A biogeographical appraisal of the threatened South East Africa Montane Archipelago ecoregion.

Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the 'South East Africa Montane Archipelago' (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates (amphibians, reptiles, birds, mammals) and 45 invertebrate species (butterflies, freshwater crabs), and two endemic genera of plants and reptiles. Existing dated phylogenies of endemic animal lineages suggests this endemism arose from divergence events coinciding with repeated isolation of these mountains from the pan-African forests, together with the mountains' great age and relative climatic stability. Since 2000, the SEAMA has lost 18% of its primary humid forest cover (up to 43% in some sites)-one of the highest deforestation rates in Africa. Urgently rectifying this situation, while addressing the resource needs of local communities, is a global priority for biodiversity conservation.

Early-Onset Dystonia and Visual Impairment Preceding Epileptic Encephalopathy Associated with PIGA Gene Mutation.

The association between dystonia and early-onset epileptic encephalopathy (EOEE) may have a genetic basis. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) germline mutations have been described in the last decade and associated with refractory EOEEs. Dysmorphisms and visceral abnormalities have also been reported. Here, we present the case of a now 8-month-old child who was evaluated for dystonia, visual impairment, and developmental delay at 2 months of age, followed by refractory focal seizures when he was 4 months old. The remaining examination was normal, besides an accelerated linear growth. His brain magnetic resonance and an extensive metabolic investigation failed to show any abnormalities. At 7 months of age, the exome sequencing found a hemizygous PIGA pathogenic variant-c.1352T > C (p.(Ile451Thr). Seizures improved after the association of carbamazepine with levetiracetam and the beginning of the ketogenic diet. To our knowledge, this is the first time the phenotype associated with this specific mutation is described. Our patient had the singularity of manifesting with remarkable dystonia, over 2 months before the onset of seizures. We also point to the utility of the gene sequencing approach in the diagnosis of patients with dystonia and EOEEs, since identification of the genetic cause may help in patient's management and families' empowerment.

Pregnancy Complications and Feto-Maternal Monitoring in Rabbits.

Rabbit production holds significant relevance in modern agriculture due to its potential as a sustainable source of high-quality protein and efficient feed conversion, contributing to food security and economic diversification. Nevertheless, studies incorporating feto-maternal monitoring in this species are uncommon. This review gathers research on the monitoring and evaluation of factors affecting rabbit gestation, providing a better understanding of the causes of prenatal development abnormalities. These include studies regarding how chronic maternal hypertension, gestational diabetes, maternal stress, ectopic gestation, maternal uterine ischemia and fetal hypoxia, intrauterine growth restriction, superfetation, maternal age, maternal nutritional status, maternal physical condition, maternal and embryonic genotype, and the intrauterine location of rabbit fetuses can potentially impact rabbits' reproduction and maternal and fetal health. Among other monitoring techniques, ultrasonography, considered one of the best tools for diagnosing pregnancy and conducting follow-up, is also reviewed. Details on measurable fetal-development parameters in rabbits and precautions to be considered before and during the examination are also provided. Additional studies are required to understand why some events occur and their consequences throughout gestation, allowing the determination of new biomarkers or cut-offs that can be helpful for early diagnosis and improve reproductive efficiency.

A site suitability analysis for castor (Ricinus communis L.) production during Brazil's second harvest incorporating disease prediction.

Castor (Ricinus communis L.) is an important industrial crop with a wide range of industrial and pharmaceutical applications. Brazil is among the largest castor-producing countries. Between 2004 and 2010, castor cultivation was stimulated with an emphasis towards biodiesel production. However, this was not enough to leverage the production of castor in Brazil, mainly due to the lack of structured trade and the competition with other cheaper raw materials for the production of biodiesel. Despite this failure, the species presents itself as an excellent alternative for crop rotation in the second crop among soybean, corn, beans, and cotton cultivation areas as the oil is highly valuable for other products. Moreover, it has drawn the attention of producers and researchers in Brazil for this potential rotation as it is considered a plant tolerant of water-deficiency and is highly susceptible to gray mold, a disease favored by high humidity in the final stages of the crop. For instance, its cultivation in the second crop in Cerrado regions, where rains occur in the early stages of the crop and cease when the plants reach the final stage of production, has been successful and shows great promise. The current study aimed to evaluate the suitability of environments throughout Brazil to grow castor, incorporating variables associated with the incidence of gray mold and confirm these findings based on existing castor trial data obtained from the literature. The site suitability analysis determined that 74.99 million hectares - 8.8% of Brazilian territory - are highly suitable for castor production during second harvest, mostly located in the Northeastern and Midwestern regions. These results are surprising since Brazil currently has around 7.8% (∼66.81 million hectares) of its territory occupied with agriculture (grains, fruits, vegetables, and perennial crops). The findings of this study provide a method to perform site suitability for crops using data associated with agronomic and disease characteristics, as is the case with gray mold that often results in significant losses in castor production. Also, this analysis provides evidence for the great potential of Brazil to increase castor production and meet the world demand for its oil through utilization of second-crop cultivation.

