Tolerability of glutamine supplementation in older adults: a double-blind placebo-controlled randomized clinical trial

In this double-blind placebo-controlled randomized investigation, we assessed the tolerability of glutamine in older adults recruited from three daycare centers. The relevance of studying glutamine supplementation in elderly patients lies in its potential to provide a well-tolerated intervention. Glutamine, a crucial amino acid, plays a vital role in various physiological processes, including immune function and protein synthesis. Understanding its impact on older adults is essential, given the potential implications for their health and well-being. Participants received a daily dose of 12.4 g of oral effervescent glutamine (EGln group) or maltodextrin (placebo group) for 60 days. Fifteen patients from each group completed the study. The mean ages were 77.0±9.1 and 79.0±6.9 years for the EGln and placebo groups, respectively. We evaluated body mass index, aminogram, hemogram, plasma levels of glucose, prealbumin, albumin, urea, creatinine, uric acid, C-reactive protein, vitamin D, calcium, sodium, potassium, and the plasma activities of aspartate aminotransferase and alanine aminotransferase. Notably, we quantified a broad array of inflammatory markers and growth factors providing a holistic understanding of the potential effects of glutamine supplementation. The results demonstrated that oral glutamine did not induce significant changes in any evaluated parameters, and no adverse effects were reported. This finding suggested that the dosage of glutamine used in this study was well-tolerated and safe. This information contributes to the broader understanding of glutamine supplementation, emphasizing its safety and supporting its potential as a viable intervention for maintaining health in aging individuals.

Adjuvant-induced arthritis promotes vascular hyporesponsiveness to phenylephrine through a nitric oxide-related mechanism

Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.

Diabetes, hemoglobin A1c, and cognitive performance in older adults: is there any impact of frailty? Evidence from the ELSI-Brazil study

Abstract The aim of this study was to evaluate the association between diabetes and cognitive performance in a nationally representative study in Brazil. We also aimed to investigate the interaction between frailty and diabetes on cognitive performance. A cross-sectional analysis of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) baseline data that included adults aged 50 years and older was conducted. Linear regression models were used to study the association between diabetes and cognitive performance. A total of 8,149 participants were included, and a subgroup analysis was performed in 1,768 with hemoglobin A1c data. Diabetes and hemoglobin A1c levels were not associated with cognitive performance. Interaction of hemoglobin A1c levels with frailty status was found on global cognitive z-score (P-value for interaction=0.038). These results suggested an association between higher hemoglobin A1c levels and lower cognitive performance only in non-frail participants. Additionally, undiagnosed diabetes with higher hemoglobin A1c levels was associated with both poor global cognitive (β=-0.36; 95%CI: -0.62; -0.10, P=0.008) and semantic verbal fluency performance (β=-0.47; 95%CI: -0.73; -0.21, P=0.001). In conclusion, higher hemoglobin A1c levels were associated with lower cognitive performance among non-frail participants. Higher hemoglobin A1c levels without a previous diagnosis of diabetes were also related to poor cognitive performance. Future longitudinal analyses of the ELSI-Brazil study will provide further information on the role of frailty in the association of diabetes and glycemic control with cognitive decline.

Pre-germination treatments of melon seeds for the production of seedlings irrigated with biosaline water

Abstract Melon production in the Brazilian semi-arid region is subject to the use of marginal waters with high salinity. However, the use of regulators and bioactivators in seed treatment can mitigate the harmful effects of salts in irrigation water. In this context, the objective was to evaluate the effect of pre-germination treatments with plant regulators and bioactivator in melon seeds for the production of seedlings irrigated with biosaline water from fish farming effluent. For this, two trials with the Goldex and Grand Prix hybrids were carried out separately. A completely randomized design was used in a 4 × 3 factorial scheme (pre-germination treatments × water dilutions). In addition to the control, the seeds were treated with salicylic and gibberellic acids and thiamethoxam. The waters used for irrigation were local-supply water, fish farming effluent (biosaline water) and these diluted to 50%. Physiological and biochemical analyses were performed for fourteen days. Biosaline water (5.0 dS m-1) did not affect the emergence of Goldex melon seedlings, but compromised the establishment of the Grand Prix cultivar. Seed pre-treatments with salicylic and gibberellic acids attenuate the effects of water salinity and promote growth modulations, resulting in more vigorous melon seedlings.

