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205. Serum folate levels and cognitive performance in the ELSA-Brasil baseline assessment

Author

Itamar de Souza SANTOS, Claudia Kimie SUEMOTO, José Benedito Ramos VALLADÃO-JUNIOR, Simin LIU, Sandhi Maria BARRETO, Ligia Maria Giongo FEDELI, Paulo Andrade LOTUFO, and Isabela Martins BENSENOR

Subjects
Cognition, Dietary Supplements, Epidemiology, Folic Acid, Memory, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

ABSTRACT Background: Most studies that analyze the association between serum folate levels and cognitive function either restrict their assessments to specific clinical scenarios or do not include middle-aged individuals, to whom strategies for preventing cognitive impairment may be more feasible. Objective: To examine the association between serum folate levels and cognitive function in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment. Methods: Data from 4,571 ELSA-Brasil participants who live in the state of São Paulo, aged 35-74 years, were analyzed. The word list learning, delayed recall, word recognition, verbal fluency, and Trail Making Test Part B consisted in the cognitive tests. For each test, age, sex, and education-specific standardized scores and a global cognitive score were calculated. Crude and adjusted linear regression models were used to examine the associations of serum folate levels with cognitive test scores. Results: In multivariable-adjusted models, serum folate was not associated with global cognitive score (β=-0.043; 95% confidence interval [95%CI] -0.135 to 0.050 for lowest vs. highest quintile group), nor with any cognitive test performance. We did not find associations between serum folate and global cognitive scores in subgroups stratified by age, sex, or use of vitamin supplements either. Conclusions: We did not find significant associations between serum folate and cognitive performance in this large sample, which is characterized by a context of food fortification policies and a consequent low frequency of folate deficiency. Positive results from previous studies may not apply to the increasingly common contexts in which food fortification is implemented, or to younger individuals.

Published
2020
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206. Galenia africana plant extract exhibits cytotoxicity in breast cancer cells by inducing multiple programmed cell death pathways

Author

Luqmaan Mohamed, Suparna Chakraborty, K.N. ArulJothi, Lawrence Mabasa, Kenza Sayah, Leticia V. Costa-Lotufo, Anwar Jardine, and Sharon Prince

Subjects
Galenia africana (Kraalbos), Breast cancer, Cytotoxicity, Autophagy, Apoptosis, Necroptosis, Therapeutics. Pharmacology, RM1-950
Abstract

Globally, breast cancer is the most common malignancy in women and the second most common cause of cancer-related death among women. There is therefore a need to identify more efficacious therapies for this neoplasm. Galenia africana (Kraalbos) is a perennial shrub found in Southern Africa and is used by the indigenous people to treat various ailments. There has therefore been much interest to establish the scientific basis for the medicinal properties of Kraalbos. This study aimed to investigate and characterise the anti-cancer activity of an ethanolic extract of Kraalbos leaves, KB2, against oestrogen receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. LC-MS/MS analyses identified the phytochemicals 7′-hydroxyflavanone, 5′,7'-dihydroxyflavanone, 2′,4′-dihydroxydihydrochalcone and 2′,4′-dihydroxychalcone in KB2. KB2 exhibited an IC50 of 114 µg/ml and 130.5 µg/ml in MCF-7 and MDA-MB-231 cells respectively, selectively inhibited their long-term survival and reduced their migration which correlated with a decrease in EMT markers. It induced oxidative stress (ROS), DNA damage (increased levels of γ-H2AX), and triggered cell cycle arrests in MCF-7 and MDA-MB-231 cells. Importantly, KB2 activated intrinsic (cleaved caspase 9) and extrinsic (cleaved caspase 8) apoptosis, necroptosis (p-RIP3 and the downstream target of the necrosome, pMLKL) and autophagy (LC3II). Co-treatment of the breast cancer cells with KB2 and the autophagy inhibitor bafilomycin A1 resulted in a significant increase in cell viability which suggests that KB2 induced autophagy is a cell death mechanism.

Published
2020
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207. Longitudinal measurement invariance of neuropsychological tests in a diverse sample from the ELSA-Brasil study

Author

Laiss Bertola, Isabela M. Benseñor, Alden L. Gross, Paulo Caramelli, Sandhi Maria Barreto, Arlinda B. Moreno, Rosane H. Griep, Maria Carmen Viana, Paulo A. Lotufo, and Claudia K. Suemoto

Subjects
Parallel tests, longitudinal change, cognition, low and middle income countries, memory, executive function, Psychiatry, RC435-571
Abstract

Objective: Longitudinal measurement invariance analyses are an important way to assess a test’s ability to estimate the underlying construct over time, ensuring that cognitive scores across visits represent a similar underlying construct, and that changes in test performance are attributable to individual change in cognitive abilities. We aimed to evaluate longitudinal measurement invariance in a large, social and culturally diverse sample over time. Methods: A total of 5,949 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were included, whose cognition was reassessed after four years. Longitudinal measurement invariance analysis was performed by comparing a nested series of multiple-group confirmatory factor analysis models (for memory and executive function factors). Results: Configural, metric, scalar and strict invariance were tested and supported over time. Conclusion: Cognitive temporal changes in this sample are more likely to be due to normal and/or pathological aging. Testing longitudinal measurement invariance is essential for diverse samples at high risk of dementia, such as in low- and middle-income countries.