What We Know about Euterpe Genus and Neuroprotection: A Scoping Review.

The Euterpe genus (mainly Euterpe oleracea Martius, Euterpe precatoria Martius, and Euterpe edulis Martius) has recently gained commercial and scientific notoriety due to the high nutritional value of its fruits, which are rich in polyphenols (phenolic acids and anthocyanins) and have potent antioxidant activity. These characteristics have contributed to the increased number of neuropharmacological evaluations of the three species over the last 10 years, especially açaí of the species Euterpe oleracea Martius. The fruits of the three species exert neuroprotective effects through the modulation of inflammatory and oxidative pathways and other mechanisms, including the inhibition of the mTOR pathway and protection of the blood-brain barrier, all of them intimately involved in several neuropathologies. Thus, a better understanding of the neuropharmacological properties of these three species may open new paths for the development of therapeutic tools aimed at preventing and treating a variety of neurological conditions.

Gene variations related to the hepatocellular carcinoma: Results from a field synopsis and Bayesian revaluation.

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein-protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Trapeziectomy and Suture-Button Suspensionplasty for Basilar Thumb Arthritis: Is It Enough to Prevent First Ray Subsidence?

Introduction Trapeziectomy and suture-button suspensionplasty (SBS) are a novel option to treat end-stage trapeziometacarpal (TMC) osteoarthritis. Our purpose is to evaluate our outcomes with this technique and in this setting, with a minimum of 18 months of follow-up. Materials and Methods Twenty-eight patients were included, operated between 2016 and 2018. We recorded demographic data, preoperative Eaton stage, follow-up and operative times. The patients completed the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire and tip pinch, key pinch, and grip strength were measured. First metacarpal subsidence was calculated, and postoperative complications were documented. Results The average follow-up was 34 months. The mean QuickDASH was 32 at the final follow-up. The average strength results were 20 kg for grip, 3.6 kg for tip pinch, and 4.2 kg for key pinch. The rate of first ray subsidence was 10.7%. We encountered three complications: a hardware intolerance, a second metacarpal fracture, and a suture rupture. There was one reoperation to remove an implant. Conclusion Trapeziectomy and SBS functional results are similar to other techniques, with less subsidence of the first ray and allowing for early mobilization and fast recovery. This procedure is a safe and promising option in the treatment of TMC osteoarthritis, with good medium-term outcomes.

Glyphosate pollution of surface runoff, stream water, and drinking water resources in Southeast Brazil.

Glyphosate-based herbicides can be harmful to the environment and human health. Especially in developing countries, these herbicides are often used indiscriminately in agricultural and urban areas. Here, we optimized a simple and efficient flow injection-based spectrophotometric method to monitor environmentally relevant glyphosate concentrations in surface waters. The method was then used to assess the environmental mobility of glyphosate in Southeast Brazil by monitoring surface runoff from experimental agricultural soil plots that received glyphosate applications in 2015. Further, water samples from low-order streams were collected in five agricultural, urban, and natural areas, as well as from the 5th-order Rio das Mortes during the rainy season. Finally, 20 drinking water sources were sampled in urban, rural, and agricultural areas. Runoff from reference plots without glyphosate application showed concentrations below the method's detection limit of 0.49 mg.L-1, whereas runoff from plots with standard glyphosate application had concentrations between 1.24 and 6.1 mg.L-1. Similarly, concentrations in natural stream water were below the detection limit, whereas agricultural streams had concentrations of up to 3.7 mg.L-1 (average: 0.97 mg.L-1). In an agricultural stream monitored weekly, concentration peaks were observed after glyphosate applications by farmers, and concentrations were correlated to stream discharge. Urban streams had concentrations of up to 5.8 mg.L-1 (average: 2.6 mg.L-1), but samples from the catchment's major river were mostly below detection limits, illustrating the dilution of urban and agricultural runoff in high-order rivers. In the sampled drinking water resources, glyphosate pollution occurred mainly in the rainy season, with detectable concentrations between 0.5 and 8.7 mg.L-1 in 80% of the sampled drinking water sources. In conclusion, our results suggest considerable environmental mobility of glyphosate in the studied Southeast Brazilian catchment. Substantial pollution, well above national and international limits, was detected in surface runoff, stream water, and drinking water resources.

