GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation.

We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABAA receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception.

Biodegradable Electrospun Conduit with Aligned Fibers Based on Poly(lactic-co-glycolic Acid) (PLGA)/Carbon Nanotubes and Choline Bitartrate Ionic Liquid.

Functionally active aligned fibers are a promising approach to enhance neuro adhesion and guide the extension of neurons for peripheral nerve regeneration. Therefore, the present study developed poly(lactic-co-glycolic acid) (PLGA)-aligned electrospun mats and investigated the synergic effect with carbon nanotubes (CNTs) and Choline Bitartrate ionic liquid (Bio-IL) on PLGA fibers. Morphology, thermal, and mechanical performances were determined as well as the hydrolytic degradation and the cytotoxicity. Results revealed that electrospun mats are composed of highly aligned fibers, and CNTs were aligned and homogeneously distributed into the fibers. Bio-IL changed thermal transition behavior, reduced glass transition temperature (Tg), and favored crystal phase formation. The mechanical properties increased in the presence of CNTs and slightly decreased in the presence of the Bio-IL. The results demonstrated a decrease in the degradation rate in the presence of CNTs, whereas the use of Bio-IL led to an increase in the degradation rate. Cytotoxicity results showed that all the electrospun mats display metabolic activity above 70%, which demonstrates that they are biocompatible. Moreover, superior biocompatibility was observed for the electrospun containing Bio-IL combined with higher amounts of CNTs, showing a high potential to be used in nerve tissue engineering.

Synergism between molecules derived from Garcinia brasiliensis and antimicrobial drugs on field isolates of Mycoplasma hyopneumoniae.

Mycoplasma hyopneumoniae (M. hyopneumoniae) is one of the smallest free-living bacteria found in nature; it has an extremely small genome and lacks a cell wall. It is the main etiological agent of porcine enzootic pneumonia (EP), a chronic respiratory disease with worldwide distribution that causes significant losses in swine production. Due to the great economic impact caused by EP, new strategies for treating and controlling this agent are researched. The objective of this study was to verify the anti-M. hyopneumoniae activity of compounds derived from Garcinia brasiliensis and the synergism with the main antimicrobials used in the treatment of EP; this is the first study assessing the synergism between bioactive molecules and antimicrobial compounds in vitro against isolates of M. hyopneumoniae. The minimum inhibitory concentrations (MICs) of the antimicrobials tiamulin, valnemulin, and enrofloxacin, as well as the bioactive compounds guttiferone-A (Gut-A), 7-epiculsone (7-Epic), copper 7-epiculsone (7-Epic-Cu), and benzophenone, were determined. Subsequently, the interactions of antibiotics with the compounds were evaluated using the checkerboard method. Three field M. hyopneumoniae isolates were used, and the J strain was used as a control. The MIC values of the antimicrobials compared to the field isolates were equal to and lower than those of the reference strain J. Among the compounds used, 7-Epic-Cu showed the lowest MIC value. Synergistic association was observed for Gut-A with tiamulin and valnemulin, whereas 7-Epic and 7-Epic-Cu showed synergistic action with enrofloxacin. No synergistic effect was observed for benzophenone. Despite being an initial study, the results suggest that these combinations hold promise for the treatment of infections caused by M. hyopneumoniae.

Fatigue and resilience in Master's and PhD students in the Covid-19 pandemic in Brazil: A cross-sectional study.

The aim of this study was to analyze levels of fatigue and resilience of Brazilian graduate students during the COVID-19 pandemic and to determine whether there is an association between fatigue and resilience and sociodemographic and academic factors. Data were analyzed using descriptive and inferential statistics, and it was discovered that the variables associated with higher levels of resilience were age; having children; being retired; receiving income above five minimum wages; having had greater problems in other phases of the research schedule; coming from private universities; being from the north of Brazil; studying the area of Health; and having their research schedule unaffected during the pandemic. On the other hand, lack of resilience was associated with not having children; being less well-off financially; being younger; being a woman; studying in a public university; and having to postpone part of the research during the pandemic. The conclusion of the study indicated the need for graduate programs to design strategies to deal with fatigue and promote resilience in Master's and PhD students.

Boolean model of the gene regulatory network of Pseudomonas aeruginosa CCBH4851.