Published
2020
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208. A Prevalência da Hipotensão Ortostática e a Distribuição da Variação Pressórica no Estudo Longitudinal da Saúde do Adulto

Author

Ana Paula Costa Velten, Isabela Bensenor, Paulo Lotufo, and José Geraldo Mill

Subjects
Hipotensão Ortostática/epidemiologia, Prevalência, Doença da Artéria Coronariana, Pressão Arterial, Posição Ortostática, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Resumo Fundamento A hipotensão ortostática (HO) tem sido negligenciada na clínica não havendo estudos sobre sua prevalência na população brasileira. Objetivo Determinar a prevalência de HO e a variação da pressão arterial (PA) após manobra postural no Estudo Longitudinal da Saúde do Adulto. Métodos No presente estudo descritivo da linha de base (N = 14.833 indivíduos, 35-74 anos), os participantes ficavam deitados por 20 minutos e então levantavam ativamente, com a medida da PA em supino e aos 2, 3, e 5 minutos de ortostase. A HO foi definida por queda ≥ 20 mmHg na PA sistólica e/ou queda ≥ 10 mmHg na PA diastólica aos 3 minutos, sendo determinada a sua prevalência com intervalo de confiança de 95% (IC95%). A distribuição da variação da PA após a manobra postural foi determinada numa subamostra (N = 8.011) após remoção de participantes com morbidade cardiovascular e/ou diabetes. Resultados A prevalência de HO foi de 2,0% (IC95%: 1,8 – 2,3), crescente com a idade. Se o critério for a mesma queda pressórica em qualquer das medidas, a prevalência aumenta para 4,3% (IC95%: 4,0 – 4,7). Em presença de HO houve relato de sintomas (tontura, escotomas, náuseas, etc.) em 19,7% dos participantes (IC95%: 15,6 – 24,6) e em apenas 1,4% (IC95%: 1,2 – 1,6) dos sem HO. Os escores-Z −2 das variações da PA antes e após manobra postural na subamostra foram de −14,1 mmHg na PA sistólica e −5,4 mmHg na diastólica. Conclusão A prevalência de HO varia em função do momento da aferição da PA. Os pontos de corte atuais podem subestimar a ocorrência de HO na população. (Arq Bras Cardiol. 2020; 114(6):1040-1048)

Published
2020
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209. Níveis Elevados de Netrina-1 e IL-1β em Mulheres Idosas com SCA: Pior Prognóstico no Acompanhamento de Dois Anos

Author

Paola Leocádio, Penélope Menta, Melissa Dias, Júlia Fraga, Alessandra Goulart, Itamar Santos, Paulo Lotufo, Isabela Bensenor, and Jacqueline Alvarez-Leite

Subjects
Síndrome Coronariana Aguda/fisiopatologia, Nitrina-1, Interleucina- 1 beta, Remodelamento Atrial, Hipertensão, Diabetes Mellitus, Dislipidemias, Acidente Vascular Cerebral, Idoso, Mulheres, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Resumo Fundamento Vários marcadores têm sido avaliados quanto a um potencial impacto nas decisões clínicas ou na predição de mortalidade na síndrome coronariana aguda (SCA), incluindo Netrina-1 e IL-1β. Objetivo Examinamos o valor prognóstico de Netrina-1 e IL-1β em pacientes com SCA (2 anos de acompanhamento). Métodos Avaliamos Netrina-1, IL-1β e outros fatores de risco em amostras de soro de 803 pacientes. Curvas de Kaplan-Meier e regressão de Cox foram usadas para análise de óbito por todas as causas, óbito por doenças cardiovasculares (DCV) e desfecho combinado de infarto agudo do miocárdio (IAM) fatal ou novo IAM não fatal, considerando p < 0,05. Resultados Houve 115 óbitos por todas as causas, 78 óbitos por DCV e 67 eventos no desfecho combinado. Níveis de Netrina-1 acima da mediana (> 44,8 pg/mL) foram associados a pior prognóstico (óbito por todas as causas e por DCV) em mulheres idosas, mesmo após o ajuste do modelo (HR: 2,08, p = 0,038 e HR: 2,68, p = 0,036). Níveis de IL-1β acima da mediana (> 13,4 pg/mL) em mulheres idosas foram associados a risco aumentado para todos os desfechos após o ajuste (todas as causas - HR: 2,03, p = 0,031; DCV - HR: 3,01, p = 0,013; desfecho combinado - HR: 3,05, p = 0,029). Para homens, não foram observadas associações entre Netrina-1 ou IL-1β e os desfechos. Conclusão Níveis séricos elevados de Netrina-1 e IL-1β mostraram associação significativa com pior prognóstico em idosas do sexo feminino. Eles podem ser úteis como indicadores prognósticos em SCA. (Arq Bras Cardiol. 2020; 114(3):507-514)

Published
2020
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210. Amount of physical activity necessary for a normal level of high-sensitivity C-reactive protein in ELSA-Brasil: a cross-sectional study

Author

Ciro Oliveira Queiroz, Francisco Pitanga, Paulo Andrade Lotufo, Maria Del Carmen Bisi Molina, Estela Maria Leão de Aquino, and Maria Conceição Chagas Almeida

Subjects
Motor activity, Risk factors, ROC curve, Cardiovascular diseases, Inflammation, Exercises, Chronic diseases, ELSA-Brasil, Medicine
Abstract