Qualidade de vida de acordo com o controle e gravidade da asma em pacientes pediátricos atendidos em um hospital em Belém do Pará / Quality of life according to asthma control and severity in pediatric patients at a hospital in Belém do Pará, north of Brazil

Introdução: A asma é uma doença inflamatória obstrutiva crônica que, mesmo com baixa letalidade, pode prejudicar a qualidade de vida das crianças e adolescentes. Estabelecer o quanto a gravidade da asma e o seu controle podem influenciar na qualidade de vida dos pacientes pode auxiliar em um melhor desfecho para os pacientes. Objetivo: Avaliar a qualidade de vida em crianças asmáticas de acordo com o controle de sintomas e a gravidade da doença. Métodos: Estudo transversal com inclusão de crianças asmáticas de 7 a 13 anos de idade acompanhadas no ambulatório de pneumologia pediátrica da Fundação Santa Casa de Misericórdia do Pará (FSCMPa). Dados sociodemográficos e clínicos foram obtidos por meio de uma ficha de identificação e do prontuário. O controle de sintomas foi avaliado pelo Teste de Controle da Asma e a gravidade foi determinada com base nos critérios do Global Initiative for Asthma. Para avaliação da qualidade de vida foi utilizado o Paediatric Asthma Quality of Life Questionnaire (PAQLQ). Resultados: Foram entrevistados 45 pacientes (57,7% meninos) com média de idade de 9,53±1,89 e mediana de 9 anos. Destes, 19, 11 e 15 foram classificados, respectivamente, com asma controlada (AC), asma parcialmente controlada (APC) e asma não controlada (ANC). Quanto à gravidade, 25, 19 e 1 foram classificados, respectivamente, com asma leve (AL), asma moderada (AM) e asma grave (AG). O grupo AC, quando comparado ao APC e ANC, apresentou maiores valores no escore geral do PAQLQ e em todos os domínios (p < 0,05). Quanto à adesão ao tratamento, verificou-se que pacientes com adesão terapêutica têm aproximadamente três vezes mais chance de ter prejuízo mínimo ou ausente na qualidade de vida do que pacientes não aderentes. Conclusão: Crianças asmáticas têm comprometimento da qualidade de vida relacionado ao inadequado controle dos sintomas e à não adesão terapêutica.

Background: Asthma is a chronic obstructive inflammatory disease that, even with low mortality, can impair the quality of life (QoL) of children and adolescents. Establishing to what extent asthma severity and control can influence patient QoL may contribute to better patient outcomes. Objective: To evaluate the QoL of children with asthma according to disease severity and symptom control. Methods: This was a cross-sectional study of asthmatic children aged 7 to 13 years followed up at the pediatric pulmonology outpatient clinic of Hospital Fundação Santa Casa de Misericórida do Pará (FSCMPa). Sociodemographic and clinical data were obtained using an identification form and from medical records. Symptom control was assessed by the Asthma Control Test, and severity was determined using the Global Initiative for Asthma criteria. The Pediatric Asthma Quality of Life Questionnaire (PAQLQ) was used to assess QoL. Results: We interviewed 45 patients (57.7% boys) with a mean age of 9.53 ± 1.89 years (median, 9 years). Of these, 19, 11, and 15 were classified as having well-controlled, partially controlled, and uncontrolled asthma, respectively. As for severity, 25, 19, and 1 were classified as having mild, moderate, and severe asthma, respectively. Children with well-controlled asthma had higher scores in total and in all domains of the PAQLQ than those with partially controlled or uncontrolled asthma (p<0.05). Regarding treatment adherence, patients with good adherence were approximately 3 times more likely to have minimal or no impairment in QoL than those with poor adherence. Conclusion: Asthmatic children have impaired QoL as a result of inadequate symptom control and non-adherence to treatment.

