Clinical usability study of a home-based self-administration transcranial direct current stimulation for primary dysmenorrhea: A randomized controlled trial.

This study tested the usability of a home-based self-administration transcranial direct current stimulation (tDCS) device designed specifically for women's health needs. This is a single center triple blinded clinical usability study for a new wireless, Bluetooth-controlled wearable tDCS device for women's health. The study aims to evaluate the usability and effective blinding of a home-based tDCS system. A total of forty-nine women of reproductive age were randomly allocated (1:1) to receive one session of active tDCS (n = 24) or sham tDCS (n = 25) over the motor and dorsolateral prefrontal cortex. Each participant self-administered one 20-minute session without supervision following guidance on a software application alone. The System Usability Scale (SUS) and the Patient Global Impression of Change (PGIC) were used to evaluate the usability of the system. Regardless of sham or active conditions, all users found the system easy to use without the support of researchers. Usability scores were considered to be "excellent" in both groups and no significant difference was found between sham and active groups showing effective blinding of the device (Active group: 93.7 (83.1-97.5); Sham group 90 (86.2-95) p = 0.79) and PGIC (Active group: 2 (1-2.75); Sham group 2 (1-2) p = 0.99) using an unpaired t-test or non-parametric statistical tests accordingly. The new Bluetooth-controlled wearable tDCS device is easy, safe to use and completely controlled by a smartphone app. This device is focused on women's health and will be tested as an alternative treatment for chronic pelvic pain and mood disturbance associated with menstrual cycles in further research.

Unlocking the power of Libidibia ferrea extracts: antimicrobial, antioxidant, and protective properties for potential use in poultry production.

Plant extracts are increasingly recognized as potential prophylactic agents in poultry production due to their diverse bioactive properties. This study investigated the phytochemical and biological properties of Libidibia ferrea (L. ferrea), a plant species native to the Caatinga region of northeastern Brazil. The aim of this study was to identify secondary metabolites and to demonstrate the antimicrobial, antioxidant and protective effects of the plant extract. Three extracts were produced: EHMV, a hydroalcoholic extract from the maceration of pods, and EEMC and EEMV ethanolic extracts from the maceration of peels and pods, respectively, from L. ferrea. High-performance liquid chromatography (HPLC-MS/MS) and atomic absorption spectroscopy (AAS) were used to characterize the metabolites and metals. The antimicrobial activity against Salmonella Galinarum (SG), Salmonella pullorum (SP), Salmonella Heidelberg (SH) and Avian pathogenic Escherichia coli (APEC) was evaluated alone and in combination with probiotic bacteria (Bacillus velenzensis) using agar diffusion and the bactericidal minimum concentration (CBM). The antioxidant potential of the extracts was evaluated in 5 in vitro assays and 6 assays in 3t3 cells. The toxicity of EHMV was tested, and its ability to combat SP infection was demonstrated using a chicken embryo model. The results showed that EHMV exhibited significant antimicrobial activity. The combination of EHMV with BV had synergistic effects, increased antimicrobial activity and induced bacterial sporulation. Composition analysis revealed the presence of 8 compounds, including tannins and phenolic compounds. In vitro antioxidant tests demonstrated that total antioxidant capacity(TAC) activity was increased, and the extract had strong reducing power and notable metal chelating effects. Analysis of 3T3 cells confirmed the protective effect of EHMV against oxidative stress. Toxicity assessments in chicken embryos confirmed the safety of EHMV and its protective effect against SP-induced mortality. EHMV from L. ferrea is rich in proteins and contains essential metabolites that contribute to its antimicrobial and antioxidant properties. When associated with probiotic bacteria such as B. velezensis, this extract increases the inhibition of SH, SG, SP, and APE. The nontoxic nature of EHMV and its protective effects on chicken embryos make it a potential supplement for poultry.

Anodal tDCS over the motor cortex improves pain but not physical function in chronic chikungunya arthritis: Randomized controlled trial.

