrometry, and polymerase chain reaction (PCR) analysis for microbial species confirmation. The S. aureus beta-lactams antimicrobial phenotypic resistance profile was investigated by disk diffusion method. PCR methods were also performed to investigate the S. aureus genotypic beta-lactams resistance profile. For this purpose, bla Z , mec A, mec ALGA251 , bla Oxa23 , and bla KPC genes were screened among S. aureus isolates. The genetic diversity of S. aureus by fingerprint random amplified polymorphic DNA (RAPD)-PCR was also performed in this study., Results: All isolates showed phenotypic resistance to at least three beta-lactams, among which was meropenem. None of the isolates tested positive for the genes mec ALGA251 , bla Oxa23 , and bla KPC ; however, the presence of the genes bla Z and mec A was detected among the isolates. The fingerprint analysis divided isolates into two distinct groups and 15 different subgroups. Despite the presence of clonality among the isolates, the PCR-RAPD analysis unveiled a heterogeneous profile with genetic diversity among the S. aureus isolates., Conclusion: In this study, we identified beta-lactams resistant S. aureus strains isolated from the milk of cows diagnosed with subclinical mastitis. The S. aureus beta-lactams resistance was investigated using a phenotypic and genotypic approach. We believe that molecular epidemiology, improved knowledge, and genetic basis of resistance to beta-lactams might assist in asserting guidelines for better management practices of dealing with subclinical mastitis and mapping of origin of resistant pathogens in the studied Brazilian area., (Copyright: © Souza, et al.)

Objectives: To investigate any differences in muscle architecture (fascicle angle, fascicle length, and muscle thickness) and muscle strength in people of different ages with and without knee osteoarthritis (OA)., Methods: This is a cross-sectional study conducted with 40 individuals with and 40 without knee OA. Four groups were analyzed, middle-aged OA group (KL II/III) aged 40-50 years (n = 20), middle-aged healthy (H) group aged 40-50 years (n = 20), older OA group (KL II/III) aged 70 years and over (n = 20), and older H group, aged 70 years and over (n = 20). Outcomes analyzed were isometric and isokinetic peak torque of knee extensors, level of physical activity, self-reported pain level, and vastus lateralis fascicle length, fascicle angle, and muscle thickness assessed by ultrasound. One-way ANOVA was used to identify differences between groups, followed by the Tukey post hoc test., Results: There were no differences between the middle-aged OA group and older H group for any variables. The older OA group presented the smallest muscle architecture parameters and worst isometric and concentric peak torques compared to the other three groups (p < 0.001). In contrast, the middle-aged H group presented the largest muscle architecture parameters and was the strongest group compared to the others (p < 0.001)., Conclusions: The presence of knee OA is associated with early muscular changes and seems to intensify these thigh changes that are similar to the effects of the aging process.

Micheletti, JK, Vanderlei, FM, Machado, AF, de Almeida, AC, Nakamura, FY, Netto Junior, J, and Pastre, CM. A new mathematical approach to explore the post-exercise recovery process and its applicability in a cold water immersion protocol. J Strength Cond Res 33(5): 1266-1275, 2019-The objective of this study was to propose a mathematical model to analyze the post-training recovery of perceptive, functional, metabolic, and autonomic parameters from the use of cold water immersion (CWI) through isolated and combined analysis. Following simulated training, 64 male soccer players were randomized into an experimental group (EG: CWI, 13 ± 1° C; 15 minutes) and a control group (CG: passive recovery; 15 minutes). Perceptive (soreness and perception of recovery), autonomic (heart rate variability [HRV]), metabolic (lactate concentration), and functional parameters (squat jump, T agility test, sprint test, 40-second test, and maximal voluntary isometric contraction) were analyzed before and at specific moments after training (without exceeding 2 hours after training). The variables were analyzed using the raw data, dichotomization of each variable (isolated analysis), and through a mathematical model using the combination of all parameters analyzed (combined analysis). The combined analysis did not demonstrate better efficacy of the EG compared with the CG (69.17 and 63.4%, p = 0.09). In the isolated analysis, a chance of the technique being better was observed in the metabolic parameter at 1 and 2 hours after training (odds ratio, 95% confidence interval = 3.75 [1.01-13.88] and 11.11 [1.25-98.49]), respectively, and in the autonomic parameter at 40-45 minutes after training (4.4 [1.09-17.67]). For the raw data, all parameters analyzed presented recovery by 2 hours after training for both groups. Based on the proposed mathematical model, it is concluded that CWI is not better than the control condition. However, considering the analysis of variables in isolation, the technique presents a better chance of recovery for blood lactate concentration and HRV.

