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Background Transcranial direct-current stimulation (tDCS) has shown promise to decrease fatigue. However, it has never been examined in primary Sjogren Syndrome (pSS). Objective To assess the effect of a tDCS protocol on fatigue in patients with pSS. Methods This is a parallel, double-blind pilot study (NCT04119128). Women aged 18–65 years, with pSS, on stable pharmacological therapy, with complaints of fatigue for at least three months, and with scores >5 on Fatigue Severity Scale (FSS) were included. We randomized 36 participants to receive five consecutive or sham tDCS sessions, with an intensity of 2 mA, for 20 min/day. Results After five tDCS sessions, fatigue severity assessed by the FSS (primary outcome) demonstrated a mean group difference of −0.85 [95% confidence interval (CI) −1.57, −0.13; effect size 0.80] favouring the active group. The active group presented significantly greater reductions in fatigue as measured by the EULAR Sjogren’s Syndrome Patient Reported Index after five tDCS sessions [mean group difference: 1.40; 95%CI -2.33, −0.48; effect size 1.04]. Although there were no between-group differences in the secondary outcomes of sleep, mood and anxiety, within-group comparisons evidenced a small but significant difference in the active group for pain and sleep. There were no significant cortisol changes. All reported adverse events were mild and transitory. Conclusion tDCS seems to be safe and reduce fatigue in pSS. A differential effect on pain and sleep may underlie its effects. Further studies are needed to optimise tDCS treatment strategies in pSS.

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015–2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses., Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories.

SUMMARY The aim of this rapid systematic review is to analyze the prevalence of clinical, socioeconomic, and demographic characteristics, laboratory and imaging findings, diagnostic tests, and treatment information of older adults with COVID-19. To conduct this systematic review, the Cochrane Handbook recommendations will be followed. Patients aged 60 years or older with a confirmed diagnosis of SARS-CoV-2 infection will be included. A comprehensive literature search will be performed in the following databases: MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILACS), Spanish Bibliographic Index on Health Sciences (IBECS) and Epistemonikos COVID-19 L·OVE platform. No language restrictions will be applied. To assess the methodological quality of the included studies and the certainty of the evidence, the Newcastle-Ottawa Scale, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used. The meta-analysis will be performed using R software. We believe this rapid systematic review will be able to summarize the currently available evidence on clinical, socioeconomic characteristics, and management of COVID-19 in older adults. Therefore, it will help implement adequate strategies to fight the pandemic and assist in understanding the clinical profile of older patients with COVID-19, providing data with due scientific support upon which to base future choices of procedures and interventions. RESUMO O objetivo desta rápida revisão sistemática é analisar a prevalência de características clínicas, socioeconômicas e demográficas, achados laboratoriais e de imagem, testes de diagnóstico e informações de tratamento de idosos com COVID-19. Para conduzir esta revisão sistemática, serão seguidas as recomendações do Manual Cochrane. Pacientes com 60 anos ou mais com diagnóstico confirmado de infecção por Sars-CoV-2 serão incluídos. Uma pesquisa bibliográfica abrangente será realizada nas seguintes bases de dados: Medline via PubMed, Embase, Cochrane Central Register of Controlled Trials (Central), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Índice Bibliográfico Espanhol em Ciências da Saúde (Ibecs) e Epistemonikos Plataforma COVID-19 L · OVE. Nenhuma restrição de idioma será aplicada. Para avaliar a qualidade metodológica e a certeza das evidências dos estudos incluídos, serão utilizadas a Escala Newcastle-Ottawa e a abordagem Grading of Recommendations Assessment, Development and Evaluation (Grade). A meta-análise será realizada no software R. Acreditamos que esta revisão sistemática rápida será capaz de resumir as evidências atualmente disponíveis sobre as características clínicas, socioeconômicas e sobre o manejo de idosos com COVID-19. Portanto, ajudará a implementar estratégias adequadas para combater a pandemia e ajudará a entender o perfil clínico de pacientes idosos com COVID-19, fornecendo dados com o devido apoio científico sobre o qual basear futuras escolhas de procedimentos e intervenções.

A alergia alimentar é o nome dado para as reações adversas aos alimentos que circundam mecanismos imunológicos, ocasionando então uma gama de manifestações clínicas. Aproximadamente 6% das crianças com idade inferior a 3 anos, e cerca de 4% dos adultos apresentam desordens alérgicas causadas por alimentos. A alergia alimentar ao trigo (AAT) ocorre quando o sistema imunológico do organismo se torna sensível e reage a qualquer uma das proteínas do trigo. A reação alérgica é classificada conforme o mecanismo imunológico implicado, podendo ser mediada por IgE ou por reações mistas, quando ocorre o envolvimento de citocinas e linfócitos T próinflamatórios, ou imunocomplexos, ou ainda reações citotóxicas. O presente estudo tem por objetivo fazer uma revisão sobre a alergia alimentar ao trigo (AAT), englobando sua manifestação clínica, diagnósticos, e tratamento. A pesquisa de estudos foi feita nas bases de dados de referência Lilacs e Scielo, utilizando os seguintes descritores em saúde: alergia, reação alérgica e trigo. Em relação ao tratamento, o mais eficiente e garantido ainda é a extração absoluta do alérgeno da dieta, no caso do trigo. Diante das considerações, o referido estudo verificou a preocupação frequente quanto ao aumento das alergias alimentares em nível mundial, e salienta-se a importância de novos estudos relacionados ao tratamento dos alérgicos ao trigo no intuito de reduzir as reações alérgicas, manter o estado nutricional, e aumentar a qualidade de vida. Food allergy is the name given to the adverse reactions to foods that surround immunological mechanisms, resulting in a range of clinical manifestations. Wheat allergy develops when the body’s immune system becomes sensitive and reacts immoderately to any of the wheat proteins. Allergic reaction is classified according to the immunological mechanism involved, may be measured by IgE, or by mixed reactions when they occur with the collaboration of mechanisms mediated with cytokines and proinflammatory T-lymphocytes, or by immunocomplexes, or cytotoxic reactions. Approximately 6% of children under the age of 3, and 4% of adults have allergic disorders caused by food. The present study aims to do a revision about food allergy to wheat, including its clinical manifestation, diagnoses and treatment. This monograph was performed in the reference databases Lilacs and Scielo using the following health descriptors: allergy, allergic reaction, and wheat. Regarding the treatment, the most efficient and guaranteed still is the absolute extraction of the allergen from the diet, which in the present case is wheat Taking into account the above considerations, this study verified the frequent concern about the development of food allergies worldwide and concludes the importance of new studies related to the treatment of allergy to wheat to reduce allergic reactions, maintain the nutritional state, and increase the quality of life.

Kefir grains have been applied for milk fermentation, obtaining products derived from kefir fermented milk (kefir, Greek yogurt and whey). During fermentation, proteins become easily digestible and lactose is hydrolyzed, becoming a good option for lactose-intolerant individuals. However, fermentation process can change the essential elements distribution in kefir milk products. Therefore, the aims of the study were to evaluate the total concentration of Ca, Cu, Fe, K, Mg, Mn, Na, P, S and Zn in kefir, whey and Greek yogurt produced with kefir grains inoculated into cow’s milk. Phosphorous was the highest concentration in kefir milk fermented products ranging from 1220 ± 88 μg mL−1 (whey) to 2090 ± 27 μg g−1 (Greek yogurt), whereas Fe was the lowest concentration ranging from 6.7 ± 0.2 μg g−1 (kefir) to 8.9 ± 0.2 μg g−1 (Greek yogurt). Considering the dietary reference intake values, mainly Greek yogurt has proved to be a good source of Ca (21.2%), P (59.7%), and Fe (22.3%).

Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters—including serum interleukin-6 levels—from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.

BACKGROUND: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of infection. OBJECTIVE: To assess whether patients undergoing pharmacological treatment for IMID present higher risk of worse outcomes when diagnosed with COVID-19. DESIGN AND SETTING: Rapid systematic review conducted in the medical school of the Federal University of São Paulo (SP), Brazil. METHODS: We searched CENTRAL, MEDLINE, EMBASE, LILACS, SCOPUS, Web of Science, L·OVE, ClinicalTrials.gov and WHO-ICTRP for studies evaluating patients diagnosed with COVID-19 who were undergoing pharmacological treatment for IMID. Two authors selected studies, extracted data and assessed risk of bias and certainty of evidence, following the Cochrane recommendations. RESULTS: We identified 1,498 references, from which one cohort study was included. This compared patients with and without rheumatic diseases (RD) who all had been diagnosed with COVID-19. Those with RD seemed to have higher chances of hospitalization and mortality, but no statistical difference was detected between the groups: hospitalization: odds ratio (OR) 1.17; 95% confidence interval (CI) 0.6 to 2.29; mortality rate: OR 1.53; 95% CI 0.33 to 7.11 (very low certainty of evidence). Patients with RD were three times more likely to require admission to intensive care units (ICUs), with invasive mechanical ventilation (IMV), than those without RD: OR 3.72; 95% CI 1.35 to 10.26 (for both outcomes; very low certainty of evidence). CONCLUSION: Patients undergoing pharmacological treatment for IMID seem to present higher chances of requiring admission to ICUs, with IMV. Additional high-quality studies are needed to analyze the effects of different treatments for IMID.