Analysis of adrenalectomy for the treatment of adrenal diseases performed by the Public Health Service in São Paulo between 2008 and 2019.

INTRODUCTION: treating benign (hormonally active or nonfunctional) and malignant adrenal cancer includes adrenalectomy. The expertise of surgeons and surgery performed by high-volume surgeons were associated with fewer complications and lower cost. We aimed to describe and compare the number of surgeries, mortality rate, and length of hospital stay for adrenalectomies performed between 2008 and 2019 in the public health system of São Paulo. METHODS: this was an ecological study. The data were collected using the TabNet Platform of the Unified Health System Department of Informatics. Outcomes analyzed included the number of surgeries performed, mortality rate during hospital stay, and length of hospital stay. Public hospitals in Sao Paulo were divided into three subgroups according to the surgical volume of adrenalectomies performed as well as hospitals with and without a residency program in Urology, and the results were compared among them. RESULTS: a total of 943 adrenalectomies were performed in Sao Paulo between 2008 and 2019. Mortality rates during hospital stay according to hospital surgical volume were no reported deaths in low-volume, 0.015% in intermediate-volume, and 0.004% in high-volume hospitals. The average length of the ICU stay was 1.03 days in low-volume, 2.8 in intermediate-volume, and 1.12 in high-volume hospitals (analysis between intermediate and high volume centers with statistical significance, p=0.016). CONCLUSIONS: despite no statistically significant differences among the groups analyzed, mortality rates were very low in all groups. ICU stay was shorter in high-volume centers than in intermediate-volume centers.

Polymorphisms in immune-mediator genes and the risk of dengue virus infection: Lights from a systematic revaluation by Bayesian approaches.

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.

Benign prostatic hyperplasia surgical treatment trends in the Public Health System in São Paulo, Brazil.

OBJECTIVE: To describe and compare the number of surgeries, mortality rate, length of hospital stay, and costs of transurethral resection of the prostate and open prostatectomy for the treatment of benign prostatic hyperplasia, between 2008 and 2018, in the Public Health System in São Paulo, Brazil. METHODS: Ecological and retrospective study using data from the informatics department of the Brazilian Public Health System database. Procedure codes were "open prostatectomy" and "transurethral resection of the prostate." The outcomes analyzed were compared between transurethral resection of the prostate and open prostatectomy according to the hospital surgical volume and presence or absence of a residency program. RESULTS: A total of 18,874 surgeries were analyzed (77% transurethral resection of the prostate) and overall mortality was not statistically different between procedures. Intermediate and high-volume centers had shorter length of hospital stay than low-volume centers for transurethral resection of the prostate (3.28, 3.02, and 6.58 days, respectively, p=0.01 and p=0.004). Length of hospital stay was also shorter for open prostatectomy in high-volume compared to low-volume centers (4.86 versus 10.76 days, p=0.036). Intrahospital mortality was inversely associated with surgical volume for transurethral resection of the prostate. Centers with residency program had shorter length of hospital stay considering open prostatectomy and less mortality regarding transurethral resection of the prostate. Open prostatectomy was 64% more expensive than transurethral resection of the prostate. CONCLUSION: The findings suggest the importance of investing in specialized centers, which could be potential referral centers for surgical cases.

Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19: Joint guideline of Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia, Sociedade Brasileira de Reumatologia. / Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19: Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia e Sociedade Brasileira de Reumatologia.

OBJECTIVE: Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. METHODS: A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. RESULTS: Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made. CONCLUSION: To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