Knee osteoarthritis is a chronic degenerative joint disease, influenced by inflammatory, mechanical and metabolic processes. Current literature shows that thigh muscles of people with knee osteoarthritis can have increased infiltration of fat, both between and within the muscles (inter- and intramuscular fat). The fatty infiltration in the thigh in this population is correlated to systemic inflammation, poor physical function, and muscle impairment and leads to metabolic impairments and muscle disfunction. The objective of this study is to systematically review the literature comparing the amount of fatty infiltration between people with knee osteoarthritis and healthy controls. A literature search on the databases MEDLINE, Embase, CINAHL SPORTDiscuss, Web of Science and Scopus from insertion to December 2018, resulted in 1035 articles, from which 7 met inclusion/exclusion criteria and were included in the review. All included studies analyzed the difference in intermuscular fat and only one study analyzed intramuscular fat. A meta-analysis (random effects model) transforming data into standardized mean difference was performed for intermuscular fat (six studies). The meta-analysis showed a standardized mean difference of 0.39 (95% confidence interval from 0.25 to 0.53), showing that people with knee osteoarthritis have more intermuscular fat than healthy controls. The single study analyzing intramuscular fat shows that people with knee osteoarthritis have more intramuscular fat fraction than healthy controls. People with knee osteoarthritis have more fatty infiltration around the thigh than people with no knee osteoarthritis. That conclusion is stronger for intermuscular fat than intramuscular fat, based on the quality and number of studies analyzed.

Given the practicality and low cost of using elastic resistance in training for different populations and its effectiveness in a range of outcomes, a comparison with conventional devices could clarify and quantify the benefits provided by both mode. To compare the effects of resistance training with elastic devices (tubes and Thera-Bands) and conventional devices (weight machines and dumbbells) on the outcome muscular strength. A search was performed in the databases PubMed/MEDLINE, EMBASE, PEDro (Physiotherapy Evidence Database), and CENTRAL (Cochrane Central Register of Controlled Trials) from the earliest records up to 20 December 2017. Data were pooled into a meta-analysis and described as standardized mean difference with a 95% confidence interval (registration number: CRD42016042152). Eight studies were included. The results of the meta-analysis demonstrated no superiority between the methods analyzed for lower limb (SMD = -0.11, 95% CI -0.40, 0.19, p = 0.48) or upper limb muscular strength (SMD=0.09; 95% CI -0.18, 0.35; p = 0.52) [corrected]. Elastic resistance training is able to promote similar strength gains to conventional resistance training, in different population profiles and using diverse protocols., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The objective of this study is to analyze the influence of a 14-week periodized circuit training protocol on patients with knee osteoarthritis (OA), in randomized intervention groups, on thigh intermuscular adipose tissue (interMAT), body composition, systemic inflammation, cartilage degradation, and its repercussion on pain, functional performance and quality of life., Methods: This study presents a protocol for a randomized controlled trial. Sixty selected participants diagnosed with knee OA grades II and III, 40-65 years old and BMI < 30 kg/m 2, will be randomly divided into three groups:periodized circuit training, strength training, and educational protocol. The circuit training and strength training protocols consist of 14-week training protocols conducted 3 times a week. The circuit training group will perform selected exercises previously stratified as light, moderate, and intense, arranged progressively in a circuit model, the strength group will perform regular strength exercises, and the educational protocol group will participate in a 14-week protocol with lectures twice a month about healthy lifestyles. Baseline and follow-up evaluations will be conducted for thigh interMAT (computed tomography), body composition (DXA), inflammation (IL-1β, IL-6, IL-10, TNF-α, leptin, and adiponectin), and joint degradation biomarkers (uCTX-II and sCOMP), performance-based tests (30s Chair Stand Test, 40 m Fast-paced Walk Test and Stair Climb Test), quadriceps and hamstring maximal isometric voluntary contraction (MIVC), and questionnaires (WOMAC and pain catastrophizing scale). Repeated measures ANOVA will be used to compare differences between groups (circuit training X strength training X educational protocol) at the different times of assessment (baseline x follow-up or baseline x during protocol x follow-up) for each of the dependent variables. When significant main effects were found, the pots hoc Bonferroni test will be used to identify statistical differences. A significance level of 5% (p < 0.05) will be adopted., Discussion: This will be the first randomized controlled trial to assess the effects of a circuit training protocol on patients with knee OA on thigh intermuscular adipose tissue (interMAT). Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of a low-cost, non-pharmacological, and non-invasive treatment for knee OA patients has the potential for immediate and high clinical impact., Trial Registration: ClinicalTrials.gov, NCT02761590 , registered in May 4, 2016.