To synthesize findings of economic evaluations investigating cost-effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) and of strategies of organization of care related to CPAP therapy. Scoping review with searches conducted in MEDLINE, CRD, LILACS, and Embase in August 2020. Eligible studies were economic evaluations comparing CPAP to other alternative or assessing strategies of care for CPAP therapy. Results were presented narratively, and incremental cost-effectiveness ratios (ICER) were presented in evidence maps. Of 34 studies, 3 concluded that CPAP is less costly and more effective when compared to usual care. Most studies indicated that CPAP is associated with better health outcomes, but at higher prices. ICER ranged from USD 316 to 98,793 per quality-adjusted life years (QALY) gained (median 16,499; IQR 8267 to 33,119). One study concluded that CPAP is more costly and less effective, when treatment is applied to all patients, regardless of disease severity. Variability of ICER was mainly due to definition of population and applied time horizons. When CPAP was compared to mandibular advancement device, ICER ranged from USD 21,153 to 361,028 (median 89,671; IQR 26,829 to 295,983), which represents the investment in CPAP therapy required to obtain one extra QALY. Three studies assessed the effects of organizing CPAP therapy in primary care, which was cost-effective or cost-saving. Compared to usual care, CPAP is cost-effective after the second year of treatment, when indicated for moderate-to-severe OSA. CPAP therapy may be even more cost-effective by using different strategies of organization of care. These findings may inform decision making related to CPAP reimbursement in health systems. Not applicable

BACKGROUND: The numbers of cases of arboviral diseases have increased in tropical and subtropical regions while the coronavirus disease (COVID-19) pandemic overwhelms healthcare systems worldwide. The clinical manifestations of arboviral diseases, especially dengue fever, can be very similar to COVID-19, and misdiagnoses are still a reality. In the meantime, outcomes for patients and healthcare systems in situations of possible syndemic have not yet been clarified. OBJECTIVE: We set out to conduct a systematic review to understand and summarize the evidence relating to clinical manifestations, disease severity and prognoses among patients coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and arboviruses. METHODS: We conducted a rapid systematic review with meta-analysis, on prospective and retrospective cohorts, case-control studies and case series of patients with confirmed diagnoses of SARS-CoV-2 and arboviral infection. We followed the Cochrane Handbook recommendations. We searched EMBASE, MEDLINE, Cochrane Library, LILACS, Scopus and Web of Science to identify published, ongoing and unpublished studies. We planned to extract data and assess the risk of bias and the certainty of evidence of the studies included, using the Quality in Prognosis Studies tool and the Grading of Recommendations Assessment. RESULTS: We were able to retrieve 2,407 citations using the search strategy, but none of the studies fulfilled the inclusion criteria. CONCLUSION: The clinical presentations, disease severity and prognoses of patients coinfected with SARS-CoV-2 and arboviruses remain unclear. Further prospective studies are necessary in order to provide useful information for clinical decision-making processes. Protocol registration number in the PROSPERO database: CRD42020183460

INTRODUCTION: Haemagogus are mosquitoes with diurnal habits that live preferentially in forest areas. In Brazil, they are considered the primary vectors of wild yellow fever. METHODS: The ecological relationships between Haemagogus spegazzinii, the environment, and some of its activities in the semiarid region of Rio Grande do Norte were analyzed by collecting eggs with ovitraps, actively searching in tree holes, capturing adults in Shannon traps, and conducting an investigation for viral infections. RESULTS: A total of 2420 eggs, 271 immature specimens (larvae and pupae), and 206 adults were collected. Egg collection depended on rainfall and relative humidity, with oviposition occurring between January and May. Larvae were found in five plant species, including Tabebuia aurea (craibeira), with 160 larvae collected. We observed shared breeding sites between Hg. spegazzinii and the following species: Aedes albopictus, Aedes terrens, Culex spp., and Toxorhynchites theobaldi. Adults exhibited greater activity between 5 pm and 6 pm, when 191 (92.7%) specimens were captured, while only 1 (0.5%) was collected between 7 pm and 8 pm. The relationship between Hg. spegazzinii and rainfall was significant, with positive correlations with accumulated rainfall 5, 10, 15, 20, and 30 days before mosquito collection. We found that the species was infected with the DENV-2 virus. CONCLUSIONS: This work contributes new information on the bioecology of Hg. spegazzinii, with data on the main reproduction periods, oviposition, breeding sites, activity times, and the relationship between the species and meteorological variables in the Caatinga of northeastern Brazil.

The present study aimed to evaluate the effect of folic acid treatment in an animal model of aging induced by D-galactose (D-gal). For this propose, adult male Wistar rats received D-gal intraperitoneally (100 mg/kg) and/or folic acid orally (5 mg/kg, 10 mg/kg or 50 mg/kg) for 8 weeks. D-gal caused habituation memory impairment, and folic acid (10 mg/kg and 50 mg/kg) reversed this effect. However, folic acid 50 mg/kg per se caused habituation memory impairment. D-gal increased the lipid peroxidation and oxidative damage to proteins in the prefrontal cortex and hippocampus from rats. Folic acid (5 mg/kg, 10 mg/kg, or 50 mg/kg) partially reversed the oxidative damage to lipids in the hippocampus, but not in the prefrontal cortex, and reversed protein oxidative damage in the prefrontal cortex and hippocampus. D-gal induced synaptophysin and BCL-2 decrease in the hippocampus and phosphorylated tau increase in the prefrontal cortex. Folic acid was able to reverse these D-gal-related alterations in the protein content. The present study shows folic acid supplementation as an alternative during the aging to prevent cognitive impairment and brain alterations that can cause neurodegenerative diseases. However, additional studies are necessary to elucidate the effect of folic acid in aging.

Past human societies have left persistent marks on forests worldwide. However, the degree to which pre-colonial Amerindian societies have affected forest structure is still not fully understood, especially in southern Brazil. This study investigated the influence of two distinct Amerindian groups (Southern-Je and Guarani) over tree composition of forest fragments in the State of Santa Catarina. Vegetation data was obtained from the Santa Catarina Forest and Floristic Inventory (SCFFI): a statewide systematic vegetation sampling project. Archaeological data was collated from literature reviews as well as existing databases for archaeological sites occupied by Guarani and Southern-Je groups. Using these sites of known Amerindian occupation, and corresponding environmental variables, ecological niche models were developed for each Amerindian group, predicting potential archaeological sites occupied by these groups across southern Brazil. Maps of these potential occupation sites of pre-colonial Amerindian groups were compared with 417 corresponding floristic inventory plots. Redundancy analysis (RDA) was used to identify floristic composition patterns linked to areas with a high probability of Southern-Je or Guarani presence. Southern-Je and Guarani pre-colonial occupations overlapped near main rivers; however, Southern-Je groups generally occupied elevated areas whereas Guarani occupied mostly coastal areas. We observed differences in forest composition associated with the predicted occurrence of these pre-colonial Amerindian groups. Based on these results, we argue there is a relationship between tree species distribution and pre-colonial human occupation by these two Amerindian groups.

Continuous climate changes associated with the disorderly occupation of urban areas have exposed Latin American populations to the emergence and reemergence of arboviruses transmitted by Aedes aegypti. The magnitude of the financial and political problems these epidemics may bring to the future of developing countries is still ignored. Due to the lack of effective antiviral drugs and vaccines against arboviruses, the primary measure for preventing or reducing the transmission of diseases depends entirely on the control of vectors or the interruption of human-vector contact. In Brazil the first attempt to control A. aegypti took place in 1902 by eliminating artificial sites of eproduction. Other strategies, such as the use of oviposition traps and chemical control with dichlorodiphenyltrichlorethane and pyrethroids, were successful, but only for a limited time. More recently, biotechnical approaches, such as the release of transgenics or sterile mosquitoes and the, development of transmission blocking vaccines, are being applied to try to control the A. aegypti population and/or arbovirus transmission. Endemic countries spend about twice as much to treat patients as they do on the prevention of mosquito-transmitted diseases. The result of this strategy is an explosive outbreak of arboviruses cases. This review summarizes the social impacts caused by A. aegypti-transmitted diseases, mainly from a biotechnological perspective in vector control aimed at protecting Latin American populations against arboviruses.