BACKGROUND: Chikungunya virus (CHIKV) is a globally prevalent pathogen, with outbreaks occurring in tropical regions. Chronic pain is the main symptom reported and is associated with decreased mobility and disability. Transcranial direct current stimulation (tDCS) is emerging as a new therapeutic tool for chronic arthralgia. OBJECTIVE: To evaluate the effectiveness of 10 consecutive sessions of anodal tDCS on pain (primary outcome) in participants with chronic CHIKV arthralgia. Secondary outcomes included functional status, quality of life, and mood. METHODS: In this randomized, double-blind, placebo-controlled trial, 30 participants with chronic CHIKV arthralgia were randomly assigned to receive either active (n = 15) or sham (n = 15) tDCS. The active group received 10 consecutive sessions of tDCS over M1 using the C3/Fp2 montage (2 mA for 20 min). Visual analog scale of pain (VAS), health assessment questionnaire (HAQ), short-form 36 health survey (SF-36), pain catastrophizing scale, Hamilton anxiety scale (HAS), timed up and go (TUG) test, lumbar dynamometry, 30-s arm curl and 2-min step test were assessed at baseline, day 10 and at 2 follow-up visits. RESULTS: There was a significant interaction between group and time on pain (p = 0.03; effect size 95 % CI 0.9 (-1.67 to -0.16), with a significant time interaction (p = 0.0001). There was no interaction between time and group for the 2-minute step test (p = 0.18), but the groups differed significantly at day 10 (p = 0.01), first follow-up (p = 0.01) and second follow-up (p = 0.03). HAQ and SF-36 improved but not significantly. There was no significant improvement in mental health, and physical tests. CONCLUSION: tDCS appears to be a promising intervention for reducing pain in participants with chronic CHIKV arthralgia, although further research is needed to confirm these findings and explore potential long-term benefits. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC): RBR-245rh7.

Effects of photobiomodulation therapy on the functional performance of healthy individuals: a systematic review with meta-analysis.

The aim of this study is to assess the effect of photobiomodulation therapy (PBMT) on functional performance concerning strength, fatigue, and functional capacity in healthy individuals. This systematic review with meta-analysis involved searches on data platforms and active searches of randomized clinical trials, focusing on PBMT as the sole intervention. Primary outcomes assessed included strength, fatigue, and functional capacity. Three reviewers screened studies by title and abstract using Rayyan, and data were extracted using a specific form. Bias risk was assessed using RoB2, and confidence in the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The RevMan was used for meta-analysis. Sixteen studies were included, totaling 340 individuals (183 males and 157 women). Most articles presented a low risk of bias. Variability was observed in device types and application domains, including wavelengths (655-905 nm), power (10-200 nW), energy (0.6-30 J per point), and time (30-100 s per point). PBMT improved fatigue recovery (mean difference: 5.87; 95% CI 3.83, 7.91). There was no enhancement in strength (peak torque: mean difference 12.40; 95% CI -5.55, 30.55; one-repetition maximum test: mean difference 39.97, 95% CI -2.44, 82.38; isometric and isokinetic strength: mean difference 2.77, 95% CI -14.90, 20.44) nor improvement in short-term (mean difference 0.67, 95% CI -0.58, 1.91) and long-term (mean difference 18.44, 95% CI -55.65, 92.54) functional capacity. PBMT may aid in favoring fatigue recovery in healthy individuals; however, there's no evidence to support PBMT enhancing strength or improving functional capacity.

Projetos de lei de enfrentamento à COVID-19 e suarelação com as competências da Agência Nacional de Vigilância Sanitária / Bills addressing COVID-19 and their relation to the rolesof the National Health Surveillance Agency / Los proyectos de ley para combatir el COVID-19y surelación conlas competencias de la Agencia Nacional de Vigilancia Sanitaria