OBJETIVOS: Há diversas terapias sendo utilizadas ou propostas para a COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é elaborar recomendações para subsidiar decisões sobre o tratamento farmacológico de pacientes hospitalizados com COVID-19 no Brasil. MÉTODOS: Um grupo de 27 membros, formado por especialistas, representantes do Ministério da Saúde e metodologistas, integra essa diretriz. Foi utilizado o método de elaboração de diretrizes rápidas, tomando por base a adoção e/ou a adaptação de recomendações a partir de diretrizes internacionais existentes (GRADE ADOLOPMENT), apoiadas pela plataforma e-COVID-19 RecMap. A qualidade das evidências e a elaboração das recomendações seguiram o método GRADE. RESULTADOS: Foram geradas 16 recomendações. Entre elas, estão recomendações fortes para o uso de corticosteroides em pacientes em uso de oxigênio suplementar, para o uso de anticoagulantes em doses de profilaxia para tromboembolismo e para não uso de antibacterianos nos pacientes sem suspeita de infecção bacteriana. Não foi possível fazer uma recomendação quanto à utilização do tocilizumabe em pacientes hospitalizados com COVID-19 em uso de oxigênio, pelas incertezas na disponibilidade e de acesso ao medicamento. Foi feita recomendação para não usar azitromicina, casirivimabe + imdevimabe, cloroquina, colchicina, hidroxicloroquina, ivermectina, lopinavir/ ritonavir, plasma convalescente e rendesivir. CONCLUSÃO: Até o momento, poucas terapias se provaram efetivas no tratamento do paciente hospitalizado com COVID-19, sendo recomendados apenas corticosteroides e profilaxia para tromboembolismo. Diversos medicamentos foram considerados ineficazes, devendo ser descartados, de forma a oferecer o melhor tratamento pelos princípios da medicina baseada em evidências e promover economia de recursos não eficazes.

Brazilian guidelines for the treatment of outpatients with suspected or confirmed COVID-19. A joint guideline of the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Medical Association (AMB), Brazilian Society of Angiology and Vascular Surgery (SBACV), Brazilian Society of Geriatrics and Gerontology (SBGG), Brazilian Society of Infectious Diseases (SBI), Brazilian Society of Family and Community Medicine (SBFMC), and Brazilian Thoracic Society (SBPT).

BACKGROUND: Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. METHODS: A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. RESULTS: Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. CONCLUSION: To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.

Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19: Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia e Sociedade Brasileira de Reumatologia / Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19: Joint guideline of Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia, Sociedade Brasileira de Reumatologia

Há diversas terapias sendo utilizadas ou propostas para a COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é elaborar recomendações para subsidiar decisões sobre o tratamento farmacológico de pacientes hospitalizados com COVID-19 no Brasil. Métodos: Um grupo de 27 membros, formado por especialistas, representantes do Ministério da Saúde e metodologistas, integra essa diretriz. Foi utilizado o método de elaboração de diretrizes rápidas, tomando por base a adoção e/ou a adaptação de recomendações a partir de diretrizes internacionais existentes (GRADE ADOLOPMENT), apoiadas pela plataforma e-COVID-19 RecMap. A qualidade das evidências e a elaboração das recomendações seguiram o método GRADE. Resultados: Foram geradas 16 recomendações. Entre elas, estão recomendações fortes para o uso de corticosteroides em pacientes em uso de oxigênio suplementar, para o uso de anticoagulantes em doses de profilaxia para tromboembolismo e para não uso de antibacterianos nos pacientes sem suspeita de infecção bacteriana. Não foi possível fazer uma recomendação quanto à utilização do tocilizumabe em pacientes hospitalizados com COVID-19 em uso de oxigênio, pelas incertezas na disponibilidade e de acesso ao medicamento. Foi feita recomendação para não usar azitromicina, casirivimabe + imdevimabe, cloroquina, colchicina, hidroxicloroquina, ivermectina, lopinavir/ ritonavir, plasma convalescente e rendesivir. Conclusão: Até o momento, poucas terapias se provaram efetivas no tratamento do paciente hospitalizado com COVID-19, sendo recomendados apenas corticosteroides e profilaxia para tromboembolismo. Diversos medicamentos foram considerados ineficazes, devendo ser descartados, de forma a oferecer o melhor tratamento pelos princípios da medicina baseada em evidências e promover economia de recursos não eficazes.

Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods: A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results: Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made. Conclusion: To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

Brazilian guidelines for the treatment of outpatients with suspected or confirmed COVID-19. A joint guideline of the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Medical Association (AMB), Brazilian Society of Angiology and Vascular Surgery (SBACV), Brazilian Society of Geriatrics and Gerontology (SBGG), Brazilian Society of Infectious Diseases (SBI), Brazilian Society of Family and Community Medicine (SBFMC), and Brazilian Thoracic Society (SBPT)

ABSTRACT Background Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. Methods A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. Results Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. Conclusion To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.