The rs17782313 variant of the MC4R gene plays an important role in the obesity phenotype. Studies that evaluate environmental factors and genetic variants associated with obesity may represent a great advance in understanding the development of this disease. This work seeks to assess the association of the polymorphism of MC4R rs17782313 on plasma parameters, including leptin, ghrelin, tumor necrosis factor (TNFα) and interleukin 6 (IL6), and on the eating behaviors of morbidly obese women. 70 adult women with BMI between 40 and 60 kg/m2 were recruited. Laboratory and anthropometric data were recorded. Using a visual analog scale (VAS), the feelings of hunger and satiety were evaluated. The presence or absence of binge eating was evaluated through the Binge Eating Scale (BES) questionnaire. Habitual food intake was analyzed using 3-day dietary records. TaqMan® assays were conducted using real-time PCR to assess genotype polymorphism variants from peripheral blood DNA. This study found that female patients with the MC4R rs17782313 polymorphism had high levels of ghrelin and reduced levels of IL6 in the postprandial period. We observed a higher prevalence of severe binge eating in more than 50% of women with at least one risk allele. Our hypothesis is that the MC4R rs17782313 polymorphism may influence the release of ghrelin, even without being associated with feelings of hunger and satiety. More than half of women with this polymorphism exhibited severe binge eating. Level III: case–control analytic study.

Glyphosate (N-phosphonomethyl-glycine) (GLY) is the active ingredient of the most used herbicides in the world. GLY is applied in formulated products known as glyphosate-based herbicides (GBH), which could induce effects that are not predicted by toxicity assays with pure GLY. This herbicide is classified as organophosphorus compound, which is known to induce neurotoxic effects. Although this compound is classified as non-neurotoxic by regulatory agencies, acute exposure to GBH causes neurological symptoms in humans. However, there is no consensus in relation to neurotoxic effects of GBH. Thus, the aim of this study was to investigate the neurotoxic effects of the GBH in the zebrafish Danio rerio, focusing on acute toxicity, the activity and transcript levels of mitochondrial respiratory chain complexes, mitochondrial membrane potential, reactive species (RS) formation, and behavioral repertoire. Adult zebrafish were exposed in vivo to three concentrations of GBH Scout®, which contained GLY in formulation (fGLY) (0.065, 1.0 and 10.0 mg L−1 fGLY) for 7 d, and an in vitro assay was performed using also pure GLY. Our results show that GBH induced in zebrafish brain a decrease in cell viability, inhibited mitochondrial complex enzymatic activity, modulated gene expression related to mitochondrial complexes, induced an increase in RS production, promoted hyperpolarization of mitochondrial membrane, and induced behavioral impairments. Together, our data contributes to the knowledge of the neurotoxic effects of GBH. Mitochondrial dysfunction has been recognized as a relevant cellular response that should not be disregarded. Moreover, this study pointed to the mitochondria as an important target of GBH.

Alzheimer’s disease (AD) is a neurodegenerative disease which is characterized by progressive memory loss, the accumulation of β-amyloid peptide (Aβ) (mainly Aβ1-42), and more recently, by neuroinflammation, which has been highlighted as playing a central role in the development and progress of AD. This study utilized 100-day-old Balb/c mice for the induction of an AD-like dementia model. The animals were administered with Aβ1-42 oligomers (400 pmol/site) or artificial cerebrospinal fluid (ACSF) into the left cerebral ventricle. Twenty-four hours after intracerebroventricular administration, the animals were treated with minocycline (50 mg/kg, via oral gavage) for 17 days. The animals’ locomotion was evaluated using the open-field test. The spatial memory was tested using the Y-maze, and the aversive memory was evaluated using the inhibitory avoidance task. Treatment with minocycline was shown to improve both spatial and aversive memories in mice that were submitted to the dementia model. In addition, minocycline reduced the levels of Aβ and microglial activation in the animals that received the administration of Aβ1-42 oligomers. Moreover, the results suggest that the decrease in microglial activation occurred because of a reduction in the levels of toll-like receptors 2 (TLR2) content, and its adapter protein MyD88, as well as a reduction in the levels of the protein NLRP3, which is indispensable in the assembly of inflammasome. These observations were evaluated via immunohistochemistry and confirmed using the Western blot analysis. Treatment with minocycline had no effect in preventing apoptotic morphologic alterations of the neurons. Thus, the anti-inflammatory effect of minocycline involves TLR2 receptors and NLRP3, besides being beneficial by ameliorating memory impairments.

Background The fat mass and obesity-related (FTO) gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation. Objective The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6), tumor necrosis factor α (TNFα) levels and food intake of morbidly obese women. Materials and methods The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m2. Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction. Results Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFα intragenotypes, it was observed that those with TT had decreased leptin and increased IL6 at the postprandial period. Subjects with TA showed increased postprandial IL6, and those with AA had decreased postprandial ghrelin. There was no difference in TNFα intra- and intergenotypes. The postprandial sensations of hunger were lower in AA than those with TT. There were differences between genotypes regarding ingested grams of protein by weight, cholesterol, B3, B5, B6 and B12 vitamins, and selenium potassium and sodium minerals. Conclusion These findings suggest that genetics may exert an influence on physiologic factors and might alter eating behavior.

Background The tetraprenylated benzophenone 7-epiclusianone (7-epi) is a substance isolated from the fruits of Garcinia brasiliensis and in vitro studies have demonstrated that 7-epi is effective against Schistosoma mansoni adult worms. Hypothesis/Purpose Here we report the in vivo evaluation of 7-epi and its pharmacokinetic in healthy and Schistosoma mansoni infected mice. Study design and methods In this work, we assayed the schistosomicidal activity of 7-epi at the dose of 100 mg/kg and 300 mg/kg body weight/day in S. mansoni experimentally infected mice. Besides, two groups of animals were treated and a detailed analysis of plasma samples was performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS). Results The worm burden showed a reduction in the infected mice after treatment with 300 mg/kg for five days (p Conclusion The results showed significant schistosomicidal in vivo activity at 300 mg/kg. In addition, livers from S. mansoni infected mice showed a greater number of egg granulomas and the changes in the pharmacokinetic parameters in this group could be associated with the pathology of the murine experimental schistosomiasis.

RESUMO Objetivou-se verificar as interações entre a configuração espacial da paisagem, a organização florísticoestrutural e as taxas demográficas do componente arbóreo em um sistema de fragmentos e corredores de Floresta com Araucárias em Lages, Santa Catarina. Para isso, foi elaborado um modelo conceitual das possíveis inter-relações, que foi avaliado pela técnica de Modelagem de Equações Estruturais. No ano de 2010, foram obtidas as métricas da paisagem (área, distância do vizinho mais próximo e relação borda e o interior da floresta) e os dados do primeiro inventário florestal. Foram alocadas parcelas permanentes em cinco fragmentos e corredor florestal, onde todos os indivíduos arbóreos com CAP (circunferência a altura do peito, medida a 1,30 do solo) igual ou superior a 15,7 cm foram identificados e mensurados. Em 2014 foi realizado o segundo inventário, com a inclusão de indivíduos recrutas, contagem de mortos e sobreviventes, e foram calculadas as taxas demográficas. Os dados foram analisados por meio da Análise de Componentes Principais (PCA), Análise de Coordenadas Principais (PCoA), Modelagem de Equações Estruturais e Modelos Lineares Generalizados (GLM). Os resultados demonstraram que a estrutura da paisagem (PCA 1) exerceu influência apenas sobre a organização florístico-estrutural do componente arbóreo, indicada pela distribuição preferencial de espécies arbóreas em função da intensidade da fragmentação. Por sua vez, as taxas demográficas (taxas de ganho e perda em área basal e de mortalidade) foram influenciadas por aspectos estruturais da vegetação (abundância e área basal). Conclui-se que existem variações florísticoestruturais associadas à configuração espacial dos fragmentos na paisagem e que as taxas demográficas apresentam relação com o estágio sucessional da floresta, sintetizado pelas variáveis estruturais de área basal e abundância. ABSTRACT The aim of this study was to investigate the interactions among the landscape spatial configuration, the floristic-structural organization and demographic rates of the tree component of a system of araucaria forest fragments, in Lages, Santa Catarina state. To do so, we developed a conceptual model of inter-relationship that was evaluated by Structural Equation Modeling. In 2010, the landscape metrics (area, distance from the nearest neighbor and edge-core ratio) and first vegetation inventory data were obtained. Permanent plots were allocated in five forest fragments and forest corridor, where all tree individuals with cbh (circumference at breast height, measured at 1.30 ground) greater than or equal to 15.7 cm were identified and measured. In 2014, the second inventory was conducted, with the inclusion of recruits and counting dead and survivor’s individuals, followed by the determination of demographic rates. The data were analyzed through Principal Component Analysis (PCA), Principal Coordinates Analysis (PCoA), Structural Equation Modelling, and Generalized Linear Models (GLM). The results showed that the landscape structure (PCA 1) had a significant influence only on the floristic-structural organization of the tree component, indicated by the preferential distribution of tree species in response to fragmentation intensity. In turn, the demographic rates (basal area gain and loss rates, and mortality rate) were influenced by structural aspects of vegetation (abundance and basal area). We conclude that there was floristic-structural variation associated to the spatial configuration of fragments in the landscape and that the demographics rates presented relation with forest successional stage, synthetized by structural variables of basal area and abundance.