Resumo A produção de meloeiro no semiárido brasileiro está sujeita a utilização de águas marginais com salinidade elevada. Entretanto, a utilização de reguladores e bioativadores no tratamento de sementes podem mitigar os efeitos nocivos dos sais na água de irrigação. Nesse sentido, objetivou-se avaliar o efeito de tratamentos pré-germinativos com fitorreguladores e bioativador em sementes de melão para a produção de mudas irrigadas com água biossalina de efluente de piscicultura. Para isso, dois ensaios com os híbridos Goldex e Grand Prix foram realizados separadamente. Utilizou-se delineamento inteiramente casualizado em esquema fatorial 4 × 3 (tratamentos pré-germinativos × diluições de água). Além do controle, as sementes foram tratadas com os ácidos salicílico e giberélico, e tiametoxam. As águas utilizadas para irrigação foram a de abastecimento local, efluente de piscicultura (água biossalina) e estas diluídas a 50%. Durante quatorze dias foram realizadas as análises fisiológicas e bioquímicas. A água biossalina (5,0 dS m-1) não afetou a emergência de plântulas de meloeiro Goldex, mas prejudicou o estabelecimento da cultivar Grand Prix. Os pré-tratamentos de sementes com os ácidos salicílico e giberélico atenuam os efeitos da salinidade da água e promovem modulações no crescimento, proporcionando mudas de meloeiro mais vigorosas.

Pre-germination treatments of melon seeds for the production of seedlings irrigated with biosaline water / Tratamentos pré-germinativos de sementes de melão para a produção de mudas irrigadas com água biossalina

Abstract Melon production in the Brazilian semi-arid region is subject to the use of marginal waters with high salinity. However, the use of regulators and bioactivators in seed treatment can mitigate the harmful effects of salts in irrigation water. In this context, the objective was to evaluate the effect of pre-germination treatments with plant regulators and bioactivator in melon seeds for the production of seedlings irrigated with biosaline water from fish farming effluent. For this, two trials with the Goldex and Grand Prix hybrids were carried out separately. A completely randomized design was used in a 4 × 3 factorial scheme (pre-germination treatments × water dilutions). In addition to the control, the seeds were treated with salicylic and gibberellic acids and thiamethoxam. The waters used for irrigation were local-supply water, fish farming effluent (biosaline water) and these diluted to 50%. Physiological and biochemical analyses were performed for fourteen days. Biosaline water (5.0 dS m-1) did not affect the emergence of Goldex melon seedlings, but compromised the establishment of the Grand Prix cultivar. Seed pre-treatments with salicylic and gibberellic acids attenuate the effects of water salinity and promote growth modulations, resulting in more vigorous melon seedlings.

Resumo A produção de meloeiro no semiárido brasileiro está sujeita a utilização de águas marginais com salinidade elevada. Entretanto, a utilização de reguladores e bioativadores no tratamento de sementes podem mitigar os efeitos nocivos dos sais na água de irrigação. Nesse sentido, objetivou-se avaliar o efeito de tratamentos pré-germinativos com fitorreguladores e bioativador em sementes de melão para a produção de mudas irrigadas com água biossalina de efluente de piscicultura. Para isso, dois ensaios com os híbridos Goldex e Grand Prix foram realizados separadamente. Utilizou-se delineamento inteiramente casualizado em esquema fatorial 4 × 3 (tratamentos pré-germinativos × diluições de água). Além do controle, as sementes foram tratadas com os ácidos salicílico e giberélico, e tiametoxam. As águas utilizadas para irrigação foram a de abastecimento local, efluente de piscicultura (água biossalina) e estas diluídas a 50%. Durante quatorze dias foram realizadas as análises fisiológicas e bioquímicas. A água biossalina (5,0 dS m-1) não afetou a emergência de plântulas de meloeiro Goldex, mas prejudicou o estabelecimento da cultivar Grand Prix. Os pré-tratamentos de sementes com os ácidos salicílico e giberélico atenuam os efeitos da salinidade da água e promovem modulações no crescimento, proporcionando mudas de meloeiro mais vigorosas.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