Objetivo: analisar se os projetos de lei relacionados às medidas de enfrentamento à COVID-19 apresentados na Câmara dos Deputados, entre 2020 e 2021, guardavam correlação com as competências atribuídas à Agência Nacional de Vigilância Sanitária (Anvisa)pela Lei nº 9.782 de 1999. Metodologia: coletou-se os dados disponíveis no portal eletrônico da Câmara dos Deputados, utilizando-se os descritores Anvisa e COVID-19 e Anvisa, nos anos de 2020 e 2021, sendo analisados, portanto, 42 projetos de lei que foram divididos em seis grupos. Resultados: verificou-se que os projetos de lei analisados guardavam correlação com as competências da Anvisa e que os temas mais recorrentes foram distribuição, aquisição e/ou importação e registro de produtos sujeitos à vigilância sanitária, portos aeroportos e fronteiras e serviços sujeitos à vigilância sanitária. Conclusão: a Câmara dos Deputados, por meio de seus parlamentares, propôs projetos de lei de interesse nacional relacionados à pandemia. No entanto, nota-se que alguns desses projetos já haviam sido regulados pela Anvisa, por meio de seu poder regulador. É possível aferir ainda que há uma tendência dos parlamentares de atuarem em resposta a problemas que estão em alta nos veículos de imprensa e, na tentativa de garantir celeridade a aquisição dos insumos de combate à COVID-19no contexto da pandemia, os projetos de lei propostos pelos parlamentares reduziram o papel da Anvisa.

Objective: to analyze whether the bills proposed in the Brazilian Chamber of Deputies to combat COVID-19 between 2020 and 2021 are related to the competences assigned to the National Health Surveillance Agency (Anvisa) by Law No. 9,782 of 1999. Methods: data available on the electronic portal of the Chamber of Deputies were collected using the descriptors Anvisaand COVID -19 and Anvisain 2020 and 2021, resulting in 42 bills which wereclassified into six groups.Results: it was found that the bills analyzed were related to Anvisa's responsibilities and that the most recurring topics were the distribution, acquisition and/or importation, and registration of products subject to health surveillance, ports, airports, and borders, and services subject to health surveillance. Conclusion: the deputies have proposed bills of national interest related to the pandemic. However, some of these projects have already been regulated by Anvisa authority. It is possible to confirm that parliamentarians tend to respond to issues that arise in the press media to ensure acquisition of inputs to combatCOVID-19 and thatthe bills proposed by the parliamentarians have limited the role of Anvisa.

Objetivo: analizar si los proyectos de ley relacionados con medidas de combate al COVID-19 presentados en la Cámara de los Diputadosdel Brasil, entre 2020 y 2021, tenían correlación con las competencias atribuidas a la Agencia Nacional de Vigilancia Sanitaria (Anvisa) por la Ley nº 9.782 de 1999. Metodología: se recopilaron los datos disponibles en el portal electrónico de la Cámara de Diputados, utilizando los descriptores Anvisay COVID-19 y Anvisa, en los años 2020 y 2021. Por lo tanto, se analizaron 42 proyectos de ley, que se dividieron en seis grupos. Resultados: se verificó que los proyectos de ley analizados estaban correlacionados con las competencias de Anvisa y que los temas más recurrentes fueron distribución, adquisición y/o importación y registro de productos sujetos avigilancia sanitaria;puertos, aeropuertos y fronteras;y servicios sujetos a vigilancia sanitaria. Conclusión: los diputados de la Cámara de Diputados presentaronproyectos de ley de interés nacional relacionados con la pandemiayse observóque algunos de estos proyectos ya habían sido regulados por la Anvisa. También es posible verificar que existe una tendencia de los parlamentarios a actuarpara responder a problemas que van en aumento en los medios de prensay, en un intento de asegurar la pronta adquisición de insumos para combatir el COVID-19 en el contexto de la pandemia, los proyectos de ley propuestos por los parlamentarios redujeron el papel de la Anvisa.

Increased Trypanosoma cruzi Growth during Infection of Macrophages Cultured on Collagen I Matrix.

The interactions between cell and cellular matrix confers plasticity to each body tissue, influencing the cellular migratory capacity. Macrophages rely on motility to promote their physiological function. These phagocytes are determinant for the control of invasive infections, and their immunological role largely depends on their ability to migrate and adhere to tissue. Therefore, they interact with the components of the extracellular matrix through their adhesion receptors, conferring morphological modifications that change their shape during migration. Nevertheless, the need to use in vitro cell growth models with the conditioning of three-dimensional synthetic matrices to mimic the dynamics of cell-matrix interaction has been increasingly studied. This becomes more important to effectively understand the changes occurring in phagocyte morphology in the context of infection progression, such as in Chagas disease. This disease is caused by the intracellular pathogen Trypanosoma cruzi, capable of infecting macrophages, determinant cells in the anti-trypanosomatid immunity. In the present study, we sought to understand how an in vitro extracellular matrix model interferes with T. cruzi infection in macrophages. Using different time intervals and parasite ratios, we evaluated the cell morphology and parasite replication rate in the presence of 3D collagen I matrix. Nevertheless, microscopy techniques such as scanning electron microscopy were crucial to trace macrophage-matrix interactions. In the present work, we demonstrated for the first time that the macrophage-matrix interaction favors T. cruzi in vitro replication and the release of anti-inflammatory cytokines during macrophage infection, in addition to drastically altering the morphology of the macrophages and promoting the formation of migratory macrophages.