Dengue, zika and chikungunya are arboviruses transmitted by mosquitoes of genus Aedes. In clinical diagnostic routines, cross reactions between dengue and zika may occur because they are viruses of the same family (Flaviviridae); on the other hand, chikungunya is an alphavirus. In this study we suggest the use of FTIR spectroscopy in conjunction with PCA-LDA, SPA-LDA and GA-LDA multivariate classification algorithms as a tool sensitive to biochemical variations caused by the presence of different viruses in the blood. We used 45 blood samples from patients diagnosed with dengue, 30 blood samples from patients diagnosed with zika, 10 samples from patients diagnosed with chikungunya and 45 blood samples from people without these viruses. The objective of the study was to evaluate, mainly, the specificity of the technique in discriminating the blood samples based only on the presence or absence of different viruses and to compare it with some standard diagnostic methods. The results showed sensitivity and specificity values of 100% for the healthy, dengue and chikungunya classes and values close to 90% for zika, suggesting that spectroscopic techniques have great potential for detecting the biochemical variations that the presence of the virus causes in the blood, through a fast methodology.

Objective: To investigate the prevalence of intestinal parasitic infections and the associated risk factors in children attending preschools located in areas with different socioeconomic and structural features in the city of Rondonópolis, State of Mato Grosso, Brazil. Methods: A cross-sectional survey was conducted between 2015 and 2016 among four-to-five years old children. Initially, urban neighborhoods with preschools were classified into five risk strata for parasitic infections, which were defined on the basis of socioeconomic and structural variables. Then, one school from each stratum was randomly chosen for data collection. After obtaining the written informed consent from parents or guardians, the children provided stool samples for examination. Interviews were conducted with parents or guardians to determine the associated risk factors. Results: Coproparasitological tests were performed on 215 (46.5%) preschoolers, and the overall prevalence was 22.8%. The occurrence of such infections increased with the increase in risk stratum of the neighborhood. Protozoa infections, mainly by Entamoeba coli (11.2%) and Giardia duodenalis (9.8%), were the most frequent. The consumption of tap water (OR = 3.56, P = 0.002), no washing of fruits and vegetables before consumption (OR = 3.44, P = 0.002), and no hand washing before eating (OR = 2.63, P = 0.004) were associated with these infections. Conclusions: The prevalence of intestinal parasites among Rondonópolis preschoolers is relevant and associated with precarious hygienic–sanitary behavior, especially in areas with poor socioeconomic and structural conditions.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The main hallmarks of this disease include progressive cognitive dysfunction and an accumulation of soluble oligomers of β-amyloid (Aβ) 1-42 peptide. In this research, we show the effects of lithium and memantine on spatial memory and neuroinflammation in an Aβ1-42 oligomers-induced animal model of dementia in rats. Aβ 1-42 oligomers were administered intrahippocampally to male wistar rats to induce dementia. Oral treatments with memantine (5mg/kg), lithium (5mg/kg), or both drugs in combination were performed over a period of 17days. 14days after the administration of the Aβ1-42 oligomers, the radial arm-maze task was performed. At the end of the test period, the animals were euthanized, and the frontal cortex and hippocampus were removed for use in our analysis. Our results showed that alone treatments with lithium or memantine ameliorate the spatial memory damage caused by Aβ1-42. The animals that received combined doses of lithium and memantine showed better cognitive performance in their latency time and total errors to find food when compared to the results from alone treatments. Moreover, in our study, lithium and/or memantine were able to reverse the decreases observed in the levels of interleukin (IL)-4 that were induced by Aβ1-42 in the frontal cortex. In the hippocampus, only memantine and the association of memantine and lithium were able to reverse this effect. Alone doses of lithium and memantine or the association of lithium and memantine caused reductions in the levels of IL-1β in the frontal cortex and hippocampus, and decreased the levels of TNF-α in the hippocampus. Taken together, these data suggest that lithium and memantine might be a potential therapy against cognitive impairment and neuroinflammation induced by Aβ1-42, and their association may be a promising alternative to be investigated in the treatment of AD-like dementia.

To assess the effects of bilingualism compared to monolingualism on the clinical manifestation of Alzheimer’s Disease. Data from meta-analyses suggest that bilingual individuals exhibit Alzheimer’s Disease symptoms are diagnosed later than monolingual participants. Bilingualism may delay the manifestation of symptoms and diagnosis of Alzheimer’s Disease. To assess the effects of bilingualism compared to monolingualism on the clinical manifestation of Alzheimer’s disease. We searched the databases: MEDLINE, The Cochrane Central Register of Controlled Trials, Embase and LILACS, and searched by hand and in gray literature for studies published before September 2019. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Two reviewers independently searched for studies, extracted data, and performed the quality assessment. Eight studies were included in this review. Data from meta-analyses suggest that bilingual individuals with Alzheimer's disease exhibit symptoms (694 participants; mean difference (MD) (4.05 years; 95% CI: 1.87–6.22 and are diagnosed later (1012 participants; MD 2.0 years; 95% CI: 0.08–3.92) than monolingual participants. Bilingualism may delay the manifestation of symptoms and diagnosis of Alzheimer’s disease. Further studies with more rigorous methodology are needed to improve the precision of the results.

Folic acid (FA) supplementation is important during pregnancy to avoid malformations in the offspring. However, it is unknown if it can affect the offspring throughout their lives. To evaluate the offspring, female mother rats (dams) were separated into 5 groups: Four groups received the AIN-93 diet, divided into control and FA (5, 10, and 50 mg/kg), and an additional group received a FA-deficient diet, and the diet was performed during pregnancy and lactation. We evaluated the female offspring of these dams (at 2 and 18 months old). The aged offspring fed with FA-deficient diet presented habituation, spatial and aversive memory impairment and the FA maternal supplementation prevented this. The natural aging caused an increase in the TNF-α and IL-1β levels in the hippocampus from 18-month-old offspring. FA maternal supplementation was able to prevent the increase of these cytokines. IL-4 levels decreased in the prefrontal cortex from aged control rats and FA prevented it. FA deficiency decreased the levels of IL-4 in the hippocampus of the young offspring. In addition, natural aging and FA deficiency decreased brain-derived neurotrophic factor levels in the hippocampus and nerve growth factor levels in the prefrontal cortex and FA supplementation prevented it. Thus, the present study shows for the first time the effect of FA maternal supplementation on memory, cytokines, and neurotrophins in the aged offspring.

Visceral leishmaniasis (VL), caused by digenetic protozoa of the genus Leishmania, is the most severe form of leishmaniasis. Leishmania infantum is one of the species responsible for VL and the disease caused is considered a zoonosis whose main reservoir is the dog. Canine visceral leishmaniasis (CVL) can lead to the death of the animal if left untreated. Furthermore, the available pharmocologial treatment for CVL presents numerous disadvantages, such as relapses, toxicity, drug resistance, and the fact treated animals continue to be reservoirs when treatment fails to achieve parasitological cure. Moreover, the available VL control methods have not been adequate when it comes to controlling parasite transmission. Advances in immune response knowledge in recent years have led to a better understanding of VL pathogenesis, allowing new treatments to be developed based on immune system activation, often referred to as immunotherapy. In fact, well-defined protocols have been described, ranging from the use of immunomodulators to the use of vaccines. This treatment, which can also be associated with chemotherapy, has been shown to be effective in restoring or inducing an adequate immune response to reduce parasitic burden, leading to clinical improvement. This review focuses on immunotherapy directed at dogs infected by L. infantum, including a literature review of what has already been done in dogs. We also introduce a promising strategy to improve the efficacy of immunotherapy.