Introduction: Pseudomonas aeruginosa infections are one of the leading causes of death in immunocompromised patients with cystic fibrosis, diabetes, and lung diseases such as pneumonia and bronchiectasis. Furthermore, P. aeruginosa is one of the main multidrug-resistant bacteria responsible for nosocomial infections worldwide, including the multidrug-resistant CCBH4851 strain isolated in Brazil. Methods: One way to analyze their dynamic cellular behavior is through computational modeling of the gene regulatory network, which represents interactions between regulatory genes and their targets. For this purpose, Boolean models are important predictive tools to analyze these interactions. They are one of the most commonly used methods for studying complex dynamic behavior in biological systems. Results and discussion: Therefore, this research consists of building a Boolean model of the gene regulatory network of P. aeruginosa CCBH4851 using data from RNA-seq experiments. Next, the basins of attraction are estimated, as these regions and the transitions between them can help identify the attractors, representing long-term behavior in the Boolean model. The essential genes of the basins were associated with the phenotypes of the bacteria for two conditions: biofilm formation and polymyxin B treatment. Overall, the Boolean model and the analysis method proposed in this work can identify promising control actions and indicate potential therapeutic targets, which can help pinpoint new drugs and intervention strategies.

Use of ergogenic aids among Brazilian athletes: a cross-sectional study exploring competitive level, sex and sports.

Was investigated ergogenic aids (EAs) used by Brazilian athletes and their association with performance, sex, sports classification, and modality. It identified the main purposes of EAs and their prescription. Methods: 239 athletes of 15 modalities, ranging from regional to international level, answered a survey online. Results: Highly competitive athletes consumed nutritional and mechanical aids more (OR = 1.96 CI 95% [1.28-2.9]; OR = 1.79 CI 95% [1.29-2.47]), while the use of psychological EAs decreased [OR = 1.66 95% CI (1.18-2.94); p = 0.001]. Male athletes [OR = 1.44 CI 95% (1.11-2.88)] and individual sports practitioners [OR = 1.78 CI 95% (1.02-3.11)] used nutritional aids more. Triathlon athletes had higher nutritional EA use, while soccer athletes had lower. Combat sports athletes had higher pharmacological EA use. Conclusion: Athletes use nutritional and pharmacological aids more to improve performance and gain lean body mass. Mechanical aids were used for recovery and psychological aids for motivation. Self-prescription is common, especially for pharmacological aids.

Impact of different roasting conditions on the chemical composition, antioxidant activities, and color of Coffea canephora and Coffea arabica L. samples.

This work aimed to evaluate the physicochemical changes during the roasting process of Robusta and Arabica coffee. The highest content of total phenolics was detected in roasted coffee at temperatures of 135 °C/20.20 min, 210 °C/9.02 min, 210 °C/11.01 min, and 220 °C/13.47 min for both species. Robusta coffee showed greater antioxidant activity compared to Arabica coffee, except for the profiles at 230 °C/17.43 min and 275 °C/7.46 min that did not differ between samples by the DPPH and FRAP methods. For Arabica coffee, the antioxidant activity was independent of the roasting profile used. Robusta coffee presented higher values of the indexes b* (intensity of yellow vs blue), c* (chroma) and hue, being characterized as lighter and with greater chroma and hue. The highest levels of caffeoylquinic acid (5-CQA) were observed in Robusta coffee. Arabica coffee had lower trigonelline values. Caffeic acid and hydroxymethylfurfural were identified only in Robusta coffee. However, the results provided solid knowledge for the design of general properties and chemical compounds generated from binomials of roasting time and temperature that are little used in the world market.

Prediction of fluids volume fraction and barium sulfate scale in a multiphase system using gamma radiation and deep neural network.

In the oil industry, during the production of oil and gas, barium sulfate (BaSO4) scale may occur on the inner walls of the pipelines leading to the reduction of the internal diameter, making the fluids' passage difficult and complicating the calculation of the fluids volume fraction. This paper presents a methodology to predict volume fraction of fluids and BaSO4 scale thickness from obtaining spectra of two NaI(Tl) detectors that record the transmitted and scattered beams of gamma-rays. Theoretical models for a multiphase annular flow regime (gas-saltwater-oil-scale) were developed using MCNP6 code, which is a mathematical code based on the Monte Carlo method. The simulated data was used to train a deep neural network (DNN) to predict the volume fraction of gas, saltwater and oil, and the concentric scale thickness. A Python optimization library called Optuna was used for the hyperparameters search to design the DNN architecture. The methodology presented great results, especially for scale thickness prediction. Although the results for saltwater did not reach the same level, it was still possible to predict approximately 70% of the patterns up to 10% relative error. This achievement indicates the possibility to calculate the volume fraction of fluids and the concentric scale thickness in the offshore oil industry using gamma densitometry and deep learning models.