It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities.

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para-naphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!

Identification of Zika Virus NS1-Derived Peptides with Potential Applications in Serological Tests.

Zika virus (ZIKV), a mosquito-borne pathogen, is an emerging arbovirus associated with sporadic symptomatic cases of great medical concern, particularly among pregnant women and newborns affected with neurological disorders. Serological diagnosis of ZIKV infection is still an unmet challenge due to the co-circulation of the dengue virus, which shares extensive sequence conservation of structural proteins leading to the generation of cross-reactive antibodies. In this study, we aimed to obtain tools for the development of improved serological tests for the detection of ZIKV infection. Polyclonal sera (pAb) and a monoclonal antibody (mAb 2F2) against a recombinant form of the ZIKV nonstructural protein 1 (NS1) allowed the identification of linear peptide epitopes of the NS1 protein. Based on these findings, six chemically synthesized peptides were tested both in dot blot and ELISA assays using convalescent sera collected from ZIKV-infected patients. Two of these peptides specifically detected the presence of ZIKV antibodies and proved to be candidates for the detection of ZIKV-infected subjects. The availability of these tools opens perspectives for the development of NS1-based serological tests with enhanced sensitivity regarding other flaviviruses.

Developing Pharmacological Therapies for Atrial Fibrillation Targeting Mitochondrial Dysfunction and Oxidative Stress: A Scoping Review.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

Pulmonary Fibrosis and Hypereosinophilia in TLR9-/- Mice Infected by Cryptococcus gattii.

Cryptococcus gattii is a worldwide-distributed basidiomycetous yeast that can infect immunocompetent hosts. However, little is known about the mechanisms involved in the disease. The innate immune response is essential to the control of infections by microorganisms. Toll-like receptor 9 (TLR9) is an innate immune receptor, classically described as a non-methylated DNA recognizer and associated with bacteria, protozoa and opportunistic mycosis infection models. Previously, our group showed that TLR9-/- mice were more susceptible to C. gattii after 21 days of infection. However, some questions about the innate immunity involving TLR9 response against C. gattii remain unknown. In order to investigate the systemic cryptococcal infection, we evaluated C57BL/6 mice and C57BL/6 TLR9-/- after intratracheal infection with 104C. gattii yeasts for 21 days. Our data evidenced that TLR9-/- was more susceptible to C. gattii. TLR9-/- mice had hypereosinophilia in pulmonary mixed cellular infiltrate, severe bronchiolitis and vasculitis and type 2 alveolar cell hyperplasia. In addition, TLR9-/- mice developed severe pulmonary fibrosis and areas with strongly birefringent fibers. Together, our results corroborate the hypothesis that TLR9 is important to support the Th1/Th17 response against C. gattii infection in the murine experimental model.

Structure-Based Identification of Naphthoquinones and Derivatives as Novel Inhibitors of Main Protease Mpro and Papain-like Protease PLpro of SARS-CoV-2.

The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In this study, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC50) values between 0.41 µM and 9.0 µM. In addition, three compounds inhibited PLpro with IC50 ranging from 1.9 µM to 3.3 µM. To verify the specificity of Mpro and PLpro inhibitors, our experiments included an assessment of common causes of false positives such as aggregation, high compound fluorescence, and inhibition by enzyme oxidation. Altogether, we confirmed novel classes of specific Mpro and PLpro inhibitors. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.

Nitrogen balance and efficiency as indicators for monitoring the proper use of fertilizers in agricultural and livestock systems.