ABSTRACT BACKGROUND: Studies have shown that physical activity levels can be inversely associated with high-sensitivity C-reactive protein (hs-CRP) levels. However, the amount of physical activity required to maintain normal hs-CRP levels is still a matter for speculation. OBJECTIVE: To identify the amount of physical activity necessary to discriminate the hs-CRP levels in adults. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: The study sample comprised 10,231 adults aged 35 to 74 years who were participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Receiver operating characteristic (ROC) curves were constructed to compare the amount of physical activity in two domains (leisure time and commuting) with hs-CRP levels. The sensitivity and specificity were calculated to identify the best cutoff for physical activity level that would be needed to maintain normal levels of hs-CRP (< 3 mg/l). RESULTS: The area under the ROC curve was only statistically significant for discriminating normal levels of hs-CRP according to the amount of physical activity when the two study domains were added together. The accumulated physical activity level of 200 minutes/week was the best cutoff for discriminating normal levels of hs-CRP in adults of both sex. CONCLUSIONS: Physical activity in the leisure-time and commuting domains together, of duration 200 minutes/week, was associated with normal hs-CRP values.

Published
2020
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211. Chemical composition of the Brazilian native Cinnamomum stenophyllum (Meisn.) Vattimo-Gil essential oil by GC-qMS and GC × GC-TOFMS, and its cytotoxic activity

Author

Fabiana L. Silva, Raquel V.S. Silva, Paola C. Branco, Letícia V. Costa-Lotufo, Cynthia Murakami, Maria C.M. Young, Débora A. Azevedo, and Paulo R.H. Moreno

Subjects
Chemistry, QD1-999
Abstract

Cinnamomum stenophyllum (Meisn.) Vattimo-Gil (Lauraceae) is a native and vulnerable Brazilian species restricted to the Atlantic Forest. The leaf essential oil obtained by hydrodistillation was characterized for the first time by two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC-TOFMS). This analysis resulted in the tentatively identification of 80 compounds, showing the superior performance of this method in comparison to the seven compounds identified by GC–MS. The identified compounds included 8 ketones, 7 monoterpene hydrocarbons, 30 oxygenated monoterpenes, 4 sesquiterpene hydrocarbons and 23 oxygenated sesquiterpenes, showing that the C. stenophyllum oil contained mostly oxygenated mono and sesquiterpenes. The oil cytotoxicity was tested against two human cancer cell lines, colon adenocarcinoma (HCT-116) and breast cancer carcinoma (MCF-7), and the non-tumor retinal pigment epithelial cells (RPE) using the colorimetric MTT assay. Both cancer cell lines were sensible to leaf essential oil, with IC50 50 μg/mL), suggesting selectivity to cancer cells. The results showed that the C. stenophyllum leaf essential oil has a cytotoxic potential, presenting several compounds already known as biologically active against tumor cells. Keywords: Cinnamomum stenophyllum, Essential oil, GC×GC-TOFMS, Oxygenated mono- and sesquiterpenes, Cytotoxic activity

Published
2020
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212. Precision non-implantable neuromodulation therapies: a perspective for the depressed brain

Author

Lucas Borrione, Helena Bellini, Lais Boralli Razza, Ana G. Avila, Chris Baeken, Anna-Katharine Brem, Geraldo Busatto, Andre F. Carvalho, Adam Chekroud, Zafiris J. Daskalakis, Zhi-De Deng, Jonathan Downar, Wagner Gattaz, Colleen Loo, Paulo A. Lotufo, Maria da Graça M. Martin, Shawn M. McClintock, Jacinta O’Shea, Frank Padberg, Ives C. Passos, Giovanni A. Salum, Marie-Anne Vanderhasselt, Renerio Fraguas, Isabela Benseñor, Leandro Valiengo, and Andre R. Brunoni

Subjects
Major depressive disorder, transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, precision medicine, Psychiatry, RC435-571
Abstract

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more “precision-oriented” practice.

Published
2020
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213. Molecular evidences confirm the taxonomic separation of two sympatric congeneric species (Mollusca, Gastropoda, Neritidae, Neritina)

Author

Cristiane Xerez Barroso, João Eduardo Pereira de Freitas, Helena Matthews-Cascon, Luis Ernesto Arruda Bezerra, and Tito Monteiro da Cruz Lotufo

Subjects
Zoology, QL1-991
Abstract

A reliable taxonomy, together with more accurate knowledge of the geographical distribution of species, is a fundamental element for the study of biodiversity. Multiple studies on the gastropod family Neritidae record three species of the genus Neritina in the Brazilian Province: Neritina zebra (Bruguière, 1792), Neritina virginea (Linnaeus, 1758), and Neritina meleagris Lamarck, 1822. While N. zebra has a well-established taxonomic status and geographical distribution, the same cannot be said regarding its congeners. A widely cited reference for the group in Brazil considers N. meleagris a junior synonym of N. virginea. Using a molecular approach (phylogenetic, species delimitation, and statistical parsimony network analyses), based on two mitochondrial markers (COI and 16S), this study investigated if N. virginea and N. meleagris are distinct species. The molecular results confirmed the existence of two strongly supported distinct taxonomic entities in the Brazilian Province, which is consistent with the morphological descriptions previously proposed for N. virginea and N. meleagris. These species occur in sympatry in the intertidal sandstone formations of Northeastern Brazil. Despite the great variation in the colour patterns of the shells, the present study reinforced previous observations that allowed the differentiation of these two species based on these patterns. It also emphasized the importance of the separation of these two clades in future studies, especially those conducted in the Brazilian Province, since these species may cohabit.