Background Fibromyalgia is a heterogeneous condition that appears to be associated with physiological and biochemical disturbances of pain modulation, and that consequently affects numerous other facets of life. Tramadol is currently being explored as an option to manage fibromyalgia pain and other symptoms because of its inhibitory activity of reuptake of neurotransmitters, but its safety and efficacy have not yet been established in these patients. Objective To evaluate the effectiveness and safety of tramadol on the management of symptoms of the syndrome. Methods We searched CENTRAL, MEDLINE, EMBASE, LILACS, Opengrey, ClinicalTrials.gov and WHO-ICTRP for randomised controlled trials analysing the association between tramadol used for fibromyalgia either single-agent or in combination with other drugs. Two reviewers independently extracted data and assessed risk of bias using the Cochrane risk-of-bias tool for all included studies. Quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results Four RCTs comprising 459 patients were included. Tramadol-either as a single-agent or in combination with an antidepressant or analgesic-had a positive effect on pain. Tramadol combined with analgesic showed improved quality of life over placebo as measured by the Fibromyalgia Impact Questionnaire at 91 days. However, this difference did not hold for tramadol as a single agent against placebo. The evidence in these articles was rated "low" using the GRADE approach. No serious adverse events were reported. No improvement in depression and quality of sleep were observed. Conclusions This systematic review found a dearth of clinical trials on tramadol in patients with fibromyalgia. Although the combination of monoamine and opioid mechanism of tramadol has shown positive effects for fibromyalgia, the available evidence is not sufficient to support or refute the use of tramadol in clinical practice for pain or symptom management. Protocol registration number in the PROSPERO database: CRD42017062139.

Objective Shoulder pain and dysfunction are highly prevalent after neck dissection in the treatment of head and neck cancer (HNC). They can lead to muscle weakness, limited range of motion, and shoulder tilt and pain, which can reduce patient functioning. The purpose of this study was to evaluate the effectiveness of rehabilitation interventions for shoulder dysfunction in patients with surgically treated HNC. Methods A search of principal databases (MEDLINE, Embase, CENTRAL, LILACS, IBECS, PEDro, and SciELO) was conducted, in addition to hand searches and a search of gray literature, for all randomized clinical trials (RCTs) published before February 2020. Two authors independently selected all relevant studies. The 7 RCTs fulfilling all inclusion and exclusion criteria were assessed for risk of bias and certainty of evidence using the Cochrane Collaboration risk-of-bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, respectively. Results Moderate-certainty evidence suggests that progressive resistance training is better than conventional treatment for improving pain and dysfunction in patients with HNC (pooled data from 214 participants; mean difference = −5.92; 95% CI = −11.38 to −0.45). Low-certainty evidence (data from 2 RCTs with 106 participants that could not be combined) suggests that acupuncture seems to be more effective than conventional treatment. Conclusions Progressive resistance training is effective for improving shoulder pain and dysfunction in patients with HNC. Further high-quality RCTs are needed to examine the effectiveness of acupuncture for improving shoulder pain and dysfunction in these patients. Future studies with longer follow-up times are needed to clarify the effects of early postoperative intervention. Impact Clinicians can have confidence that progressive resistance training in patients with surgically treated HNC is effective. Lay Summary These study results show that people with head and neck cancer can benefit from gradually increased resistance training to reduce shoulder pain and improve function. This study will help researchers design clinical trials to determine whether treatments such as acupuncture and early physical therapy also could be effective in treating this population.

As Doenças Inflamatórias Intestinais (DII) se caracterizam pela inflamação do trato gastrointestinal e os dois tipos mais comuns são: doença de Crohn (DC) e Retocolite Ulcerativa (RCU). Ambas as doenças têm por característica a ativação imune recidivante. Dentro desse contexto, a melatonina (MLT), um indol formado enzimaticamente a partir do L-triptofano, tem se mostrado como um hormônio versátil favorável no tratamento da doença DII. Diante das principais complicações associadas a DII, o objetivo da presente revisão integrativa foi levantar os principais achados científicos relacionados ao uso da MLT no tratamento da DC e RCU. Para tanto, foi realizada uma revisão integrativa considerando-se bibliografias selecionadas nas principais bases de dados. A MLT parece desempenhar papel importante no TGI, considerando efeitos relacionados a regulação da motilidade gastrointestinal, eliminação de radicais livres, atividade anti-inflamatória local, bem como a moderação da sensação visceral. Assim, parece ser uma alternativa promissora no tratamento das DII.

BACKGROUND: Telemedicine has emerged as a tool for overcoming the challenges of healthcare systems and is likely to become increasingly viable, since information and communication technologies have become more sophisticated and user-friendly. OBJECTIVE: We aimed to identify all Cochrane systematic reviews (CSRs) on telemedicine within healthcare and to summarize the current evidence regarding its use. DESIGN AND SETTING: Review of CSRs, developed at the Discipline of Emergency and Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. METHODS: We searched for studies that compared use of telemedicine with conventional treatment or management of diseases within healthcare. Diagnostic telemedicine studies or studies using automatic text, voice-text or even self-managed care were excluded. The main characteristics and the certainty of evidence were synthetized and critically discussed by all authors. RESULTS: We included 10 CSRs that investigated a broad range of diseases. There is still insufficient evidence to determine what types of telemedicine interventions are effective, for which patients and in which settings, and whether such interventions can be used as a replacement for the standard treatment. Harm relating to telemedicine technologies needs to be better investigated and addressed. CONCLUSION: Telemedicine might be an excellent way to facilitate access to treatment, monitoring and dissemination of important clinical knowledge. However, given the recognition of systematic reviews as the best evidence resource available for decision-making, further randomized controlled trials with stricter methods are necessary to reduce the uncertainties in evidence-based use of telemedicine.

Ticks are considered the most important vectors in veterinary medicine with a profound impact on animal health worldwide, as well as being key vectors of diseases affecting household pets. The leading strategy applied to dog tick control is the continued use of acaricides. However, this approach is not sustainable due to surging tick resistance, growing public concern over pesticide residues in food and in the environment, and the rising costs associated with their development. In contrast, tick vaccines are a cost-effective and environmentally friendly alternative against tick-borne diseases by controlling vector infestations and reducing pathogen transmission. These premises have encouraged researchers to develop an effective vaccine against ticks, with several proteins having been characterized and used in native, synthetic, and recombinant forms as antigens in immunizations. The growing interaction between domestic pets and people underscores the importance of developing new tick control measures that require effective screening platforms applied to vaccine development. However, as reviewed in this paper, very little progress has been made in controlling ectoparasite infestations in pets using the vaccine approach. The control of tick infestations and pathogen transmission could be obtained through immunization programs aimed at reducing the tick population and interfering in the pathogenic transmission that affects human and animal health on a global scale.

D-Galactose (D-gal) chronic administration via intraperitoneal and subcutaneous routes has been used as a model of aging and Alzheimer disease in rodents. Intraperitoneal and subcutaneous administration of D-gal causes memory impairments, a reduction in the neurogenesis of adult mice, an increase in the levels of the amyloid precursor protein and oxidative damage; However, the effects of oral D-gal remain unclear. The aim of this study was to evaluate whether the oral administration of D-gal induces abnormalities within the mitochondrial respiratory chain of rats. Male Wistar rats (4 months old) received D-gal (100 mg/kg v.o.), during the 1st, 2nd, 4th, 6th or 8th weeks by oral gavage. The activity of the mitochondrial respiratory chain complexes was measured in the 1st, 2nd, 4th, 6th and 8th weeks after the administration of D-gal. The activity of the respiratory chain complex I was found to have increased in the prefrontal cortex and hippocampus in the 1st, 6th and 8th weeks, while the activity of the respiratory chain complex II increased in the 1st, 2nd, 4th, 6th and 8th weeks within the hippocampus and in the 2nd, 4th, 6th and 8th weeks within the prefrontal cortex. The activity of complex II-III increased within the prefrontal cortex and hippocampus in each week of oral D-gal treatment. The activity of complex IV increased within the prefrontal cortex and hippocampus in the 1st, 2nd, 6th and 8th weeks of treatment. After 4 weeks of treatment the activity increased only in hippocampus. In conclusion, the present study showed that the oral administration of D-gal increased the activity of the mitochondrial respiratory chain complexes I, II, II-III and IV in the prefrontal cortex and hippocampus. Furthermore, the administration of D-gal via the oral route seems to cause the alterations in the mitochondrial respiratory complexes observed in brain neurodegeneration.