The rational use of nutrients is a key factor for the sustainability of agricultural systems. This study aimed to analyze the nitrogen balance and use efficiency, and the valorization of organic residues within integrated systems, in comparison to conventional agricultural and livestock systems. The experiment was assembled in a randomized blocks design with three replicates. Six production systems were compared, grain maize production (CROP) and pasture for beef cattle production (LS), and four ICLS (Integrated Crop-Livestock System) for grain maize and pastures for beef cattle, in 2 years. In order to estimate the nutrients balance, inputs, and outputs at farm levels were considered, and with the results obtained for nutrient balance, the use efficiency was calculated. The CROP presented higher nutrient use efficiency (1.43 kg/ha-1), but at the same time, it resulted in negative contributions for the nutrient balance (-97 kg/ha-1) because of lower amounts of nitrogen in the organic residues (188 kg/ha-1) and lower valuation. The LS and ICLS provided a higher amount of nitrogen (983 kg/ha-1; mean ± 921 kg/ha-1) and valuation of organic residues. The presence of components such as pastures and the animal contribute to a positive production system, while reducing the needs for chemical fertilizers.

Evaluation of the in vivo and in vitro anti-inflammatory activity of a new hybrid NSAID tetrahydropyran derivative.

Evaluate the anti-inflammatory activity in vivo and in vitro of cis-(±)-acetate of 4-chloro-6-(naphtalene-1-yl)-tetrahydro-2H-pyran-2-yl) methyl 2-(2-(2,6-diclorofenylamine) phenyl (LS19). Male Swiss mice were analyzed in the paw edema, ear edema, and air pouch tests, and in vitro COX inhibition, cytotoxicity evaluation, and cytokine and nitric oxide determination tests. The compound showed effect on the carrageenan- and bradykinin-induced paw edema and capsaicin-induced ear edema tests. In addition, the compound was able to inhibit leukocyte migration to decrease the levels of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) and to increase the levels of the anti-inflammatory cytokine IL-10. The compound was also able to reduce levels of TNF-α, IL-6, and nitric oxide in the RAW 264.7 cell line and to inhibit COX activity. LS19 did not induce any significant changes in the viability of RAW 264.7 cells, demonstrating safety for these cell lines. The compound LS19 did not reduce the production of gastric mucus and induced a smaller increase in the extent of gastric lesions than that developed by the administration of diclofenac. In summary, the new compound proved to be safer and it had additional mechanisms compared to diclofenac.

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2.

The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In the present work, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC 50 ) values between 0.41 µM and 66 µM. In addition, eight compounds inhibited PLpro with IC 50 ranging from 1.7 µM to 46 µM. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.

Combination of Aerobic Training and Cocoa Flavanols as Effective Therapies to Reduce Metabolic and Inflammatory Disruptions in Insulin-Resistant Rats: The Exercise, Cocoa, and Diabetes Study.

We aimed to investigate the combined effects of aerobic exercise (EXE) and cocoa flavanol (COCOA) supplementation on performance, metabolic parameters, and inflammatory and lipid profiles in obese insulin-resistant rats. Therefore, 32 male Wistar rats (230-250 g) were fed a high-fat diet and a fructose-rich beverage for 30 days to induce insulin resistance. Next, the rats were randomized into four groups, orally administered placebo solution or COCOA supplementation (45 mg·kg-1), and either remained sedentary or were subjected to EXE on a treadmill at 60% peak velocity for 30 min, for 8 weeks. Blood samples and peripheral tissues were collected and processed to analyze metabolic and inflammatory parameters, lipid profiles, and morphological parameters. Supplementation with COCOA and EXE improved physical performance and attenuated body mass gain, adipose index, and adipocyte area. When analyzed as individual interventions, supplementation with COCOA and EXE improved glucose intolerance and the lipid profile reduced the concentrations of leptin, glucose, and insulin, and reduced homeostasis assessment index (all effects were p < .001 for both interventions), while ameliorated some inflammatory mediators in examined tissues. In skeletal muscles, both COCOA supplementation and EXE increased the expression of glucose transporter (p < .001 and p < .001), and combined intervention showed additive effects (p < .001 vs. COCOA alone or EXE alone). Thus, combining COCOA with EXE represents an effective nonpharmacological strategy to treat insulin resistance; it could prevent Type 2 diabetes mellitus by improving physical performance, glucose metabolism, neuroendocrine control, and lipid and inflammatory mediators in the liver, pancreas, adipose tissue, and skeletal muscle in obese male insulin-resistant rats.