Wallinia brasiliensis n. sp. is described from the intestine of two species of tetras-Astyanax fasciatus (Cuvier, 1819) and Astyanax lacustris Lucena and Soares, 2016-collected from the Batalha River in São Paulo State, Brazil. The new species can be clearly distinguished from the other three congeneric species by its vitelline follicles extending from the genital pore to the end of the caeca, eggs lacking operculum, a larger egg size with a consequently lower number relative to the other three species, and the ovary located opposite the anterior testis. The validity of the new species was confirmed through a phylogenetic analysis of the 28S rRNA gene which showed that the new species is the sister taxon to Wallinia mexicana Pérez-Ponce de León, Razo-Mendivil, Mendoza-Garfía, Rubio-Godoy and Choudhury, 2015, a species infecting Astyanax mexicanus (De Filippi, 1853) in Mexico.

Competing Interests: There are no conflicts of interest.

A residual liquid inoculum (RLI) was used to decolourise solutions of Acid Yellow 25 (AY25) and Direct Violet 51 (DV51) azo dyes. The RLI was obtained through anaerobic digestion of food waste from a university restaurant. The concentration of bacteria in the RLI was 8.45 × 10 7 CFU mL -1 . Dye solutions (50 μg mL -1 ) were inoculated with the RLI (20% v/v) and incubated at room temperature. The decolourisation studies took place at microaerophilic and in-batch conditions and at pH = 2.50. Initially, the dyes were taken up from solution by biosorption; maximum colour removal was achieved after 3 hours of incubation, with 88.66% for AY25 and 77.65% of DV51. At prolonged incubation times (3-96 hours) decolourisation was mainly attributed to biodegradation of the azo solutions, with breakage of the azo bond, as detected by UV-VIS spectroscopy and Fourier transform infrared (FT-IR) analysis. Analysis of UV-VIS absorption rates of dyes showed, however, that AY25 was more readily biodegradable whereas DV51 was more recalcitrant to the action of the RLI.

Spirulina platensis (SPI) is a cyanobacterium, presenting anti-inflammatory and antioxidant actions. Considering the importance of inflammation and oxidative stress in Parkinson's disease (PD), SPI neuroprotective effects were evaluated in a model of PD. Male Wistar rats were divided into: sham-operated (SO), untreated 6-OHDA and 6-OHDA treated with SPI (25 and 50 mg/kg, p.o.). The 6-OHDA was injected into the right striata and SPI treatments started 24 h later for 2 weeks. The SO and untreated 6-OHDA-lesioned groups were administered with distilled water, for the same period. Afterwards, the animals were subjected to the apomorphine-induced rotational test and euthanized for striatal measurements of DA and DOPAC, nitrite and TBARS and immunohistochemistry assays for TH, DAT, iNOS and COX-2. SPI reduced the apomorphine-induced rotational behavior, DA and DOPAC depletions and nitrite and TBARS increases, at its high dose. Furthermore, TH and DAT immunoreactivities in the lesioned striatum of the untreated 6-OHDA-lesioned group were attenuated by SPI. Similarly, immunoreactivities for iNOS and COX-2 were also decreased after SPI treatments. In conclusion, we showed that behavioral and neurochemical alterations in hemiparkinsonian rats were partly reversed by SPI, characterizing the neuroprotective potential of Spirulina and stimulating translational studies focusing on its use as an alternative treatment for PD.