Published
2020
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214. Relationships between worry and depressive symptoms during two group therapies for generalized anxiety disorder

Author

Daniel Santos Martins, Thiago Pacheco de Almeida Sampaio, and Francisco Lotufo Neto

Subjects
Anxiety, anxiety disorders, worry, depression, psychotherapy, Psychiatry, RC435-571
Abstract

ABSTRACT Objective: Generalized anxiety disorder (GAD) is a chronic and disabling disorder associated with various impairments and shows a significant prevalence in the worldwide and Brazilian populations. This study aimed to investigate the longitudinal relationship of two symptoms relevant to the disorder (worry and depressive symptoms) in the context of a randomized clinical trial (RCT) by using a cross-lagged panel model (CLPM) analysis. Methods: A total of 92 adult patients with GAD were randomized to receive ten sessions of either acceptance‐based group behavioral therapy (ABBT) or nondirective supportive group therapy (NDST). Treatment had four time-point measures. Worries were measured using the Penn State Worry Questionnaire (PSWQ), and depression was measured using the Depression Anxiety Stress Scales (DASS-D). Results: The NDST model revealed significant paths from worry to depression (first wave) and from depression to worry (second wave). There was no other significant cross-lagged effect. These data show that there was an influence between symptoms only during one of the treatment groups, and without a homogeneous and constant pattern in any of the cross-lagged routes. Conclusion: A supportive group psychotherapy potentially interferes with the pattern of the direct relationship between worries and depressive symptoms in adults with GAD.

Published
2022
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215. Trends in Precipitation and Air Temperature Extremes and Their Relationship with Sea Surface Temperature in the Brazilian Midwest

Author

Luiz Octávio F. dos Santos, Nadja G. Machado, Marcelo S. Biudes, Hatim M. E. Geli, Carlos Alexandre S. Querino, Anderson L. Ruhoff, Israel O. Ivo, and Névio Lotufo Neto

Subjects
South America, SST anomalies, precipitation, air temperature, climate variability, Meteorology. Climatology, QC851-999
Abstract

The Brazilian Midwest has significant spatiotemporal variability in terms of precipitation and air temperature, making it more vulnerable to the occurrence of extreme weather events. The objective of this study is to characterize the trend of extreme climatic events regarding precipitation and air temperature in the Brazilian Midwest, and to analyze their relationship with Pacific and Atlantic Sea Surface Temperature anomalies (SSTAs). We used daily precipitation and air temperature data measured at 24 conventional weather stations. Pacific and Atlantic SSTA data were obtained from the Climate Prediction Center. The frequency of hot extremes had increased, while that of cold extremes had decreased significantly, thus highlighting the consistent warming across the Brazilian Midwest. The precipitation extremes had greater variability than the temperature extremes. Precipitation intensity increased in Amazonia, with no change in annual precipitation volume. The precipitation extremes in the Brazilian Savanna, Pantanal, and the Atlantic Forest did not have a well-defined pattern but indicated a trend towards a decrease in days with intense precipitation events. In general, the Equatorial Pacific and Atlantic Ocean (TNAI and TSAI) SSTAs were negatively correlated with precipitation extreme indices and positively correlated with air temperature extreme indices in the Amazon. However, the North Atlantic SSTAs were positively correlated with precipitation and air temperature extreme indices in the Brazilian Savanna and Pantanal. In addition, the Pacific SSTAs were positively correlated with precipitation intensity in the Atlantic Forest. Thus, the variability of the trends of precipitation and air temperature extreme indices in the Brazilian Midwest was observed, and it was surmised that this measure was significantly related to Pacific and Atlantic SSTAs.

Published
2023
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216. Prevalence and predictors of under or overestimation sleep duration in adults: The ELSA-Brasil study

Author

Ronaldo B. Santos, Soraya Giatti, Aline N. Aielo, Wagner A. Silva, Barbara K. Parise, Lorenna F. Cunha, Silvana P. Souza, Airlane P. Alencar, Paulo A. Lotufo, Isabela M. Bensenor, and Luciano F. Drager

Subjects
Sleep apnea, Sleep duration, Epidemiology, Actigraphy, Measurement error, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Objective: Every one-hour change in sleep duration (SDUR) has a dose-response impact on cardiovascular disease and mortality. However, self-reported SDUR may not represent the real sleep time in a significant proportion of the adult population. This study was designed to determine the frequency of potential SDUR under/overestimation when comparing subjective versus objective SDUR data. Methods: Consecutive adults from the ELSA-Brasil study collected subjective SDUR and underwent wrist actigraphy for seven days. We defined SDUR underestimation (underSDUR) and overestimation (overSDUR) when the differences between subjective and objective SDUR reached at least -1/+1-hour, respectively. We performed multinomial logistic regression analyses to identify independent factors of under- and overSDUR. Results: Data from 2,036 participants were used in the final analysis (42.7% males; age: 49±8 years). The frequency of underSDUR and overSDUR were 19.4% and 19.7%, respectively. The predictors of underSDUR included black race (OR: 1.65; 95% CI: 1.79–3.93), mixed-race (OR: 1.69; 95% CI: 1.20–2.38); daytime sleepiness (OR: 1.37; 95% CI: 1.05–1.80); longer objective SDUR (OR: 3.00; 95% CI: 2.54–3.56); longer wake time after sleep onset time, WASO (OR: 2.19; 95% CI: 1.22–3.95), and moderate/severe insomnia (OR: 2.54; 95% CI: 1.78–3.63). Longer WASO (OR: 2.26; 95% CI: 1.33–3.82), and a higher number of awakenings (OR: 1.02; 95% CI: 1.00–1.03) were independently associated with overSDUR. Conclusions: We found a significant rate of SDUR under/overestimation when comparing subjective versus objective data. While underSDUR was independently associated with black/mixed race, daytime sleepiness, longer SDUR and WASO, overSDUR was specifically associated with markers of sleep fragmentation.