Evaluation of the systemic and spinal antinociceptive effect of a new hybrid NSAID tetrahydropyran derivative.

Pain is responsible for inducing physical and mental stress, interfering negatively in patients' quality of life. Classic analgesic drugs, such as opioids and non-steroidal anti-inflammatory drugs, are known for their wide range of adverse effects, making it important to develop new drugs. Thus, this study aimed to analyse the action of the hybrid compound cis- (±) -acetate of 4-chloro-6- (naphthalene-1-yl) -tetrahydro-2h-pyran -2-yl) methyl2- (2- [2,6-dichlorophenylamine] phenyl (LS19) under acute nociceptive conditions, and deepened the understanding of the responsible mechanisms. Male Swiss mice were evaluated in the acetic acid-induced abdominal writhing, formalin, tail flick, capsaicin- and glutamate-induced nociception, thermal stimulation in animals injected with capsaicin and rotarod tests besides the acute and subchronic toxicological evaluation. The compound showed effect on the acetic acid-induced abdominal writhing, formalin (both phases), tail flick, thermal stimulation in animals injected with capsaicin and capsaicin-induced nociception tests. In the study of the mechanism of action was observed reversion of the antihyperalgesic effect of the compound from the previous intraperitoneal and intrathecal administration of naloxone, nor-binaltorphimine, naltrindole, methylnaltrexone, 7-nitroindazole, L-NAME, ODQ, glibenclamide on the tail flick test. In the thermal stimulation in animals injected with capsaicin, the compound showed antinociceptive effect by oral and intraplantar routes, besides to reducing the levels of TNF-α, IL-1ß and PGE2 in the paws previously administered with capsaicin. There were no signs of acute and subchronic intoxication with the compound. In summary, the compound LS19 presented spinal and local antihyperalgesic effect, demonstrating participation of the opioid/NO/cGMP/K+ ATP pathway and TRPV1 receptors and it demonstrated safety in its use in mice.

Coparentalidade e paternidade após o divórcio: experiências de pais e mães separados(as) / Coparenting and paternity after divorce: the perspective of separated fathers and mothers

As repercussões do divórcio perpassam as relações coparentais e a paternidade. O presente estudo buscou compreender e refletir sobre as experiências de pais e mães separados(as) sobre a coparentalidade e o envolvimento do pai com os(as) filhos(as) após a dissolução conjugal. Participaram 12 indivíduos separados(as) que tinham filhos(as) pequenos(as), em dois grupos focais, sendo um composto com seis mulheres/mães e o outro com seis homens/pais. Os dados foram analisados através da análise categorial temática, utilizando-se do software Atlas.ti 5.0 para organização dos dados. A análise dos relatos fez emergir quatro categorias temáticas: repercussões do divórcio na coparentalidade e na paternidade; repercussões da relação coparental no desenvolvimento dos(as) filhos(as); (des)acordos coparentais após o divórcio; recasamento, paternidade e os cuidados aos filhos(as). Os resultados evidenciaram os desafios e a complexidade dos (re)arranjos necessários no pós-divórcio e a interdependência de aspectos individuais, relacionais, contextuais, sociais e culturais para todos os membros da família.

The repercussions of divorce permeate coparental relationships and paternity. The present study sought to understand and reflect on the experiences of separated fathers and mothers on coparenting and the father's involvement with the children after the marital dissolution. A total of 12 separated individuals with young children participated in two focus groups, one composed of six women/mothers and the other of six men/parents. The data were analyzed through thematic categorical analysis using the Atlas.ti 5.0 software to organize the data. The analysis of the reports revealed four thematic categories: repercussions of divorce on coparenting and paternity; repercussions of the coparental relationship on the development of children; coparental (dis)agreements after divorce; remarriage, paternity, and childcare. The results showed the challenges and complexity of the (re)arrangements required in post-divorce and the interdependence of individual, relational, contextual, social, and cultural aspects for all family members.