Background: Cold water immersion (CWI) is a commonly used recuperative strategy. However there is a lack of standardization of protocols considering the duration and temperature of application of the technique and the stress model. Therefore it is important to study the issue of dose response in a specific stress model. Thus the objective was to analyze and compare the effects of CWI during intense post-exercise recovery using different durations and temperatures of immersion., Methods: One hundred and five male individuals were divided into five groups: one control group (CG) and four recovery groups (G1: 5' at 9±1 °C; G2: 5' at 14±1 °C; G3: 15' at 9±1 °C; G4: 15' at 14±1 °C). The volunteers were submitted to an exhaustion protocol that consisted of a jump program and the Wingate Test. Immediately after the exhaustion protocol, the volunteers were directed to a tank with water and ice, where they were immersed for the recovery procedure, during which blood samples were collected for later lactate and creatine kinase (CK) analysis. Variables were collected prior to the exercise and 24, 48, 72, and 96 hours after its completion., Results: For the CK concentration, 15 minutes at 14 °C was the best intervention option, considering the values at 72 hours after exercise, while for the moment of peak lactate an advantage was observed for immersion for 5 minutes at 14 °C. Regarding the perception of recovery, CWI for 5 minutes at 14 °C performed better long-term, from the time of the intervention to 96 hours post-exercise. For pain, no form of immersion responded better than the CG at the immediately post-intervention moment., Conclusions: There were no differences in behavior between the CWI intervention groups for the outcomes studied.

Background: Toll-interacting protein is a negative regulator in the TLR signaling cascade, particularly by impeding the TLR2 and, TLR4 pathway. Recently, TOLLIP was shown to regulate human TLR signaling pathways. Two common TOLLIP polymorphisms (rs5743899 and rs3750920) were reported to be influencing IL-6, TNF and IL-10 expression. In this study, TOLLIP variants were investigated to their relation to Plasmodium vivax malaria in the Brazilian Amazon., Methods: This cohort study was performed in the municipalities of Careiro and, Manaus, in Western Brazilian Amazon. A total of 319 patients with P. vivax malaria and, 263 healthy controls with no previous history of malaria were included in the study. Genomic DNA was extracted from blood collected on filter paper, using the QIAamp ® DNA Mini Kit, according to the manufacturer's suggested protocol. The rs5743899 and rs3750920 polymorphisms of the TOLLIP gene were typed by PCR-RFLP., Results: Homozygous individuals for the rs3750920 T allele gene had twice the risk of developing malaria when compared to individuals homozygous for the C allele (OR 2.0 [95% CI 1.23-3.07]; p = 0.004). In the dominant model, carriers the C allele indicates protection to malaria, carriers of the C allele were compared to individuals with the T allele, and the difference is highly significant (OR 0.52 [95% CI 0.37-0.76]; p = 0.0006). The linkage disequilibrium between the two polymorphisms was weak (r 2  = 0.037; D' = 0.27)., Conclusions: These findings suggest that genes involved in the TLRs-pathway may be involved in malaria susceptibility. The association of the TOLLIP rs3750920 T allele with susceptibility to malaria further provides evidence that genetic variations in immune response genes may predispose individuals to malaria.