Published
2021
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217. Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Author

Rodrigo M. Carrillo-Larco, Dalia Stern, Ian R. Hambleton, Anselm Hennis, Mariachiara Di Cesare, Paulo Lotufo, Catterina Ferreccio, Vilma Irazola, Pablo Perel, Edward W Gregg, J. Jaime Miranda, Majid Ezzati, Goodarz Danaei, Carlos A Aguilar-Salinas, Ramón Alvarez-Váz, Marselle B Amadio, Cecilia Baccino, Claudia Bambs, João Luiz Bastos, Gloria Beckles, Antonio Bernabe-Ortiz, Carla DO Bernardo, Katia V. Bloch, Juan E. Blümel, Jose G. Boggia, Pollyanna K. Borges, Miguel Bravo, Gilbert Brenes-Camacho, Horacio A Carbajal, Maria S. Castillo Rascon, Blanca H. Ceballos, Veronica Colpani, Jackie A Cooper, Sandra Cortes, Adrian Cortes-Valencia, Roberto S Cunha, Eleonora d'Orsi, William H Dow, Walter G Espeche, Flavio D. Fuchs, Sandra C. Fuchs, Suely GA Gimeno, Donaji Gomez-Velasco, David A Gonzalez-Chica, Clicerio Gonzalez-Villalpando, María-Elena Gonzalez-Villalpando, Gonzalo Grazioli, Ricardo O. Guerra, Laura Gutierrez, Fernando L Herkenhoff, Andrea RVR Horimoto, Andrea Huidobro, Elard Koch, Martin Lajous, Maria Fernanda Lima-Costa, Ruy Lopez-Ridaura, Alvaro CC Maciel, Betty S Manrique-Espinoza, Larissa P Marques, Jose G Mill, Leila B Moreira, Oscar M Muñoz, Lariane M Ono, Karen Oppermann, Karina M. Paiva, Sergio V. Peixoto, Alexandre C. Pereira, Karen G. Peres, Marco A. Peres, Paula Ramírez-Palacios, Cassiano R Rech, Berenice Rivera-Paredez, Nohora I Rodriguez, Rosalba Rojas-Martinez, Luis Rosero-Bixby, Adolfo Rubinstein, Alvaro Ruiz-Morales, Martin R Salazar, Aaron Salinas-Rodriguez, Jorge Salmerón, Ramon A Sanchez, Nelson AS Silva, Thiago LN Silva, Liam Smeeth, Poli M Spritzer, Fiorella Tartaglione, Jorge Tartaglione, and Rafael Velázquez-Cruz

Subjects
Public aspects of medicine, RA1-1270
Abstract

ABSTRACT: Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains unknown. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n=168,287) and non-fatal (13 cohorts, n=27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 100,000 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those estimated from cohorts in high-income countries. Funding: Wellcome Trust (214185/Z/18/Z)

Published
2021
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218. Association of sleep disturbances with sarcopenia and its defining components: the ELSA-Brasil study

Author

C. Szlejf, C.K. Suemoto, L.F. Drager, R.H. Griep, M.J.M. Fonseca, M.F.H.S. Diniz, P.A. Lotufo, and I.M. Benseãor

Subjects
Body composition, Insomnia, Muscle strength, Obstructive sleep apnea, Sarcopenia, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Sarcopenia and sleep problems share common physiopathology. We aimed to investigate the association of sleep disturbances with sarcopenia and its defining components in Brazilian middle-aged and older adults. In this cross-sectional analysis of the second wave of the ELSA-Brasil study, we included data from 7948 participants aged 50 years and older. Muscle mass was evaluated by bioelectrical impedance analysis and muscle strength by hand-grip strength. Sarcopenia was defined according to the Foundation for the National Institutes of Health criteria. Sleep duration and insomnia complaint were self-reported. Short sleep duration was considered as ≤6 h/night and long sleep duration as >8 h/night. High risk of obstructive sleep apnea (OSA) was assessed using the STOP-Bang questionnaire. Possible confounders included socio-demographic characteristics, lifestyle, clinical comorbidities, and use of sedatives and hypnotics. The frequencies of sarcopenia, low muscle mass, and low muscle strength were 1.6, 21.1, and 4.1%, respectively. After adjustment for possible confounders, high risk of OSA was associated with low muscle mass (OR=2.17, 95%CI: 1.92-2.45). Among obese participants, high risk of OSA was associated with low muscle strength (OR=1.68, 95%CI: 1.07-2.64). However, neither short nor long sleep duration or frequent insomnia complaint were associated with sarcopenia or its defining components. In conclusion, high risk of OSA was associated with low muscle mass in the whole sample and with low muscle strength among obese participants. Future studies are needed to clarify the temporal relationship between both conditions.