O presente estudo objetivou verificar a relação entre a organização da comunidade arbórea e variáveis ambientais em um fragmento de Floresta Ombrófila Mista. Para isso, na localidade da Coxilha Rica, no planalto sul catarinense, foram alocadas 50 parcelas de 200 m2 em um fragmento florestal, no qual foram amostrados, medidos (circunferência a altura peito, CAP) e identificados todos os indivíduos arbóreos vivos que apresentaram CAP igual ou superior a 15,7 cm. Em cada parcela, foram obtidas as variáveis ambientais: topografia, cobertura do dossel e características químicas e físicas dos solos. Foram calculados os estimadores fitossociológicos e ordenadas as parcelas em função da abundância das espécies, por meio da análise NMDS (Nonmetric multidimensional scalling). Em seguida, foi realizado ajuste entre a ordenação produzida e as variáveis ambientais, com as variáveis significativas (p ≤ 0,01) plotadas na forma de vetores. Foram amostrados 1.447 indivíduos, distribuídos em 69 espécies. Myrcia guianensis (Aubl.) DC. foi a espécie de maior valor de importância (VI=10,43%). Nas áreas com terreno mais declivoso, com maiores cotas altimétricas médias e com solos menos férteis, com maiores teores de MO, Al e Na, destacou-se a presença, entre outras espécies, de Drimys brasiliensis Miers. Nas áreas com o terreno mais plano e solos com maior fertilidade e menores teores de MO, Al e Na, foi comum Sebastiania commersoniana (Baill.) L.B. Sm. & Downs. Conclui-se que a topografia e as características químicas dos solos foram determinantes para a heterogeneidade florístico-estrutural no fragmento estudado.

The first autochthonous case of chikungunya virus (CHIKV) infection in Brazil was in September 2014 in the State of Amapá, and from there it rapidly spread across the country. The present study was conducted in 2016 in the state of Rio Grande do Norte, and the aims were to describe the epidemiological and the clinical aspects of the CHIKV outbreak. Biological samples from 284 chikungunya suspected cases were screened for CHIKV and Flavivirus (FV) RNA using qRT-PCR. Negative PCR samples were also screened for anti-CHIKV and anti-FVIgM by ELISA. CHIKV RNA were detected in 125 samples mostly occurring from January through March (46%), mainly affecting adults and older adults. We found a gradual decrease in viral RNA over the disease time. Anti-CHIKV IgM was found in 47.5% after negative CHIKV qRT-PCR. Interestingly, 45.0% simultaneously had positive results for CHIKV and FV IgM, suggesting the occurrence of virus co-circulation. The most frequent symptom was fever (91%). Women presented more chance to develop nausea and abdominal pain compared to men. Our data described and allows us to better understand the clinical and epidemiological aspects of the 2016 chikungunya outbreak in Rio Grande do Norte and can help in the early clinical diagnosis of the virus.

Parasitic diseases have attracted worldwide attention of their consequent impact on mortality and morbidity. Accordingly, several plants have been screened for antiparasitic activity aiming to create new alternatives for treatment. These diseases have been neglected and have not attracted worldwide attention (nowadays), the health concerns are focused in chronic diseases, but it is necessary to focus on parasitic diseases and look for prophylactic alternatives, such as plant extracts. Although camu-camu (Myrciaria dubia) seeds are a rich source of antioxidant antimutagenic, cytotoxic, anti-inflammatory, antimicrobial, antihypertensive and neuroprotective compounds, nothing is known about their antiparasitic effects. Thus, in the present study we aimed to evaluate five extracts of camu-camu seeds (100% water, 100% ethyl alcohol, 50% water + 50% ethyl alcohol, 25% water + 75% ethyl alcohol, and 75% water + 25% ethyl alcohol) in relation to their in vitro antimalarial, antischistosomicidal, leishmanicidal and anti-hemolytic effects. The extracts exhibited antischistosomicidal (ED50 values from 418.4 to >1000.0 µg/mL) and antimalarial activities (IC50 values from 24.2 to 240.8 µg/mL) for both W2 and 3D7 strains in all intra-erythrocytic stages. Correlation analysis showed that the toxic effects may mainly be attributed to methylvescalagin (r = −0.548 to −0.951, p

Objective The aim of this study was to investigate the cytotoxic effects of modified triple antibiotic paste and an experimental composition using calcium hydroxide on lipoteichoic acid (LTA)-primed apical papilla cells (APC). Material and Methods Human APC were tested for in vitro cytotoxicity of modified Triple Antibiotic Paste (mTAP – Ciprofloxacin, Metronidazole and Cefaclor at 1:1:1) and of a paste of Ciprofloxacin, Metronidazole and Calcium hydroxide (CMC – 1:1:2) and modified CMC (mCMC – 2:2:1) by using MTT assay. The substances were reconstituted in DMEM at 1,000 µg/mL and ¼ serially diluted before being kept in contact with cells for 1, 3, 5 and 7 days. Further, cells were primed with 1 µg/mL of Enterococcus faecalis LTA for 7 days prior to the viability test with 1,000 µg/mL of each substance. Statistical analysis was performed using one-way analysis of variance (ANOVA) and two-way ANOVA respectively followed by Tukey’s post-test. Significance levels were set at p

We investigated the effect in vitro and in vivo of doxycycline hyclate (Dx), a broad-spectrum antibiotic inhibitor of matrix metaloproteinases (MMPs), on adult Schistosoma mansoni worms and granulomatous liver inflammation in infected mice. Adult S. mansoni worms in culture treated with different concentrations of Dx (50–180 μg/mL) were studied for eight days to assess its morphology, eggs production, and mortality. Uninfected mice and those infected with S. mansoni, untreated and treated with praziquantel (Pz; 200 mg/kg) or Dx (50 mg/kg), were evaluated for 60 days. Our results indicated that Dx induced dose-dependent integumentary lesions (bubbles, tubercle collapse, spicule disappearance, peeling, and erosion), reduced mating rate and eggs-laying in adult S. mansoni worms. The effective lethal dose required to kill 50% of worms was 112.0 μg/mL Dx (DL50). In mice, S. mansoni infection induced hepatomegaly, intense IL-4, IL-10, TNF-α and TGF-β production, granulomatous inflammation and hepatic glycogen depletion. The number and size of the granulomas was similar in untreated and Dx-treated animals. Untreated animals showed a predominance of productive granulomas, and intense MMP-2 and MMP-9 activities. Dx-treated mice exhibited a significant increase in IL-4 levels, tissue inflammation, proportion of involutive granulomas, and hepatic collagenogenesis, as well as attenuated MMP-2 and MMP-9 activities. Our findings indicated that Dx is toxic to adult S. mansoni worms in vitro. However, in vitro beneficial effects were not reproduced in vivo, since Dx treatment increased liver granulomatous inflammation and collagenogenesis in S. mansoni-infected mice by a process potentially associated with Dx-mediated hepatic MMP-2 and MMP-9 inhibition.

Mushrooms are bioaccumulating organisms commonly used in selenium (Se) enrichment studies. However, the addition of Se in the culture medium may alter the distribution of other essential elements in the mushroom fruiting body. To evaluate the effects of the Se enrichment, Ca, Mg, and K distributions in pink oyster (Pleurotus djamor) and K and Mg distributions in white oyster (Pleurotus ostreatus) mushrooms were mapped by laser-induced breakdown spectroscopy (LIBS), which can be used at room temperature and requires minimal or no sample preparation. It was verified that Se enrichment favoured the accumulation of Ca in the lower part of the pink oyster mushroom and prevented the transport of this element to the edges and tops. The Se enrichment also altered the distribution of K and Mg, decreasing the numerical correlation between the K and Mg distributions (R² = 0.5871). In the white oyster mushroom, however, despite the changes in the morphological characteristics of the fruiting bodies after enrichment, there were generally nonsignificant differences in the K and Mg distributions between the control and the Se-enriched mushrooms.