Living in the Southern Hemisphere: Metabolic Syndrome and Its Components in Amazonian Riverine Populations.

The metabolic syndrome (MetS) epidemic is a global challenge. Although developing countries (including Brazil, India, and South Africa) present a higher proportion of deaths by cardiovascular diseases than developed countries, most of our knowledge is from these developed countries. Amazonian riverine populations (ARP), as well as other vulnerable populations of the Southern Hemisphere, share low-income and traditional practices, among other features. This large cross-sectional study of ARP (n = 818) shows high prevalence of hypertension (51%) and obesity (23%). MetS was diagnosed in 38% of participants (especially in women and 60-69 years-old individuals) without the influence of ancestry. Only 7-8% of adults had no cardio-metabolic abnormalities related to MetS. Atherogenic dyslipidemia (low HDL-cholesterol) was generally observed, including in individuals without MetS. Still, slight differences were detected between settings with a clear predominance of hypertension in Tucuruí. Hypotheses on possible genetic influence and factors (nutrition transition and environmental pollutants -mercury) are proposed for future studies. Moreover, a roadmap to MetS progression based on the most prevalent components is provided for the development of tailored interventions in the Amazon (initially, individuals would present low HDL-cholesterol levels, later progressing to increased blood pressure characterizing hypertension, and ultimately reaching MetS with obesity). Our alarming results support the need to improve our knowledge on these vulnerable populations.

A rare sporadic pancreatic desmoid fibromatosis with splenic vein invasion diagnosed by CT scan-guided core needle biopsy: a case report with possible differential diagnosis from metastatic colorectal or renal cancer.

Desmoid tumor is a rare fibroblastic proliferation with a variable and often unpredictable clinical course that arises in the deep soft tissues and is characterized by infiltrative growth with tendency to local recurrence but not to metastasize. A 49-year-old man was referred for a second opinion regarding a pancreatic mass. With a personal neoplastic background of two different tumors, we considered as a high probability of being metastatic of his previous colorectal or renal cancers, in a peritoneal implant. Due to the unclear origin and nature of the mass, we opted for requesting a computed tomography (CT)-guided core needle biopsy that could eventually lead to a surgical and/or chemotherapy treatment. So far, this is the first case of pancreatic desmoid fibromatosis with splenic vein invasion diagnosed by CT scan-guided core needle biopsy. Surgery should be performed by an experienced surgeon as first-line therapy, provided expected surgical morbidity is limited.

A genetic interaction of NRXN2 with GABRE, SYT1 and CASK in migraine patients: a case-control study.

BACKGROUND: Migraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles. Our aim was to continue exploring the role and interaction of proteins involved in the control and promotion of neurotransmission in migraine susceptibility. METHODS: A case-control study was performed comprising 183 migraineurs (148 females and 35 males) and 265 migraine-free controls (202 females and 63 males). Tagging single nucleotide polymorphisms of NRXN2 were genotyped to assess the association between NRXN2 and migraine susceptibility. The χ2 test was used to compare allele frequencies in cases and controls and odds ratios were estimated with 95% confidence intervals. Haplotype frequencies were compared between groups. Gene-gene interactions were analysed using the Multifactor Dimensionality Reduction v2.0. RESULTS: We found a statistically significant interaction model (p = 0.009) in the female group between the genotypes CG of rs477138 (NRXN2) and CT of rs1158605 (GABRE). This interaction was validated by logistic regression, showing a significant risk effect [OR = 4.78 (95%CI: 1.76-12.97)] after a Bonferroni correction. Our data also supports a statistically significant interaction model (p = 0.011) in the female group between the GG of rs477138 in NRXN2 and, the rs2244325's GG genotype and rs2998250's CC genotype of CASK. This interaction was also validated by logistic regression, with a protective effect [OR = 0.08 (95%CI: 0.01-0.75)]. A weak interaction model was found between NRXN2-SYT1. We have not found any statistically significant allelic or haplotypic associations between NRXN2 and migraine susceptibility. CONCLUSIONS: This study unravels, for the first time, the gene-gene interactions between NRXN2, GABRE - a GABAA-receptor - and CASK, importantly it shows the synergetic effect between those genes and its relation with migraine susceptibility. These gene interactions, which may be a part of a larger network, can potentially help us in better understanding migraine aetiology and in development of new therapeutic approaches.