The impact of diabetes and subclinical hypothyroidism association with coronary artery calcium: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: We aimed to analyze the association of diabetes and subclinical hypothyroidism with subclinical atherosclerosis measured by coronary artery calcium (CAC) in the baseline of the ELSA-Brasil study. Materials and methods: CAC was measured using a 64-detector computed tomographic scanner. The association of CAC > 0 was presented as an odds ratio (OR) and 95% confidence intervals (95%CI) in logistic models and as β (95%CI) in linear models after multivariable adjustment for confounders. Results: We analyzed 3,809 participants (mean-age (SD) 50.5 (8.8); 51.7% women). In the main analysis, we did not find an association of diabetes and subclinical hypothyroidism with CAC. However, in stratified analysis according to age strata, we found no significative interaction terms, an important heterogeneity between the groups, with the younger age strata showing an association of the group with both diseases and CAC > 0 (OR 7.16; 95%CI, 1.14; 44.89) with a wide but significative 95%CI, suggesting that the smaller number of participants in the younger group may influence the results. Our findings also showed an association of CAC > 0 and log (CAC+1) with diabetes in logistic (OR, 1.31; 95%CI, 1.05-1.63) and linear models (β, 0.24, 0.16, 0.40), respectively. Diabetes was independently associated with CAC > 0 in linear models. Discussion: In conclusion, our results showed a great heterogeneity in stratified analysis based on age in the younger age strata. Although we found no significant interaction factors, the smaller sample size for the analysis may influence the negative findings.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Attitudes and practices of travelers regarding COVID-19 vaccine and adverse reactions

Objective.In the context of the global COVID-19 pandemic, COVID-19 vaccines were made available to different countries. This study aimed to assess travelers' attitudes and practices toward the COVID vaccine and adverse events. Methods. A survey was conducted using a questionnaire from April 1 to June 30, 2021, among travelers who came for their COVID-19 test at the Institut Pasteur of Côte d'Ivoire.Results. A total of 527 travelers agreed to participate in this study, including 336 men and 161 women. Overall, 26% of respondents had already received their COVID-19 vaccine, while 76% of respondents responded they did not want to be vaccinated. The age of those most vaccinated (116) ranged from 25 to 64 years with a small proportion for those over 65 years (0.8%). Travelers (41) to France were the most vaccinated. All vaccinated persons (135) had a high level of education and were either Christian (89 persons), Muslim (45 persons) or animist (1 person). Adverse events related to the COVID vaccination were reported in seven individuals. These included muscle pain, fever and nausea. Conclusion.Negative attitudes towards vaccines are a major public health concern. In view of these results, for awareness raising, vaccination campaign may be focused on youthand people over 65 years of age. Public health messages containing information about vaccine safety should be tailored to address this vaccine hesitancy

Phylogenetic variants of Mycoplasma hominis from pregnant women and women presenting with infertility in Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria

Background: Much controversies have been associated with the pathogenicity of Mycoplasma hominis but little has been done to unravel the mystery behind the different views. This study aimed at investigating the genetic variants abounding within M. hominis and the distribution of the virulent genes among the variants. Methodology: Twenty (20) M. hominis isolates from high vaginal swabs of women (11 from pregnant women and 9 from women presenting with infertility) attending the Obstetrics and Gynaecology clinics of Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria, were sequenced using 16S rRNA universal gene target for the purpose of phylogenetic analysis and epidemiological typing. The isolates were also screened for the presence of M. hominis variable adherence antigen (vaa) and p120 virulent genes using primer constructs from the respective genes in a conventional PCR protocol. Results: Of the 20 M. hominis vaginal isolates, 4 phylogenetic strains were detected; strain MHS43 constituted 10/20 (50.0%) [2/9 (22.2%) from infertile women and 8/11 (72.7%) from pregnant women]; strain MHBS constituted 3/20 (15%) [3/9 (33.3%) from infertile women and 0/11 (0%) from pregnant women]; strain MHSWP2 constituted 4/20 (20.0%) [3/9 (33.3%) from infertile women and 1/11 (9.1%) from pregnant women]; while strain MHKC87 constituted 3/20 (15%) [1/9 (11.1%) from infertile women and 2/11 (18.2%) from pregnant women].Each of vaa and p120 genes was detected in 14 of 20 isolates, while 6 isolates did not carry the genes. A 2-way ANOVA test showed that none of the genes was significantly associated with a particular strain (p=0.8641). Conclusions: The different views regarding the pathogenicity of M. hominis may be linked to the heterogeneity within the species and lack of homogeneity in the virulent genes as witnessed both in the intra species and intra strain levels.

Total rupture of Achilles tendon induces inflammatory response and glial activation on the spinal cord of mice

Rupture of Achilles tendon is a common accident affecting professional and recreational athletes. Acute and chronic pain are symptoms commonly observed in patients with rupture. However, few studies have investigated whether Achilles tendon rupture is able to promote disorders in the central nervous system (CNS). Therefore, the current study aimed to evaluate nociceptive alterations and inflammatory response in the L5 lumbar segment of Balb/c mice spinal cord after Achilles tendon rupture. We found increased algesia in the paw of the ruptured group on the 7th and 14th days post-tenotomy compared with the control group. This phenomenon was accompanied by overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) as well as hyperactivation of astrocytes and microglia in nociceptive areas of L5 spinal cord as evidenced by intense GFAP and IBA-1 immunostaining, respectively. Biochemical studies also demonstrated increased levels of nitrite in the L5 spinal cord of tenotomized animals compared with the control group. Thus, we have demonstrated for the first time that total rupture of the Achilles tendon induced inflammatory response and nitrergic and glial activation in the CNS in the L5 spinal cord region.

Dark chocolate (70% cocoa) reduces craving in smokers with severe cardiovascular comorbidities without interference in anthropometric measures / Chocolate amargo (70% cacau) reduz fissura em tabagistas com comorbidades cardiovasculares graves sem interferir nas medidas antropométricas

ABSTRACT Objective: Analyze craving in smokers with cardiovascular comorbidities submitted to a nutritional approach. Methods: Two groups were randomized and submitted to clinical intervention (n = 32): Group 1 (G1, n = 15): ingested 40 g of chocolate containing 70% cocoa/day and behavioral intervention for smoking cessation for one month; Group 2 (G2, n = 17): control group, only behavioral intervention. Questionnaire of Smoking Urges-Brief (QSU-Brief) - Brazil version measured total craving and its factors. Anthropometric measurements verified the nutritional interference of the procedure and the serum assessment verified the interference of inflammatory processes related to smoking. The study was registered on the Brazilian Registry of Clinical Trials (ReBEC): RBR-83jr3. Results: After one month, compared to the initial evaluation, the G1 reduced the craving evaluated by the QSU-Brief and its Factors 1 and 2. Total QSU-Brief: 44.27 ± 15.82 x 27.00 ± 18.03 (p = 0.008); Factor 1: 21.90 ± 7.70 x 12.90 ± 8.87 (p = 0.006); Factor 2: 11.90 ± 6.30 x 7.00 ± 6.63 (0.007). G2 showed a reduction in total QSU-Brief and Factor 1, but not in Factor 2. QSU-Brief total 28.17 ± 17.24 x 19.52 ± 9.50 (p = 0.049); Factor 1: 14.47 ± 8.74 x 9.23 ± 6.11 (p = 0.046). Serum levels of cortisol, leptin, serotonin, C-Reactive Protein (CRP) and insulin did not show differences (p > 0.05). No anthropometric differences were found. Conclusion: The results demonstrate that daily consumption of chocolate for one month (70%) reduced craving in smokers at the beginning of treatment. Chocolate potentiated the well-known effect of behavioral counseling on Factor 1 (pleasurable drug effects) and also interfered with factor 2 (unpleasant withdrawal effects).