The hydroethanolic root extract of Arrabidaea brachypoda, from Bignoniaceae family, a Brazilian medicinal plant, demonstrated significant in vivo gastroprotective effects using different in vivo assays. The activity was evaluated in several models of experimental gastric ulcer in rats (absolute ethanol, glutathione depletion, nitric oxide depletion, non-steroidal anti-inflammatory drugs, pylorus ligation and acetic acid). Using 300 mg/kg (p.o.) the extract significantly reduced gastric injury in all models. In depth phytochemical investigation of this extract led to the isolation of two previously undescribed phenylethanoid glycosides derivatives and seven unusual glycosylated dimeric flavonoids. The structures were elucidated using UV, NMR and HRMS analysis. Absolute configuration of the dimeric flavonoids was performed by electronic circular dichroism (ECD) spectroscopy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Inflammatory bowel disease (IBD) is a chronic and disrupted inflammation of the gastrointestinal tract. IBD have two main conditions, Crohn's disease and ulcerative colitis, and have been extensively investigated in recent years. Antibiotics derived from salicylates, steroids, immunosuppressors, and anti-TNF therapy are part of the therapeutic arsenal for IBD. However, very often patients stop responding to treatments over the time. In this context, searching for alternative agents is crucial for IBD clinical management. Natural products derived from medicinal plants are an interesting therapeutic alternative, since several studies have proven effective treatments in animal models of intestinal inflammation. Several naturally occurring compounds are potent antioxidants, both as free radical scavengers and as modulators of antioxidant enzymes expression and activity. A number of natural compounds have also been proved to inhibit the release of proinflammatory cytokines, decreasing the activation of nuclear factor κ B (NF- κ B), which is important to the inflammatory response in IBD. The alkaloids are substances of a very diverse class of plant secondary metabolites; an extensive list of biological activities has been attributed to alkaloids, such as being anticholinergic, antitumor, diuretic, antiviral, antihypertensive, antiulcer, analgesic, and anti-inflammatory. In the present work, studies on the pharmacological activity of alkaloids in experimental models of IBD were reviewed., Competing Interests: The authors declare that they have no competing interests.

The use of antibodies in immunodiagnostic kits generally implies the conjugation of these proteins with other molecules such as chromophores or fluorochromes. The development of more sensitive quality control procedures than spectrophotometry is essential to assure the use of better fluorescent conjugates since the fluorescent conjugates are critical reagents for a variety of immunodiagnostic kits. In this article, we demonstrate a new flow cytometric protocol to evaluate conjugates by molecules of equivalent soluble fluorochromes (MESF) and by traditional flow cytometric analysis. We have coupled microspheres with anti-IgG-PE and anti-HBSAg-PE conjugates from distinct manufactures and/or different lots and evaluated by flow cytometry. Their fluorescence intensities were followed for a period of 18 months. Our results showed that there was a great difference in the fluorescence intensities between the conjugates studied. The differences were observed between manufactures and lots from both anti-IgG-PE and anti-HBSAg-PE conjugates. Coefficients of variation (CVs) showed that this parameter can be used to determine better coupling conditions, such as homogenous coupling. The MESF analysis, as well as geometric mean evaluation by traditional flow cytometry, showed a decrease in the values for all conjugates during the study and were indispensable tools to validate the results of stability tests. Our data demonstrated the feasibility of the flow cytometric method as a standard quality control of immunoassay kits., Competing Interests: The authors have declared that no competing interests exist.

The aim of the present study was to compare the potency and safety of vaccines against Clostridium botulinum (C. botulinum) type C and D formulated with chitosan as controlled release matrix and vaccines formulated in conventional manner using aluminum hydroxide. Parameters were established for the development of chitosan microspheres, using simple coacervation to standardize the use of this polymer in protein encapsulation for vaccine formulation. To formulate a single shot vaccine inactivated antigens of C. botulinum type C and D were used with original toxin titles equal to 5.2 and 6.2 log LD50/ml, respectively. For each antigen a chitosan based solution of 50 mL was prepared. Control vaccines were formulated by mixing toxoid type C and D with aluminum hydroxide [25% Al(OH) 3 , pH 6.3]. The toxoid sterility, innocuity and potency of vaccines were evaluated as stipulated by MAPA-BRASIL according to ministerial directive no. 23. Encapsulation efficiency of BSA in chitosan was 32.5-40.37%, while that the encapsulation efficiency to toxoid type C was 41,03% (1.94 mg/mL) and of the toxoid type D was 32.30% (1.82 mg/mL). The single shot vaccine formulated using chitosan for protein encapsulation through simple coacervation showed potency and safety similar to conventional vaccine currently used in Brazilian livestock (10 and 2 IU/mL against C. botulinum type C and D, respectively). The present work suggests that our single shot vaccine would be a good option as a cattle vaccine against these C. botulinum type C and D., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