Background: Knee osteoarthritis (OA) has been the main cause behind chronic pain and disabilities in the elderly population. The traditional treatment for knee OA pain currently concerns a number of combinations of pharmacological and nonpharmacological therapies. However, such combinations have displayed little effects on a significant group of subjects. In addition to this, pharmacological treatments often cause adverse effects, which limits their use on this population. Previous studies showed that chronic knee OA pain may be associated with maladaptive compensatory plasticity in pain-related neural central circuits indexed by a defective descending pain-inhibitory system. Transcranial direct current stimulation (tDCS) can revert some of these maladaptive changes, thus decreasing chronic pain sensation. Numerous studies have demonstrated that the use of anodal tDCS stimulation over the primary motor cortex (M1) has positive effects on chronic neuropathic pain. Yet, data on OA pain in elderly patients, including its effects on the endogenous pain-inhibitory system, remain limited. Objective: The objective of this study is to evaluate the efficacy of tDCS in reducing pain intensity caused by knee OA in elderly subjects with defective endogenous pain-inhibitory systems. Methods: We designed a randomized, sham-controlled, single-center, double-blinded clinical trial. Patients with knee OA who have maintained a chronic pain level during the previous 6 months and report a pain score of 4 or more on a 0-10 numeric rating scale (NRS) for pain in that period will undergo a conditioned pain modulation (CPM) task. Participants who present a reduced CPM response, defined as a decrease in NRS during the CPM task of less than 10%, and meet all of the inclusion criteria will be randomly assigned to receive 15 sessions of 2 mA active or sham tDCS for 20 minutes. A sample size of 94 subjects was calculated. The Brief Pain Inventory pain items will be used to assess pain intensity as our primary outcome. Secondary outcomes will include pain impact on functioning, mobility performance, quality of life, CPM, pressure pain threshold, touch-test sensory evaluation, and safety. Follow-up visits will be performed 2, 4, and 8 weeks following intervention. The data will be analyzed using the principle of intention-to-treat. Results: This study was approved by the institutional review board with the protocol number 1685/2016. The enrollment started in April 2018; at the time of publication of this protocol, 25 subjects have been enrolled. We estimate we will complete the enrollment process within 2 years. Conclusions: This clinical trial will provide relevant data to evaluate if anodal tDCS stimulation over M1 can decrease chronic knee OA pain in elderly subjects with defective CPM. In addition, this trial will advance the investigation of the role of central sensitization in knee OA and evaluate how tDCS stimulation may affect it. Trial Registration: ClinicalTrials.gov NCT03117231; https://clinicaltrials.gov/ct2/show/NCT03117231 (Archived by WebCite at http://webcitation.org/73WM1LCdJ) International Registered Report Identifier (IRRID): RR1-10.2196/11660

Innate immunity receptors (Toll-like receptors/TLRs and RIG-like receptors/RLRs) are important for the initial recognition of Zika virus (ZIKV), modulation of protective immune response, and IFN-α and IFN-β production. Immunological mechanisms involved in protection or pathology during ZIKV infection have not yet been determined. In this study, we evaluated the mRNA expression of innate immune receptors (TLR3, TLR7, TLR8, TLR9, melanoma differentiation-associated protein 5/MDA-5, and retinoic acid inducible gene/RIG-1), its adapter molecules (Myeloid Differentiation Primary Response Gene 88/Myd88, Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β/TRIF), and cytokines (IL-6, IL-12, TNF-α, IFN-α, IFN-β, and IFN-γ) in the acute phase of patients infected by ZIKV using real-time PCR in peripheral blood. Patients with acute ZIKV infection had high expression of TLR3, IFN-α, IFN-β, and IFN-γ when compared to healthy controls. In addition, there was a positive correlation between TLR3 expression compared to IFN-α and IFN-β. Moreover, viral load is positively correlated with TLR8, RIG-1, MDA-5, IFN-α, and IFN-β. On the other hand, patients infected by ZIKV showed reduced expression of RIG-1, TLR8, Myd88, and TNF-α molecules, which are also involved in antiviral immunity. Similar expressions of TLR7, TLR9, MDA-5, TRIF, IL-6, and IL-12 were observed between the group of patients infected with ZIKV and control subjects. Our results indicate that acute infection (up to 5 days after the onset of symptoms) by ZIKV in patients induces the high mRNA expression of TLR3 correlated to high expression of IFN-γ, IFN-α, and IFN-β, even though the high viral load is correlated to high expression of TLR8, RIG-1, MDA-5, IFN-α, and IFN-β in ZIKV patients.

Jaboticaba is a fruit from a native tree to Brazil,Plinia peruviana. Jaboticaba peels are an important source of antioxidant molecules such as phenolic compounds. This study aimed to evaluatein vitrothe activity of a hydroalcoholic extract of jaboticaba fruit peels (HEJFP) in wound healing processes and antioxidant activity in murine fibroblasts (L929 cell line). HEJFP concentrations (0.5, 1, 5, 10, 25, 50, 100, and 200 µg/mL) were tested in MTT assay and cell proliferation was verified at 100 µg/mL after 24 h and at 25, 50, and 100 µg/mL after 48 h of extract exposure. Evaluation of antioxidant activity was performed at 0.5, 5, 25, 50, and 100 µg/mL HEJFP concentrations. Cell treatment with HEJFP at 25, 50, and 100 µg/mL for 24 h followed by H2O2exposure for 3 h showed a strong cytoprotective effect.In vitroscratch wound healing assay indicated that none of tested HEJFP concentrations (0.5, 5, 25, 50, and 100 µg/mL) were capable of increasing migration rate after 12 h of incubation. These results demonstrate a positive effect of HEJFP on the wound healing process on L929 fibroblasts cell line, probably due to the antioxidant activity exhibited by phytochemicals in the extract.

The chemical composition of beans (Phaseolus vulgaris L.) provides several health benefits to humans. However, cooking beans before consumption is necessary to reduce the effect of certain toxic and anti-nutritional substances and to increase protein digestibility. However, heat treatment of beans may alter the chemical composition and nutrient bioaccessibility. In this study, the effect of cooking on elemental bioaccessibility in seven varieties of Phaseolus beans (common, black, fradinho, rajado, bolinha, jalo, and rosinha) were evaluated. In vitro gastrointestinal digestion of raw and cooked beans was performed to evaluate the bioaccessibility of calcium, copper, iron, sulfur, and zinc, combined with elemental determination using inductively coupled plasma optical emission spectrometry. The gastrointestinal digestion of raw and cooked grains showed that the cooking decreased the percentage of soluble iron in the fradinho (29%), rajado (27%), bolinha (20%), and rosinha (7%) varieties. The percentages of elemental bioaccessibility for raw or cooked black beans showed that sulfur (93%, raw and cooked) and copper (88% for raw and 89% for cooked) were the most bioaccessible essential elements; in contrast, calcium (41%) was the least accessible element in cooked grain.

Banana peels are well recognized as a source of important bioactive compounds, such as phenolics, carotenoids, biogenic amines, among others. As such, they have recently started to be used for industrial purposes. However, its composition seems to be strongly affected by biotic or abiotic ecological factors. Thus, this study aimed to investigate banana peels chemical composition, not only to get insights on eventual metabolic changes caused by the seasons, in southern Brazil, but also to identify the most relevant metabolites for these processes. To achieve this, a Nuclear magnetic resonance (NMR)-based metabolic profiling strategy was adopted, followed by chemometrics analysis, using the specmine package for the R environment, and metabolite identification. The results showed that the metabolomic approach adopted allowed identifying a series of primary and secondary metabolites in the aqueous extracts investigated. Besides, over the seasons the metabolic profiles of the banana peels showed to contain biologically active compounds relevant to the skin wound healing process, indicating the biotechnological potential of that raw material., To CNPq (National Counsel of Technological and Scientific Development) for financial support (Process n 407323/2013-9), to CAPES (Coordination for the Improvement of Higher Education Personnel), and EPAGRI (Agricultural Research and Rural Extension Company of Santa Catarina). The research fellowship from CNPq on behalf of M. Maraschin is acknowledged. The work is partially funded by Project PropMine, funded by the agreement between Portuguese FCT and Brazilian CNPq. This study was also partially supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte., info:eu-repo/semantics/publishedVersion

The purpose of this study was to assess, for the very first time, the effects of photodynamic therapy (PDT) on Schistosoma mansoni in vitro by measuring reactive oxygen species (ROS) generation throughout the treatment, as well as the behavior of the parasites (mating, motility and contraction/shortening), and damage to their tegument and excretory systems. The parasites were divided into 4 groups: control, photosensitizer, laser and PDT. Light irradiation was delivered with an InGaAlP low-level laser device operating at 660nm, with 40mW and 100J/cm2. For PDT, different toluidine blue dye (TBO) concentrations and times of exposure were utilized. Interestingly, TBO-mediated PDT was able to kill S. mansoni (P

Aedes spp. are considered the main vectors of dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses in the world. Arbovirus detection in Aedes mosquitoes can alert authorities to possible outbreaks, reducing the impact of these diseases. The purpose of this study was to perform an operational strategy for virological surveillance of DENV, ZIKV and CHIKV in adult Aedes aegypti and Aedes albopictus mosquitoes captured at different key-sites in an endemic urban area of the Northeast Region of Brazil, with the prospect of discussing its role as part of an alert system for outbreaks in critical areas. Residential and non-residential premises located in areas of recent of transmission of these arboviruses were selected for adult mosquito collection in the rainy season (July) of 2018. A total of 1068 adult mosquitoes were collected: 946 Culex quinquefasciatus (88.6%), 118 Ae. aegypti (11.0%), two Ae. albopictus (0.2%) and two Aedes taeniorhynchus (0.2%). Among the premises surveyed, recycling points (N = 48, 40.7%), municipal schools (N = 36, 30.5%) and junkyards (N = 31, 26.2%) were the places with the highest frequency of adult Ae. aegypti. Health units (including primary health care facilities and one hospital) (N = 23; 19.5%) together with residential premises (N = 11; 9.3%) presented the lowest frequencies. Total RNAs of the samples were extracted from Aedes mosquitoes and a nested reverse transcription (RT) polymerase chain reaction (PCR) assay for detecting and typing DENV, ZIKV and CHIKV was performed. From the 37 Aedes spp. pools analyzed (35 Ae. aegypti, one Ae. albopictus and one Ae. taeniorhynchus), seven were positive for DENV-3, including three pools containing Ae. aegypti females, one containing an Ae. aegypti engorged female and three comprised of Ae. aegypti males. The positive pools were composed of mosquitoes collected in public schools, health units, junkyards, recycling points and residential premises. Our findings reinforce the importance of continuous virological surveillance in Aedes mosquitoes, as a useful tool for detecting arboviruses circulation in vulnerable areas, even in low infestation seasons.