RESUMO Objetivo: Analisar o craving em fumantes com comorbidades cardiovasculares submetidos a uma abordagem nutricional. Métodos: Intervenção clínica (n = 32) com dois grupos randomizados: Grupo 1 (G1, n = 15): recebendo 40 g de chocolate contendo 70% de cacau/dia e intervenção comportamental para cessação do tabagismo por um mês; Grupo 2 (G2, n = 17): grupo controle, recebendo apenas intervenção comportamental pelo mesmo período. O Questionnaire of Smoking Urges-Brief (QSU-Brief) - versão Brasil foi utilizado para avaliar o craving. As medidas antropométricas verificaram a interferência nutricional do procedimento e a avaliação sérica, a interferência de processos inflamatórios relacionados ao tabagismo. O estudo foi registrado no Registro Brasileiro de Ensaios Clínicos (ReBEC), RBR-83jr3. Resultados: Um mês depois, comparado à avaliação inicial, o G1 reduziu o craving total e seus fatores (1 e 2). QSU-Brief total: 44,27 ± 15,82 x 27,00 ± 18,03 (p = 0,008); Fator 1: 21,90 ± 7,70 x 12,90 ± 8,87 (p = 0,006); Fator 2: 11,90 ± 6,30 x 7,00 ± 6,63 (0,007). G2: redução no QSU-Brief total e Fator 1, mas não no Fator 2. QSU-Brief total 28,17 ± 17,24 x 19,52 ± 9,50 (p = 0,049); Fator 1: 14,47 ± 8,74 x 9,23 ± 6,11 (p = 0,046). Níveis séricos de cortisol, leptina, serotonina, proteína C-reativa (PCR) e insulina não apresentaram diferenças (p > 0,05). Não foram encontradas diferenças antropométricas significativas. Conclusão: Os resultados demonstram que o consumo diário de chocolate por um mês (70%) reduziu o craving em fumantes no início do tratamento. O chocolate potencializou o conhecido efeito do aconselhamento comportamental sobre o Fator 1 (efeitos prazerosos da droga) e também interferiu no fator 2 (efeitos desagradáveis da abstinência).

Rivaroxabana em Pacientes Ambulatoriais com COVID-19 Leve ou Moderada: Fundamentação e Desenho do Estudo CARE (CARE - Coalition COVID-19 Brazil VIII) / Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE - Coalition COVID-19 Brazil VIII)

Resumo Fundamento Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. Objetivo Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. Métodos O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. Resultados Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. Conclusão O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Abstract Background Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting. Objective To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients. Methods The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests. Results Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Conclusion The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

Which are the best murine models to study Eosinophilic Chronic Rhinosinusitis? A contemporary review