Published
2021
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219. Associations between Periodontitis, COVID-19, and Cardiometabolic Complications: Molecular Mechanisms and Clinical Evidence

Author

Giuseppe Mainas, Luigi Nibali, Mark Ide, Wael Al Mahmeed, Khalid Al-Rasadi, Kamila Al-Alawi, Maciej Banach, Yajnavalka Banerjee, Antonio Ceriello, Mustafa Cesur, Francesco Cosentino, Alberto Firenze, Massimo Galia, Su-Yen Goh, Andrej Janež, Sanjay Kalra, Nitin Kapoor, Peter Kempler, Nader Lessan, Paulo Lotufo, Nikolaos Papanas, Ali A. Rizvi, Amirhossein Sahebkar, Raul D. Santos, Anca P. Stoian, Peter P. Toth, Vijay Viswanathan, and Manfredi Rizzo

Subjects
periodontitis, periodontal diseases, COVID-19, SARS-CoV-2, comorbidity, risk, Microbiology, QR1-502
Abstract

Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.

Published
2022
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220. Efficient Methodology for Detection and Classification of Short-Circuit Faults in Distribution Systems with Distributed Generation

Author

Andréia da Silva Santos, Lucas Teles Faria, Mara Lúcia M. Lopes, Anna Diva P. Lotufo, and Carlos R. Minussi

Subjects
distribution systems, distributed generation, fuzzy logic inference, wavelet transform, multi-resolution analysis, short-circuit fault detection, Chemical technology, TP1-1185
Abstract

Fault detection and classification are crucial procedures for electric power distribution systems because they can minimize the occurrence of faults. The methods for fault detection and classification have become more problematic because of the significant expansion of distributed energy resources in distribution systems and the change in their currents due to the action of short-circuiting. In this context, to fill this gap, this study presents a robust methodology for short-circuit fault detection and classification with the insertion of distributed generation units. The proposal methodology progresses in two stages: in the former stage, the detection is based on the continuous analysis of three-phase currents, whose characteristics are extracted through maximal overlap discrete wavelet transform. In the latter stage, the classification is based on three fuzzy inference systems to identify the phases with disturbance. The short-circuit type is identified by counting the shorted phases. The algorithm for short-circuit fault detection and classification is developed in MATLAB programming environment. The methodology is implemented in a modified IEEE 34-bus test system and modeled in ATPDraw with three scenarios with and without distributed generation units and considering the following parameters: fault type (single-phase, two-phase, and three-phase), angle of incidence, fault resistance (high impedance fault and low impedance fault), fault location bus, and distributed generation units (synchronous generators and photovoltaic panels). The accuracy is greater than 94.9% for the detection and classification of short-circuit faults for more than 20,000 simulated cases.

Published
2022
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222. Global Burden of Cardiovascular Diseases and Risks, 1990-2022