UV radiation is a spread method used worldwide for the disinfection of water. However, much of the research on the disinfection of bacterial cells by UV has focused on planktonic cells. Many bacterial cells in nature are present in clumps or aggregates, and these aggregates, which are more resistant to disinfection than their planktonic counterparts, can be problematic in engineered water systems. The current research used Pseudomonas putida (P. putida) CP1, an environmental and non-pathogenic microorganism which autoaggregates when grown under certain conditions, as a model organism to simulate aggregated cells. The study investigated the response of both the planktonic and the aggregated forms of the bacterium to UV-C (λ = 253.7 nm) and UV-A/B (λ > 300 nm) disinfection at laboratory scale in a minimal medium. The planktonic cells of P. putida CP1 were inactivated within 60 s by UV-C and in 60 min by UV-A/B; however, the aggregated cells required 120 min of UV-C treatment and 240 min of UV-A/B radiation to become inactive. The size of the aggregate was reduced following UV treatment. Although all the cells had lost culturability, viability as measured by the LIVE/DEAD ® stain and epifluorescence microscopy was not completely lost and the cells all demonstrated regrowth after overnight incubation in the dark.

Schistosomiasis is a debilitating neglected tropical disease, caused by flatworms of Schistosoma genus. The treatment relies on a single drug, praziquantel (PZQ), making the discovery of new compounds extremely urgent. In this work, we integrated QSAR-based virtual screening (VS) of Schistosoma mansoni thioredoxin glutathione reductase (SmTGR) inhibitors and high content screening (HCS) aiming to discover new antischistosomal agents. Initially, binary QSAR models for inhibition of SmTGR were developed and validated using the Organization for Economic Co-operation and Development (OECD) guidance. Using these models, we prioritized 29 compounds for further testing in two HCS platforms based on image analysis of assay plates. Among them, 2-[2-(3-methyl-4-nitro-5-isoxazolyl)vinyl]pyridine and 2-(benzylsulfonyl)-1,3-benzothiazole, two compounds representing new chemical scaffolds have activity against schistosomula and adult worms at low micromolar concentrations and therefore represent promising antischistosomal hits for further hit-to-lead optimization.

Sudden and unexpected death in epilepsy (SUDEP) is the most common type of death among patients with epilepsy. Here, we address the importance of the experimental models in search of the mechanisms underlying SUDEP. Most studies have investigated the cardiovascular responses in animal models of epilepsy. However, there are few proposed SUDEP models in literature. Hypoventilation, apnea, respiratory distress, pulmonary hypertension, autonomic dysregulation and arrhythmia are common findings in epilepsy models. Impairments on adenosinergic and serotonergic systems, brainstem spreading depolarization, seizure-activation of neural substrates related to cardiorespiratory control, altered autonomic control, and mutations on sodium and potassium channels are hypothesis suggested. Overall, current research highlights the evident multifactorial nature of SUDEP, which involves acute and chronic aspects ranging from systemic to molecular alterations. Thus, we are convinced that elucidation and prevention of SUDEP can be achieved only through the interaction between basic and clinical science.