Abstract Objective: Mechanisms that lead to Eosinophilic Chronic Rhinosinusitis (ECRS) are not fully established in the literature. It is desirable to assess ECRS in a model that embraces most of the related events. This article reviewed the murine models for ECRS and compared them regarding eosinophilic polypoid formation. Methods: The authors reviewed the articles that included the terms "chronic rhinosinusitis" OR "chronic sinusitis" AND "animal model". We analyzed articles in English that evaluated both the number of polyps and the number of eosinophils in the sinus mucosa of mouse models. Results: We identified a total of 15 articles describing different models of ECRS that used BALB/c or C57BL/6 mice, and different triggers/stimulants such as Staphylococcus aureus Enterotoxin B (SEB) + Ovalbumin (OVA); House Dust Mite (HDM) ± Ovalbumin (OVA); and Aspergillus oryzae Protease (AP) + Ovalbumin (OVA). OVA associated with SEB was the commonest protocol to induce ECRS in both BALB/c and C57BL/6 mice, and it produced a robust response of eosinophilic nasal polyps in both. AP + OVA protocol also led to a good ECRS response. The other models were not considered adequate to produce eosinophilic polyps in mice. Conclusion: In conclusion, OVA associated with SEB seems to produce the most robust eosinophilic sinonasal inflammation.

Neuromyelitis optica presenting as neurogenic bladder

Neuromyelitis optica(NMO) is an immune mediated disease of central nervous system primarily affecting optic nerves, spinal cord and brain stem. This case report describes a 24-year-old male with no comorbidities presented with high grade fever followed by proximal lower limbweakness and bilateral hydrouretero nephrosis without any lower urinary tract obstruction. He had clinical features of conus-cauda lesion with MRI spine showing features of longitudinally extensive transverse myelitis (LETM) and brain MRI showing involvement of splenium of corpus callosum. He improved with steroid therapy with in a period of 2 weeks and oral steroid was tapered of and stopped within a period of two months. There wasno relapse of symptoms so far.

Acquisition of endoscopic nasal surgery skills with a lamb's head model

Abstract Objectives: To evaluate the acquisition of surgical skills by otolaryngology residents and established the minimum number of dissections of a lamb's model to be performed before practicing on human patients. Methods: Nineteen second-year otolaryngology residents performed ten dissections each, five on each nasal cavity, always practicing the same three surgical procedures on the lamb model. Each student's training lasted 2-months, and the entire training intervention lasted 4-years, over four generations of residents. All dissections were recorded and were selected at random for examination by two independent otolaryngology surgeons, who were otherwise not involved in the research. Assessment of the 190 dissections used an instrument validated for surgical training of medical residents. Results: To a 1% significance level, statistical analysis revealed increased performance and satisfactory results were observed after the sixth dissection. Furthermore, after the eighth dissection, skill acquisition was relevant and sustained. Conclusion: Training in endoscopic nasal surgery on a lamb's head model improves surgical skills and handling of surgical instruments. Our results showed the relevance of the lamb model for training in otolaryngology surgery, impacting on patient safety. Level of evidence: 2.

Physico-chemical properties of calcium silicate-based sealers in powder/liquid and ready-to-use forms

Abstract Calcium silicate-based root canal sealers have been developed in powder/liquid or premixed ready-to-use forms. The evaluation of the physico-chemical properties of a prototype powder/liquid MTApex Sealer (Ultradent) in comparison to a ready-to-use material EndoSequence BC Sealer (Brasseler) was performed. The paste/paste epoxy resin-based AH Plus (Dentsply) served as control for comparisons. The sealers were evaluated (n = 6) regarding setting time (in dry and moist environments), flow and radiopacity, following the ISO-6876/2012 standard. Also, the pH was assessed. Material's surface and chemical characterization was evaluated using scanning-electron-microscopy (SEM) and energy-dispersive-spectrometry (EDS). Mixed ANOVA, Shapiro-Wilk, Levene, and post-hoc analysis with Bonferroni correction were performed at a significance level of 5%. MTApex Sealer exhibited the highest flow and EndoSequence BC Sealer had a significantly longer setting time in dry compared to the moist environment; however, for MTApex Sealer and AH Plus no significant changes occurred when additional moisture was provided. All materials exceeded 7 mm Al of radiopacity and showed a decreasing alkalinity over the 21 day-analysis. SEM/EDS evaluation resulted in peaks of calcium, silicon, and the respective radiopacifier. The prototype powder/liquid MTApex Sealer had the highest flow and similar setting time in both dry and moist environments; opposingly, EndoSequence BC Sealer was crucially influenced by external moisture. This suggests that the powder/liquid materials' setting seems to be more predictable.