Beans (Phaseolus vulgaris L.) are among the main sources of protein and minerals. The cooking of the grains is imperative, due to reduction of the effect of some toxic and antinutritional substances, as well as increase of protein digestibility. In this study, the effects of cooking on albumins, globulins, prolamins, and glutelins concentration and determination of Fe associated with proteins for different beans varieties and on phaseolin concentration in common and black beans were evaluated. Different extractant solutions (water, NaCl, ethanol, and NaOH) were used for extracting albumins, globulins, prolamins, and glutelins, respectively. For the phaseolin separation NaOH, HCl, and NaCl were used. The total concentration of proteins was determined by Bradford method; Cu and Fe associated with phaseolin and other proteins were obtained by graphite furnace atomic absorption spectrometry and by flame atomic absorption spectrometry, respectively. Cooking promoted a negative effect on (1) the proteins concentrations (17 (glutelin) to 95 (albumin) %) of common beans and (2) phaseolin concentration (90%) for common and black beans. Fe associated with albumin, prolamin, and glutelin was not altered. In Fe and Cu associated with phaseolin there was an increase of 20 and 37% for the common and black varieties, respectively.

Iron (Fe) is an essential element for human nutrition, and its deficiency or low hemoglobin levels are a global health issue. Strategies aimed at increasing the amounts of essential elementals in agricultural products, as sprouts of adzuki bean (Vigna angularis), can be a way to minimize deficiencies, mainly in the populations of developing countries. Therefore, in this work was evaluated: production of Fe-enriched adzuki bean sprouts; Fe accumulation and translocation in plants in different culture media enriched with different Fe masses (500, 1000, 2000, and 3000 µg); and effects of the enrichment by means of 3000 µg FeIII-ethylenediaminetetraacetic acid (FeIII-EDTA): on the distribution of Ca, Cu, Fe, K, P, Mg, S, and Zn in different parts of the plant; on protein concentrations (albumins, globulins, prolamins, and glutelins) and their association with Fe in edible parts of the plant (stems); and on Fe bioaccessibility in the edible part of the plant (stems). The enrichment via FeIII-EDTA favored the translocation and increased Fe content of sprouts (75%), besides promoting interactions of Fe with albumins (141%), globulins (180%), and glutelins (93%). In the bioaccessibility assays, Fe was 83% bioaccessible in Fe-enriched sprouts.

Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of age-related dementia. Cognitive decline, beta-amyloid (Aβ) accumulation, neurofibrillary tangles, and neuroinflammation are the main pathophysiological characteristics of AD. Minocycline is a tetracycline derivative with anti-inflammatory properties that has a neuroprotective effect. The aim of this study was to evaluate the effect of minocycline on memory, neurotrophins and neuroinflammation in an animal model of AD induced by the administration of Aβ (1-42) oligomer. Male BALB/c mice were treated with minocycline (50 mg/kg) via the oral route for a total of 17 days, 24 h after intracerebroventricular administration of Aβ (1-42) oligomer. At the end of this period, was performed the radial maze test, and 24 h after the last minocycline administration, serum was collected and the cortex and hippocampus were dissected for biochemical analysis. The administration of minocycline reversed the memory impairment caused by Aβ (1-42). In the hippocampus, minocycline reversed the increases in the levels of interleukin (IL-1β), Tumor Necrosis Factor- alpha (TNF-α) and, IL-10 caused by Aβ (1-42). In the cortex, AD-like model increase the levels of IL-1β, TNF-α and, IL-4. Minocycline treatment reversed this. In the serum, Aβ (1-42) increased the levels of IL-1β and IL-4, and minocycline was able to reverse this action, but not to reverse the decrease of IL-10 levels. Minocycline also reversed the increase in the levels of Brain-derived neurotrophic factor (BDNF) in the hippocampus caused by Aβ (1-42), and reduced Nerve Growth Factor (NGF) increases in the total cortex. Therefore, our results indicate that minocycline causes improvements in the spatial memory, and cytokine levels were correlated with this effect in the brain it. Besides this, minocycline reduced BDNF and NGF levels, highlighting the promising effects of minocycline in treating AD-like dementia.

Made available in DSpace on 2018-11-27T19:49:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-09-01 Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) In this work, we present the in vitro schistosomicidal activity evaluation of the most active dichloromethane fraction (FDm) (ED50 = 83.5 mu g/mL) and of a mixture of the major alkaloids ((-)-cassine/(-)-spectaline, C/E) (ED50 = 37.4 mu g/mL) from the flowers of Senna spectabilis against adult worms and cercariae. We also demonstrate other toxic effects including paralysis of the adult worms, inhibition of the secretory activity, tegument lesions and cercaricidal activity. In the association test of Praziquantel (PZQ)-C/E, we observed up to 80% mortality of Schistosoma mansoni in comparison to PZQ monotherapy. Due to the diversity of the toxic effects, the schistosomicidal activity of C/E is likely a result of a multitarget mechanism involving the tegument, secretory system and neuromotor action. (C) 2016 Elsevier Ltd. All rights reserved. Univ Fed Alfenas Minas Gerais, BR-37130000 Alfenas, Brazil Univ Estadual Paulista Sao Paulo, BR-14800060 Araraquara, Brazil Univ Fed Uberlandia Minas Gerais, BR-38408100 Uberlandia, MG, Brazil Univ Estadual Paulista Sao Paulo, BR-14800060 Araraquara, Brazil

Plinia cauliflora (jaboticaba) is a native fruit tree from Brazilian rainforest widely used in popular medicine to prevent diarrhea, asthma, and infections. Studies have shown that the major therapeutic potential of jaboticaba fruits is on its peel, a rich source of anthocyanins. These secondary metabolites have well-known antioxidant and anti-inflammatory activities and have been claimed to be effective to treat diabetes, cancer, cardiovascular diseases, and stroke. This chapter describes a series of methodologies to evaluate important in vitro biological activities like cytotoxicity, proliferation, and migration of a hydroalcoholic extract of jaboticaba peel on mouse fibroblast L929 line. Assays to assess total phenolic, flavonoid, and anthocyanin contents and antioxidant activities are described as well.

In this study, the metabolomics characterization focusing on the carotenoid composition of ten cassava (Manihot esculenta) genotypes cultivated in southern Brazil by UV-visible scanning spectrophotometry and reverse phase-high performance liquid chromatography was performed. Cassava roots rich in -carotene are an important staple food for populations with risk of vitamin A deficiency. Cassava genotypes with high pro-vitamin A activity have been identified as a strategy to reduce the prevalence of deficiency of this vitamin. The data set was used for the construction of a descriptive model by chemometric analysis. The genotypes of yellow-fleshed roots were clustered by the higher concentrations of cis--carotene and lutein. Inversely, cream-fleshed roots genotypes were grouped precisely due to their lower concentrations of these pigments, as samples rich in lycopene (redfleshed) differed among the studied genotypes. The analytical approach (UV-Vis, HPLC, and chemometrics) used showed to be efficient for understanding the chemodiversity of cassava genotypes, allowing to classify them according to important features for human health and nutrition., FAPESC (Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina) and CNPq (Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico) for financial support. The research fellowship from CNPq on behalf of the last author is acknowledged. The work is partially funded by Project PropMine, funded by the agreement between Portuguese FCT and Brazilian CNPq. The authors also thank the FCT Strategic Project of UID/BIO/04469/2013 unit