Background: Cold water immersion (CWI) is a technique commonly used in post-exercise recovery. However, the procedures involved in the technique may vary, particularly in terms of water temperature and immersion time, and the most effective approach remains unclear., Objectives: The objective of this systematic review was to determine the efficacy of CWI in muscle soreness management compared with passive recovery. We also aimed to identify which water temperature and immersion time provides the best results., Methods: The MEDLINE, EMBASE, SPORTDiscus, PEDro [Physiotherapy Evidence Database], and CENTRAL (Cochrane Central Register of Controlled Trials) databases were searched up to January 2015. Only randomized controlled trials that compared CWI to passive recovery were included in this review. Data were pooled in a meta-analysis and described as weighted mean differences (MDs) with 95% confidence intervals (CIs)., Results: Nine studies were included for review and meta-analysis. The results of the meta-analysis revealed that CWI has a more positive effect than passive recovery in terms of immediate (MD = 0.290, 95% CI 0.037, 0.543; p = 0.025) and delayed effects (MD = 0.315, 95% CI 0.048, 0.581; p = 0.021). Water temperature of between 10 and 15 °C demonstrated the best results for immediate (MD = 0.273, 95% CI 0.107, 0.440; p = 0.001) and delayed effects (MD = 0.317, 95% CI 0.102, 0.532; p = 0.004). In terms of immersion time, immersion of between 10 and 15 min had the best results for immediate (MD = 0.227, 95% 0.139, 0.314; p < 0.001) and delayed effects (MD = 0.317, 95% 0.102, 0.532, p = 0.004)., Conclusions: The available evidence suggests that CWI can be slightly better than passive recovery in the management of muscle soreness. The results also demonstrated the presence of a dose-response relationship, indicating that CWI with a water temperature of between 11 and 15 °C and an immersion time of 11-15 min can provide the best results.

Background: The genetic diversity of the Brazilian population results from three ethnic groups admixture: Europeans, Africans and Amerindians, thus increasing the difficulty of performing cystic fibrosis (CF) diagnosis. The nasal potential difference (NPD) evaluates the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity. Despite being a useful CF diagnostic test and a biomarker of CFTR-modulator drugs, it is also highly operator dependent. Therefore, it may be difficult to get accurate results and to interpret them. Wilschanski and Sermet scores were proposed to address these issues. This study aimed to evaluate repeatability and diagnostic value of NPD parameters and Wilschanski and Sermet scores in a CF center in Rio de Janeiro., Methods: NPD was performed in 78 subjects. Maximal PD, amiloride response, total chloride response, and Wilschanski and Sermet scores were explored as means (confidence interval, CI). One-way ANOVA was used to compare mean differences and Scheffe test was used to pair-wise comparisons. Repeatability was evaluated by scatter and Bland-Altman plots. The Ethics Committee of the CF Center has approved the study protocol. Parents and adult participants signed an informed consent form., Results: Forty-eight healthy-volunteers, 19 non-CF and 11 CF patients were enrolled in this study. Significant differences were found when comparing CF patients' NPD parameters to the other two groups (P = 0.000). Moreover, no significant differences were found when parameters from non-CF patients were compared with those from healthy volunteers (P > 0.05). The means of NPD parameters and diagnostic scores of each group were in concordance with disease/non-disease conditions. The repeatability data - Wilschanski and Sermet and NPD - allow NPD to be performed in this Brazilian CF Center., Conclusions: The present study gathered consistent data for Bland-Altman plots. The results of Wilschanski and Sermet diagnostic scores suggest that they were concordant with CF/non-CF conditions. More NPD tests should be performed in the Rio de Janeiro CF dynamic cohort to contribute to international NPD validation studies and to provide NPD as a biomarker in Brazil.

Cardiovascular diseases, such as thrombosis and stroke, represent the major cause of disability and death worldwide; and dysfunctions in platelet aggregation and blood coagulation processes are involved. The regular antithrombotic drugs have unsatisfactory results and may produce side effects. Therefore, alternative therapies have been extensively investigated., Objective: The anticoagulant and antiplatelet aggregation potential of a series of six synthetic 1,2,3-triazole derivatives were investigated through in vitro models., Methods: Coagulation tests included the prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) assays, and were performed on a multichannel coagulometer, using human plasma. The platelet aggregation assays were carried out using human platelet-rich-plasma (PRP). Aggregation was initiated by adding ADP or collagen and monitored turbidimetrically on a Whole Blood Aggregometer. Toxicity of derivatives was evaluated on platelets and red blood cells, by measuring the release of lactate dehydrogenase and hemoglobin, respectively. Moreover, theoretical toxicity of derivatives was calculated using the software Osiris® Property Explorer., Results: All the six derivatives tested inhibited, but with different potencies, the plasma coagulation assessed by the PT and TT assays, and also inhibited platelet aggregation of PRP induced by collagen or ADP. The derivatives did not interfere in the aPTT assay and did not affect the viability of platelets or red blood cells. Theoretical studies also revealed that all derivatives will likely to have low toxicity, great pharmacological and oral bioavailability profiles, and a Druglikeness and Drug score similar to some commercial anticoagulant and antiplatelet drugs., Conclusion: 1,2,3-triazoles are potential candidates for molecular modeling of new antithrombotic drugs.