Resumo Os cimentos endodônticos obturadores à base de silicato de cálcio foram desenvolvidos em formas pó/líquido ou pré-misturadas prontas para o uso. Foi realizada a avaliação das propriedades físico-químicas de um protótipo pó/líquido MTApex Sealer (Ultradent) em comparação com um material pronto para uso EndoSequence BC Sealer (Brasseler). O cimento obturador pasta/pasta à base de resina epóxi AH Plus (Dentsply) serviu de controle para as comparações. Os cimentos foram avaliados (n = 6) quanto a: tempo de presa (em ambientes secos e úmidos), escoamento e radiopacidade, seguindo a norma ISO-6876/2012; como também o pH. A superfície do material e a caracterização química foram realizadas utilizando a microscopia eletrônica de varredura (MEV) e espectrometria dispersiva de energia (EDS). ANOVA, Shapiro-Wilk, Levene e análise post-hoc com correção de Bonferroni foram realizadas com nível de significância de 5%. O MTApex Sealer exibiu um escoamento mais alto e o EndoSequence BC Sealer teve um tempo de presa significativamente mais longo em ambiente seco em comparação com o ambiente úmido; entretanto, para MTApex Sealer e AH Plus, nenhuma mudança significativa ocorreu quando umidade adicional foi fornecida. Todos os materiais excederam 7 mm de Al de radiopacidade e mostraram uma alcalinidade decrescente ao longo dos 21 dias de análise. A avaliação MEV/EDS resultou em picos de cálcio, silício e respectivo radiopacificador. O protótipo de pó/líquido MTApex Sealer teve o maior escoamento e tempo de presa semelhante em ambientes secos e úmidos; ao contrário, o EndoSequence BC Sealer foi influenciado de maneira crucial pela umidade externa. Isso sugere que a configuração dos materiais em pó/líquido parece ser mais previsível.

Validation of the Connecticut olfactory test (CCCRC) adapted to Brazil / Validação do teste de olfato de Connecticut (CCCRC) adaptado para o Brasil

Abstract Introduction Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. Objective To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. Methods In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. Results When evaluating the participants' performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p < 0.02, and individuals over 60 years of age showed worse performance (median: 6; 75th percentile: 6.5; 25th percentile). The test and retest of the 34 volunteers demonstrated that there was agreement (ICC, intraclass correlation coefficient) considered good in the left nostril (ICC = 0.65) and excellent in the right nostril (ICC = 0.77) in the combined score. Conclusion The CCCRC test adapted to Brazil showed normal values, similar to the originally-described test and validations in other countries, with a high reproducibility rate. Considering the highly favorable cost-benefit ratio, the adapted CCCRC is a very useful tool for measuring olfactory function in the Brazilian population.

Resumo Introdução Alterações olfativas são bastante comuns na população, causam significativo impacto na qualidade de vida. A documentação da função olfatória é fundamental para o diagnóstico, tratamento e seguimento de pacientes que cursam com doenças inflamatórias das vias aéreas superiores, neurodegenerativas ou infecções virais. Entre os diferentes testes de olfato existentes, o teste do Connecticut Chemosensory Clinical Research Center (CCCRC) é barato, de fácil aplicação, mas que ainda não foi avaliado em grande escala para a população brasileira. Objetivo Validar o teste de olfato CCCRC com adaptação para a população brasileira, avaliar o desempenho de voluntários saudáveis e a estabilidade do teste em retestes. Método Neste estudo fizemos adaptação cultural do teste CCCRC para o Brasil. Para validação e determinação dos escores de normalidade, aplicamos o teste em 334 voluntários saudáveis, com mais de 18 anos. O reteste foi ainda feito em até quatro semanas em 34 voluntários adicionais para avaliar concordância dos resultados. Resultados Avaliando o desempenho dos participantes, valores de normosmia e hiposmia leve foram obtidos em mais de 95% deles. Mulheres (58,4%) apresentaram melhor acurácia em relação aos homens (41,6%), p< 0,02; e indivíduos acima dos 60 anos apresentaram pior desempenho (mediana: 6; percentil 75: 6,5; percentil 25: 5). O teste e reteste dos 34 voluntários demonstrou que houve concordância (coeficiente de correlação intraclasse, CCI) considerada boa em narina esquerda (CCI = 0,65) e excelente em narina direita (CCI = 0,77) no escore combinado. Conclusão O teste CCCRC adaptado para o Brasil apresentou valores de normalidade semelhantes ao teste originalmente descrito e a validações em outros países, com alta taxa de reprodutibilidade. Considerando a relação custo-benefício altamente favorável, o CCCRC adaptado é uma ferramenta muito útil para mensuração da função olfatória na população brasileira.