As contribuições do pensamento sistêmico nos estudos sobre paternidade / The contributions of systemic thinking in studies on paternity

Há um crescente interesse pela relação pai-filho, visto que na sociedade contemporânea, a figura paterna está, gradativamente, conquistando espaços significativos no contexto familiar. No âmbito científico, entre as vertentes teórico-epistemológicas que fundamentam as pesquisas nacionais e internacionais, sobre o tema da paternidade, vem ganhando destaque no campo epistemológico o pensamento sistêmico. Desse modo, o presente artigo tem como objetivo realizar considerações sobre as pesquisas, cujo objeto é a paternidade, pautadas no pensamento sistêmico. O ponto de partida é o entendimento de que o pai é um ser inter-relacional, o que permite diferentes modos de produzir conhecimento sobre a paternidade com base nos pressupostos sistêmicos da complexidade, instabilidade e intersubjetividade.

Interest in the father-son relationship is growing since, in contemporary society, the father figure is conquering significant spaces in the family context. In the scientific field, among the theoretical-epistemological aspects that underlie national and international research on paternity, systemic thinking has gained prominence in the epistemological field. Thus, this article aims to consider research, whose object is paternity, based on systemic thinking. The starting point is the understanding that the father is an interrelational being, which allows different ways to produce knowledge about fatherhood from the systemic assumptions of complexity, instability, and intersubjectivity.

Famílias no pós-divórcio: envolvimento paterno e guarda dos(as) filhos(as) na perspectiva de pais e mães divorciados / Families in post-divorce: paternal involvement and custody of children from the perspective of divorced mothers and fathers

Os (re)arranjos familiares são necessários no contexto pós-divórcio, a fim de preservar os vínculos entre pai, mãe e filhos(as). Este estudo de abordagem qualitativa teve como objetivo caracterizar o envolvimento do pai com os filhos(as) após o término da conjugalidade de acordo com a modalidade de guarda, na perspectiva de pais e mães divorciados(as). Participaram 12 pessoas, as quais haviam se divorcidado quando os(as) filhos(as) estavam na primeira infância. Os pais e mães que não eram membros do mesmo (ex)casal conjugal. Foram realizados dois grupos focais, sendo um composto com seis mulheres/mães e o outro com seis homens/pais. Os dados foram analisados por meio da análise categorial temática, utilizando-se do software Atlas.ti 5.0 para organização dos dados. Os resultados foram organizados em três categorias temáticas: envolvimento paterno, os desdobramentos de pais com guarda compartilhada; o envolvimento paterno de pais “visitantes”, as implicações da guarda unilateral materna e; percepções sobre modalidades de convivência e pensão alimentícia. Este estudo pretende contribuir com o avanço das pesquisas sobre o envolvimento paterno no contexto do divórcio e demarca a importância da guarda compartilhada, como um fator de proteção para o engajamento do pai com os(as) filhos(as), devendo ser incentivada sempre que for possível. Considerando que a guarda compartilhada pode ser determinada em juízo, mesmo nos casos em que há conflitos entre os ex-cônjuges, revela-se a importância do apoio psicológico a pais e mães no período de transição para o divórcio, visando ajudá-los a lidar com aspectos emocionais e relacionais.(AU)

Family (re)arrangements are necessary for the post-divorce context to preserve the bonds between the father, the mother, and the children. This qualitative approach study aimed to characterize the father's involvement with the children after the end of the conjugal relationship under the perspective of divorced parents. Twelve people participated, who had divorced when their children were in early childhood. Fathers and mothers were not members of the same (ex) marital couple. Two focus groups were carried out, one with six women/mothers and the other with six men/fathers. The data were analyzed through themed categorical analysis using the Atlas.ti 5.0 software to organize the data. The results were organized into three themed categories: paternal involvement, the developments of fathers with shared custody; the paternal involvement of “visiting” fathers, the implications of maternal unilateral custody and; perceptions about living arrangements and alimony. This study aims to contribute to the advancement of research on paternal involvement in the context of divorce and highlights the importance of shared custody as a protective factor for the father's engagement with his children which should be encouraged whenever possible. Considering that shared custody can be determined in court, even in cases where there are conflicts between ex-spouses, the importance of psychological support to fathers and mothers in the transition to divorce is clear in order to help them cope with emotional and relational aspects.(AU)

X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection.

Cryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.