Author

Mensah, G, Fuster, V, Murray, C, Roth, G, Abate, Y, Abbasian, M, Abd-Allah, F, Abdollahi, A, Abdollahi, M, Abdulah, D, Abdullahi, A, Abebe, A, Abedi, A, Abiodun, O, Ali, H, Abu-Gharbieh, E, Abu-Rmeileh, N, Aburuz, S, Abushouk, A, Abu-Zaid, A, Adane, T, Adderley, N, Adebayo, O, Aden, B, Adeyeoluwa, T, Adeyomoye, O, Sakilah Adnani, Q, Afrashteh, F, Afyouni, S, Afzal, S, Agasthi, P, Agodi, A, Aguilera Arriagada, C, Agyemang-Duah, W, Ahinkorah, B, Ahmad, A, Ahmad, D, Ahmad, F, Ahmad, M, Ahmed, A, Ahmed, H, Ahmed, M, Ahmed, S, Ajami, M, Akinosoglou, K, Ala, M, Ali AL-Ahdal, T, Alalalmeh, S, Al-Aly, Z, Alam, N, Al-amer, R, Alashi, A, Albashtawy, M, Albataineh, M, Alema, H, Alemi, S, Alemu, Y, Saeed Al-Gheethi, A, Alhabib, K, Naji Alhalaiqa, F, Ali, M, Ali, R, Pursuing, P, Shujait Ali, S, Alicandro, G, Alikhani, R, Aljunid, S, Alla, F, Almahmeed, W, Al-Marwani, S, Alonso, J, Al-Raddadi, R, Alvi, F, Alvis-Guzman, N, Alvis-Zakzuk, N, Alwafi, H, Aly, H, Amegbor, P, Amin, T, Amindarolzarbi, A, Amini-Rarani, M, Amiri, S, Ammirati, E, Anand, T, Ancuceanu, R, Anderlini, D, Anil, A, Ansari, G, Anyanwu, P, Anyasodor, A, Carace Apostol, G, Arabloo, J, Arafat, M, Aravkin, A, Aremu, O, Armocida, B, Arnlov, J, Arowosegbe, O, Artamonov, A, Artanti, K, Arulappan, J, Aruleba, I, Arumugam, A, Aryan, Z, Asghari-Jafarabadi, M, Astell-Burt, T, Ataei, M, Athar, M, Atreya, A, Aujayeb, A, Awotidebe, A, Aynalem, A, Azizi, Z, Azzam, A, Babu, A, Badar, M, Bader, F, Badiye, A, Bagga, A, Bagherieh, S, Asl, F, Bai, R, Baker, J, Bakkannavar, S, Bako, A, Bakshi, R, Balogun, S, Baltatu, O, Bam, K, Banach, M, Bandyopadhyay, S, Banik, B, Chandra Banik, P, Bansal, K, Baradaran, H, Barbic, F, Barchitta, M, Bardhan, M, Barker-Collo, S, Barnighausen, T, Barone-Adesi, F, Barteit, S, Barua, L, Bashiri, A, Bayati, M, Bayileyegn, N, Behboudi, E, Behnoush, A, Bejot, Y, Belay, S, Belete, M, Belgaumi, U, Bell, M, Belo, L, Bendak, S, Benfor, B, Bennett, D, Bensenor, I, Benziger, C, Beran, A, Berman, A, Bermudez, A, Bertolacci, G, Beyene, H, Beyene, K, Srikanth Bhagavathula, A, Bhardwaj, N, Bhardwaj, P, Bhat, V, Bhatti, G, Bhatti, J, Bikbov, B, Bikov, A, Birck, M, Biswas, B, Bitaraf, S, Bodunrin, A, Bogale, E, Bogale, K, Boloor, A, Hashemi, M, Borhany, H, Boyko, E, Braithwaite, D, Brant, L, Brauer, M, Breitner, S, Briko, A, Bulto, L, Bustanji, Y, Butt, Z, Calina, D, Cao, F, Cardenas, R, Carr, S, Carreras, G, Carrero, J, Carvalho, M, Castaldelli-Maia, J, Castaneda-Orjuela, C, Cattaruzza Luca Cegolon, M, Cerin, E, Chahine, Y, Kai Chan, J, Chan, M, Chan, R, Charalampous, P, Charan, J, Chattu, V, Chen, A, Chen, C, Chen, H, Chennapragada, S, Chew, D, Chi, G, Ching, P, Chitheer, A, Jemma Cho, S, Cho, W, Chong, B, Chopra, H, Choudhary, R, Chowdhury, E, Chowdhury, R, Chu, D, Chukwu, I, Giuseppe Cicero, A, Cindi, Z, Cioffi, I, Coberly, K, Coffey, S, Columbus, A, Conde, J, Conti, S, Corso, B, Cortes, S, Cortesi, P, Costa, V, Couto, R, Cowart, E, Criqui, M, Cruz, J, Dadana, S, Dadras, O, Dai, X, Dai, Z, 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Epidemiology, K, Latifinaibin, K, Lau, J, Lauriola, P, Le, K, Dao Le, L, Hanh Le, N, Thu Le, T, Thanh Le, T, Bich Le, T, Ledda, C, Lee, M, Lee, P, Lee, S, Lee, W, Lee, Y, Legrand, K, Leinsalu, M, Leonardi, M, Lerango, T, Li, A, Li, M, Li, W, Li, X, Li, Y, Lim, L, Lim, S, Lin, R, Lindstrom, M, Linn, S, Liu, G, Liu, S, Liu, X, Livingstone, K, Llanaj, E, Lopukhov, P, Sci (Med), C, Loreche, A, Lorenzovici, L, Lorkowski, S, Lotufo, P, Lucchetti, G, Lugo, A, Ma, Z, Madadizadeh, F, Maddison, R, Magana Gomez, J, Magne, J, Prasad, D, Mahalleh, M, Mahmoud, M, Mahmoudi, E, Mahmoudvand, B, Makram, O, Rad, E, Malekzadeh, R, Malhotra, K, Malik, I, Ahmed Malik, M, Mallhi, T, Malta, D, Manilal, A, Manla, Y, Mansoori, Y, Mansouri, B, Mansouri, P, Mansournia, M, Marateb, H, Marino, M, Martini, D, Martini, S, Maryam, S, Marzo, R, Masoudi, A, Masoudi, S, Matei, C, Mathangasinghe, Y, Mathews, E, Mathur, M, Mattumpuram, J, Maude, R, Maugeri, A, Mayeli, M, Mazidi, M, Mcgrath, J, Mcphail, S, Mechili, E, 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A., Fuster V., Murray C. J. L., Roth G. A., Abate Y. H., Abbasian M., Abd-Allah F., Abdollahi A., Abdollahi M., Abdulah D. M., Abdullahi A., Abebe A. M., Abedi A., Abiodun O. O., Ali H. A., Abu-Gharbieh E., Abu-Rmeileh N. M. E., Aburuz S., Abushouk A. I., Abu-Zaid A., Adane T. D., Adderley N. J., Adebayo O. M., Aden B., Adeyeoluwa T. E., Adeyomoye