Anti-diabetic and Lipidemic Effect of Muskmelon Fruits and Seeds on Streptozocin Induced Diabetic Rat

Background: The increasing prevalence of diabetes mellitus Worldwide and its complex nature of predisposing one to different ailments like obesity, eye defect, cardiovascular diseases etc. calls for alternative measures in the management of the disease. Muskmelon (Cucumis melo L.) is an underutilized food with a lot of nutritional and medical potential which are used traditionally in the management of different ailments like diabetes mellitus. Objective: The aim of this study was to evaluate the anti-diabetes and anti-lipidemic effects of muskmelon fruits and seeds in streptozotocin induced-diabetic rats. Methods: Diabetes was induced using intravenous Streptozotocin at a dose of 42 mg/kg of body weight into the tail veins to groups 2-5. Twenty-five male albino rats were divided into 5 groups, group 1 normal control, group 2- diabetic control, group 3- Glucophage treatment, group 4-500mg/kg BW muskmelon fruits extract, and group 5- 500mg/kg bw muskmelon seeds extract and were treated for 2 weeks. Fasting blood glucose, body weight, triglyceride, LDL, HDL and total cholesterol were evaluated. Results: The result shows that the extract caused a significant increase in the body weight, HDL-cholesterol, and a significant decrease in triglyceride, LDL-cholesterol, total cholesterol, and fasting blood glucose. Although the extract performed well there is a significant difference between the group that took Glucophage and the groups that ate muskmelon fruits and seed extract p<0.05 Conclusion: The result proved the anti-diabetic and anti-lipidemic effect of muskmelon fruits and seeds which could be added to the pool of other food used in the management of diabetes mellitus which will lead to diet diversification.

Effects of Psidium guajava L. Leaf Powder and Aloe vera L. Gel on Shelf Life of Citrus sinensis L. Fruits

Postharvest loss of fruits is a critical problem due of rapid deterioration during handling, transportation and warehousing. Edible coating over fruits is utilised to boost their quality and shelf life. The effects of leaf extracts of Psidium guajava and Aloe vera gel on the elongation of the shelf life of orange fruits were evaluated. Orange fruits were treated with Guava leaf powder and A. vera gel to assess their effectiveness in extending their shelf life and quality in storage. Weight loss, firmness, post-harvest decay, marketability and shelf life of uncoated and coated samples were evaluated all through the period of this study. Fungi were also isolated from deteriorating samples. A. vera was able to preserve the orange samples for 21 days; P. guajava preserved them for 17 days while the untreated fruit samples stayed for 14 days. Three fungi viz: Botryodiplodia theobromae, Fusarium oxysporum and Rhizopus stolonifer were isolated from the decomposing orange fruits. The result shows that orange fruits coated with A. vera gel and guava leaf powder is effective in extending the shelf-life of orange fruits when compared to untreated fruit (control) in the following order: A. vera>P. guajava > control. The findings from this study indicate that plant extracts could be employed to prolong the shelf life and improve quality of orange fruits.