Understanding the mechanisms that influence brain excitability and synchronization provides hope that epileptic seizures can be controlled. In this scenario, non-synaptic mechanisms have a critical role in seizure activity. The contribution of ion transporters to the regulation of seizure-like activity has not been extensively studied. Here, we examined how non-synaptic epileptiform activity (NEA) in the CA1 and dentate gyrus (DG) regions of the hippocampal formation were affected by kainic acid (KA) administration. NEA enhancement in the DG and suppression in area CA1 were associated with increased NKCC1 expression in neurons and severe neuronal loss accompanied by marked glial proliferation, respectively. Twenty-four hours after KA, the DG exhibited intense microglial activation that was associated with reduced cell density in the infra-pyramidal lamina; however, cellular density recovered 7 days after KA. Intense Ki67 immunoreactivity was observed in the subgranular proliferative zone of the DG, which indicates new neuron incorporation into the granule layer. In addition, bumetanide, a selective inhibitor of neuronal Cl(-) uptake mediated by NKCC1, was used to confirm that the NKCC1 increase effectively contributed to NEA changes in the DG. Furthermore, 7 days after KA, prominent NKCC1 staining was identified in the axon initial segments of granule cells, at the exact site where action potentials are preferentially initiated, which endowed these neurons with increased excitability. Taken together, our data suggest a key role of NKCC1 in NEA in the DG., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

The excitability of neuronal networks is strongly modulated by changes in pH. The origin of these changes, however, is still under debate. The high complexity of neural systems justifies the use of computational simulation to investigate mechanisms that are possibly involved. Simulated neuronal activity includes non-synaptic epileptiform events (NEA) induced in hippocampal slices perfused with high-K(+) and zero-Ca(2+), therefore in the absence of the synaptic circuitry. A network of functional units composes the NEA model. Each functional unit represents one interface of neuronal/extracellular space/glial segments. Each interface contains transmembrane ionic transports, such as ionic channels, cotransporters, exchangers and pumps. Neuronal interconnections are mediated by gap-junctions, electric field effects and extracellular ionic fluctuations modulated by extracellular electrodiffusion. Mechanisms investigated are those that change intracellular and extracellular ionic concentrations and are able to affect [H(+)]. Our simulations suggest that the intense fluctuations in intra and extracellular concentrations of Na(+), K(+) and Cl(-) that accompany NEA are able to affect the combined action of the Na(+)/H(+) exchanger (NHE), [HCO(-)(3)]/Cl(-) exchanger (HCE), H(+) pump and the catalytic activity of intra and extracellular carbonic anhydrase. Cellular volume changes and extracellular electrodiffusion are responsible for modulating pH.

Number transcoding (e.g., writing 29 when hearing "twenty-nine") is one of the most basic numerical abilities required in daily life and is paramount for mathematics achievement. The aim of this study is to investigate psychometric properties of an Arabic number-writing task and its capacity to identify children with mathematics difficulties. We assessed 786 children (55% girls) from first to fourth grades, who were classified as children with mathematics difficulties (n = 103) or controls (n = 683). Although error rates were low, the task presented adequate internal consistency (0.91). Analyses revealed effective diagnostic accuracy in first and second school grades (specificity equals to 0.67 and 0.76 respectively, and sensitivity equals to 0.70 and 0.88 respectively). Moreover, items tapping the understanding of place-value syntax were the most sensitive to mathematics achievement. Overall, we propose that number transcoding is a useful tool for the assessment of mathematics abilities in early elementary school., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)