Dengue virus serotype 2 genotype III evolution during the 2019 outbreak in Mato Grosso, Midwestern Brazil.

DENV-2 was the main responsible for a 70% increase in dengue incidence in Brazil during 2019. That year, our metagenomic study by Illumina NextSeq on serum samples from acute febrile patients (n = 92) with suspected arbovirus infection, sampled in 22 cities of the state of Mato Grosso (MT), in the middle west of Brazil, revealed eight complete genomes and two near-complete sequences of DENV-2 genotype III, one Human parvovirus B19 genotype I (5,391 nt) and one Coxsackievirus A6 lineage D (4,514 nt). These DENV-2 sequences share the aminoacidic identities of BR4 lineage on E protein domains I, II and III, and were included in a clade with sequences of the same lineage circulating in the southeast of Brazil in the same year. Nevertheless, 11/34 non-synonymous mutations are unique to three strains inthis study, distributed in the E (n = 6), NS3 (n = 2) and NS5 (n = 3) proteins. Other 14 aa changes on C (n = 1), E (n = 3), NS1 (n = 2), NS2A (n = 1) and NS5 (n = 7) were first reported in a genotype III lineage, having been already reported only in other DENV-2 genotypes. All 10 sequences have mutations in the NS5 protein (14 different aa changes). Nine E protein aa changes found in two sequences, six of which are unique, are in the ectodomain; where the E:M272T change is on the hinge of the E protein at domain II, in a region critical for the anchoring to the host cell receptor. The NS5:G81R mutation, in the methyltransferase domain, was found in one strain of this study. Altogether, these data points to an important evolution of DENV-2 genotype III lineage BR4 during this outbreak in 2019 in MT. Genomic surveillance is essential to detect virus etiology and evolution, possibly related to immune evasion and viral fitness changes leading to future novel outbreaks.

In vitro comparison of the acetylcholinesterase inhibition caused by V- and A-series nerve agents' surrogates.

Nerve agents (NA) pose as a great risk in the modern world. NA from the V-series, such as VX, are currently recognized as the most toxic among those compounds. However, the emergence of new classes of toxicants recently included in the Chemical Weapons Convention (CWC), such as the A-series NA, a class of organophosphorus compounds related to phosphoramidates, pose a new source of concern due to the lack of information. In order advance in the investigation on the toxicity of such toxic chemicals, we performed in vitro studies to compare representatives of the V- and A-series using affordable surrogates. Results suggest a similar inhibition potency between both agents.

Applications of the Near Attack Conformation (NAC) approach in the search for Acetylcholinesterase reactivators.

The Near Attack Conformation (NAC) approach states that the efficiency of an enzyme-catalyzed reaction depends on the prior attainment of optimal conditions for substrate atom organization and positioning for bond formation. These conditions are prerequisites for the transition state (TS) in which the involved atoms are within the van der Waals range of contact and positioned at an angle similar to that achieved after bond formation. The successful application of this approach to investigate the reactivation mechanism of acetylcholinesterase inhibited by nerve agents has contributed to a better understanding of this mechanism and demonstrated consistent corroboration with experimental data. In this article, we summarize the accomplishments achieved thus far and outline future perspectives.

The Effect of Number of Visits, Use of Solvent and Gutta-percha Removal Technique on Postoperative Pain following Nonsurgical Endodontic Retreatment; A Systematic Review and Meta-analysis.

Introduction: The nonsurgical endodontic retreatment (NERT) is the first choice of dental ministration when primary/initial endodontic treatment fails. The present study aimed to investigate the presence of postoperative pain (POP) after NERT in permanent asymptomatic teeth as well as possible factors associated with POP. Materials and Methods: A comprehensive search of literature was performed in Pubmed/MEDLINE, Embase, Scopus and Web of Science databases, up to January 2023; including randomized clinical trials and prospective studies. The risk of bias was assessed with RoB 2.0 and ROBINS-I tools. Subgroups analyses were conducted to evaluate the differences in the incidence or level of POP between the number of visits, the use/not use of solvent, the removal technique of gutta-percha, and the period of POP analysis. Mean differences and confidence intervals (CI) of 95% were used as measures of effect, and meta-regression was used along with subgroup analysis. The certainty of evidence was assessed using GRADE, and the probability value of <0.05 was considered significant. Results: Twenty-four studies were selected, with thirteen included in the meta-analysis. There was a statistical difference between the incidence of POP after 24 h (95% CI, 0.28 to 0.52) and one week (95% CI, 0.02 to 0.13) from the endodontic retreatment (P<0.01). However, there was no statistical difference between different techniques, number of visits and use of solvent (P>0.05) in the same period. In addition, the certainty of evidence was very low. Conclusions: Post-operative pain is a common response to NERT, independent of the retreatment technique(s) applied, number of visits and use of solvent(s); with very low certainty of evidence as well as low risk of bias. Moreover, the current analysis showed a (very) serious risk of inconsistency and imprecision. However, POP was significantly reduced within 1 week of the NERT.

Family Refusal of Heart Valve Donation.

BACKGROUND: Impairment of the heart valves can occur due to many diseases that cause deterioration of the contractile function and harm the body, making it necessary for the heart valves to be transplanted. This study's objective was to analyze families' refusal to donate heart valves between 2001 and 2020. METHODS: This was a cross-sectional study conducted in accordance with the Terms of Family Authorization for Donation of Organs and Tissues from patients diagnosed with brain death by an Organ Procurement Organization in the state of São Paulo. The variables analyzed were sex, age, cause of death, hospital type (private or public), and refusal to donate heart valves. Data analysis was performed using Stata software version 15.0  (StataCorp, LLC, College Station, Tex, United States) in a descriptive and inferential way. RESULTS: A total of 236 people (9.65%) refused to specifically donate heart valves of their relatives, the majority of whom were between 41 and 59 years old. Most potential donors had suffered a stroke and had been in a private hospital. From 2001 to 2009, there was a decreasing trend in males and the age group from 0 to 11 years old, whereas there was an increasing trend in those aged 60 years or older and in the general population. Between 2010 and 2020, there was a downward trend in the 41- to 59-year-old age group and the general population. CONCLUSIONS: The specific refusal to donate heart valves was associated with age, diagnosis, and whether the institution was public or private.

Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2.

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus's invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2. METHODS: The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand's free binding energies using the molecular mechanics - Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD) software.

Identification of the Radiative Parameters-Albedo and Optical Thickness-Of the Juncus maritimus Fiber.

The present work aims to characterize the radiative thermal properties albedo and optical thickness of Juncus maritimus fibers using a FTIR spectrometer. Measurements of normal/directional transmittance and normal and hemispherical reflectance are performed. The numerical determination of the radiative properties is conducted through the computational treatment of the Radiative Transfer Equation (RTE) using the Discrete Ordinate Method (DOM), together with the inverse method, which is done through Gauss linearization. As it is a non-linear system, iterative calculations are necessary, which demand a significant computational cost, and, to optimize this problem, the Neumann method is used for the numerical determination of the parameters. These radiative properties are useful to quantify the radiative effective conductivity.

Radiographic dental age estimation applying and comparing Demirjian's seven (1973) and four (1976) teeth methods.

To apply Demirjian's seven (1973, D7) and four (1976, D4) teeth methods in a sample of Brazilian children and compare their performances for age estimation. Panoramic radiographs of 1200 children (600 females and 600 males) were collected from Southeast Brazil. The children were equally distributed (n = 60 females and 60 males) between age intervals of 1 year between 6 and 15.9 (mean age = 10.9; standard deviation [SD]: 2.9) years. D7 and D4 dental age estimation methods were applied by two observers and were compared based on their error rates (error = estimated age-chronological age). Both methods overestimated the chronological age (p < 0.0001). D7 led to overestimations of 0.71 (p < 0.0001) in females and 0.83 (p < 0.0001) in males, while the overestimations with D4 were 0.14 (p = 0.0067) and 0.73 (p < 0.0001) for females and males, respectively. The mean age estimated by D7 was 11.7 (SD: 3.1) years, while for D4, it was 11.3 (SD: 3.3) years. Intra- and interobserver agreement was ≥ 0.98. D4 optimized the performance of radiographic dental age estimation compared to D7. Improvements were reflected in the total sample and separately for female and male children from Southeast Brazil.

Botryoid embryonal rhabdomyosarcoma of the cervix: A case report.

INTRODUCTION AND IMPORTANCE: Rhabdomyosarcoma (RMS) is a malignant tumor that arises from embryonal skeletal muscle cells. It's responsible for 3 % of cancer cases among children aged from 0 to 14 and 1 % among adolescents and young adults aged from 15 to 19. Embryonal RMS (ERMS) is the most prevalent subtype of rhabdomyosarcoma in the female genital tract. Botryoid sarcomas are a polypoid variant of ERMS. Our objective is to describe the clinical, pathological features and the treatment of a patient diagnosed with RMS botryoid of the cervix. CASE PRESENTATION: We report a case of a 19-year-old female patient diagnosed with botryoid RMS of the cervix. The histopathological evaluation of the cervix showed a polypoid tumor lined by squamous epithelium exhibiting a large hypocellular edematous area. It was classified as group II and stage 1, according to the IRSG multicenter studies. Cervical polypectomy was performed as an oncological surgical treatment and adjuvant chemotherapy consisting of Vincristine 1.5 mg/m2/day and Actinomycin D 0.045 mg/kg/day (VA) for 45 weeks. After 6 months of follow up, she had no evidence of recurrence. CLINICAL DISCUSSION: Cervical ERMS is a rare tumor, especially in adolescence. It's usually presents as a cervical polyp or multiple polyps. Multimodal approaches have remarkably improved the prognosis and decreased the need for radical surgery with its associated morbidity. CONCLUSION: There are a variety of treatment strategies for a rare disease such as cervical botryoid RMS. This case was approached through fertility-conserving surgery, followed by adjuvant chemotherapy and oncological clinical follow up.

Assisting Homeless Women in a City in Brazil during the COVID-19 Pandemic in the Context of a Street Outreach Office: The Perceptions of Health Professionals.

This study aimed to understand the perception of Street Outreach Office professionals regarding the health care offered to homeless women during the COVID-19 pandemic. This is a qualitative and descriptive study developed with nine health professionals of a Street Outreach Office team from a large city in the countryside of São Paulo State (Brazil) from December 2020 to April 2021. Data were obtained through interviews using a semi-structured script with questions about care practices directed to homeless women. The data were analyzed according to content analysis in the thematic modality. Two thematic categories were identified: (i) the reorganization of the Street Outreach Office to meet the demands of the population and (ii) the challenges in caring for homeless women during the pandemic. The activities were intensified with the team's expansion and distribution of supplies such as masks and alcohol-based hand sanitizers. Our findings showed that the primary problem faced was pregnancy during the pandemic. The lack of material and structural resources and social apparatus to care for homeless women was also evidenced. It was possible to conclude that even with all the adversities, the professionals employed creative strategies, contributing, within their limitations, to the care of homeless women.

Exploring electronic, structural and dynamics parameters of phenylbenzothiazole complexes with Mn2+, Cu2+ and Zn2+ for designing new magnetic resonance imaging (MRI) probes: congruence between computation and spectroscopic data.

Cancer is one of the leading causes of human death worldwide, being one of the most serious problems faced by mankind. For the diagnosis, Magnetic Resonance Imaging (MRI), through effective contrast agents (Cas), has greatly helped in the diagnosis at the initial stages. However, it is necessary to include new compounds more effective and selective for cancer diagnosis. The complexes with Mn2+, Cu2+ and Zn2+ have received great attention due to their applications as CAs for MRI. Those materials can shorten the T2 and T2* transverse relaxation times. Thus, the representative structures for hyperfine coupling constants (HFCCs) were selected from docking results by frequency of occupancy calculations. From the Multivariate Analysis to obtain the PCA graphs in the choice of a representative conformations. it is possible to notice that the variable energy does not present a high correlation with the other variables, and structural factors, such as the spatial positions of the metal atoms, seem to be important in the reactivity of the complexes. Structural factors, such as the spatial positions of the metal atoms, seem to be important in the reactivity of the complexes. Theoretical findings suggest that the compounds are capable of increasing the Aiso values of the water molecules, but the complex [Zn(H2O)(NNO)] shows a greater influence, being more sensitive to the Electron paramagnetic resonance parameters than the complexes [CuCl(H2O)NNO] and [MnCl2(H2O)(NNO)] with the explicit solvent and the enzyme. MRI contrast agents have generated various problems due to their high toxicity. In this perspective, this compound may be a promising alternative for transporting the CAs into diseased tissue.Communicated by Ramaswamy H. Sarma.