O. I., Sakilah Adnani Q. E., Afrashteh F., Afyouni S., Afzal S., Agasthi P., Agodi A., Aguilera Arriagada C. E., Agyemang-Duah W., Ahinkorah B. O., Ahmad A., Ahmad D., Ahmad F., Ahmad M. M., Ahmed A., Ahmed H., Ahmed M. B., Ahmed S. A., Ajami M., Akinosoglou K., Ala M., Ali AL-Ahdal T. M., Alalalmeh S. O., Al-Aly Z., Alam N., Al-amer R. M., Alashi A., Albashtawy M., AlBataineh M. T., Alema H. B., Alemi S., Alemu Y. M., Saeed Al-Gheethi A. A., Alhabib K. F., Naji Alhalaiqa F. A., Ali M. U., Ali R., pursuing P., Shujait Ali S. S., Alicandro G., Alikhani R., Aljunid S. M., Alla F., Almahmeed W., Al-Marwani S., Alonso J., Al-Raddadi R. M., Alvi F. J., Alvis-Guzman N., Alvis-Zakzuk N. J., Alwafi H., Aly H., Amegbor P. M., Amin T. T., Amindarolzarbi A., Amini-Rarani M., Amiri S., Ammirati E., Anand T., Ancuceanu R., Anderlini D., Anil A., Ansari G., Anyanwu P. E., Anyasodor A. E., Carace Apostol G. L., Arabloo J., Arafat M., Aravkin A. Y., Aremu O., Armocida B., Arnlov J., Arowosegbe O. O., Artamonov A. A., Artanti K. D., Arulappan J., Aruleba I. T., Arumugam A., Aryan Z., Asghari-Jafarabadi M., Astell-Burt T., Ataei M., Athar M., Atreya A., Aujayeb A., Awotidebe A. W., Aynalem A. A., Azizi Z., Azzam A. Y., Babu A. S., Badar M., Bader F., Badiye A. D., Bagga A., Bagherieh S., Asl F. B., Bai R., Baker J. L., Bakkannavar S. M., Bako A. T., Bakshi R. K., Balogun S. A., Baltatu O. C., Bam K., Banach M., Bandyopadhyay S., Banik B., Chandra Banik P., Bansal K., Baradaran H. R., Barbic F., Barchitta M., Bardhan M., Barker-Collo S. L., Barnighausen T. W., Barone-Adesi F., Barteit S., Barua L., Bashiri A., Bayati M., Bayileyegn N. S., Behboudi E., Behnoush A. H., Bejot Y., Belay S. A., Belete M. A., Belgaumi U. I., Bell M. L., Belo L., Bendak S., Benfor B., Bennett D. A., Bensenor I. M., Benziger C. P., Beran A., Berman A. E., Bermudez A. N. C., Bertolacci G. J., Beyene H. B., Beyene K. A., Srikanth Bhagavathula A. S., Bhardwaj N., Bhardwaj P., Bhardwaj P. V., Bhat V., Bhatti G. K., Bhatti J. S., Bikbov B., Bikov A., Birck M. G., Biswas B., Bitaraf S., Bodunrin A. O., Bogale E. K., Bogale K. A., Boloor A., Hashemi M. B., Borhany H., Boyko E. J., Braithwaite D., Brant L. C., Brauer M., Breitner S., Briko A., Bulto L. N., Bustanji Y., Butt Z. A., Calina D., Cao F., Cardenas R., Carr S., Carreras G., Carrero J. J., Carvalho M., Castaldelli-Maia J. M., Castaneda-Orjuela C. A., Cattaruzza Luca Cegolon M. S., Cerin E., Chahine Y., Kai Chan J. S., Chan M. Y., Chan R. N. C., Charalampous P., Charan J., Chattu V. K., Chen A. -T., Chen C. S., Chen H., Chennapragada S. S., Chew D. S., Chi G., Ching P. R., Chitheer A., Jemma Cho S. M., Cho W. C. S., Chong B., Chopra H., Choudhary R., Chowdhury E. K., Chowdhury R., Chu D. -T., Chukwu I. S., Giuseppe Cicero A. F., Cindi Z., Cioffi I., Coberly K., Coffey S., Columbus A., Conde J., Conti S., Corso B., Cortes S., Cortesi P. A., Costa V. M., Couto R. A. S., Cowart E. J., Criqui M. H., Cruz J. A., Dadana S., Dadras O., Dai X., Dai Z., Dalaba M. A., Moura Damasceno A. A., Damiani G., D'Amico E., Das S., Dashti M., Dashtkoohi M., Dastmardi M., Davletov K., Debele A. T., Debopadhaya S., DeCleene N. K., Delgado-Enciso I., Delgado-Saborit J. M., Demessa B. H., Demetriades A. K., Deng X., Denova-Gutierrez E., Dereje N. D., Asrat Derese A. M., Desai H. D., Desai R., Chellaiyan Devanbu V. G., Rahman Dewan S. M., Dey S., Dhulipala V. R., Diaz D., Diaz M. J., Ding D. D., Dinis-Oliveira R. J., Do T. C., Phuong Do T. H., Doaei S., Dohare S., Dong W., D'Oria M., Mombaque dos Santos W., Douiri A., Dowou R. K., Dsouza A. C., Dsouza H. L., Dsouza V., Du M., Duraes A. R., Durojaiye O. C., Dutta S., Dziedzic A. M., Ebrahimi A., Efendi D., Efendi F., Effendi D. E., Eini E., Ekholuenetale M., Ekundayo T. C., El Sayed I., El Tantawi M., Elbarazi I., Elgar F. J., Elgendy I. Y., Elhadi M., El-Huneidi W., Emamverdi M., Emeto T. I., Erkhembayar R., Eshetie T. C., Espinosa-Montero J., Etaee F., Fabin N., Fadhil I., Fagbamigbe A. F., Falzone L., Sofia e Sa Farinha C., Faris M. E. M., Faro A., Faruque M., Farwati M., Fasanmi A. O., Fatehizadeh A., Fazeli P., Feigin V. L., Feng X., Fereshtehnejad S. -M., Feroze A. H., Ferrara P., Ferreira N., Filip I., Fleszar L., Flood D., Folayan M. O., Fomenkov A. A., Fonseca D. A., Fornari C., Foschi M., Franklin R. C., Fukumoto T., BlimaFux P., Gaal P. A., Gadanya M. A., Gaidhane S., Gaipov A., Gakidou E., Galali Y., Gallus S., Gandhi A. P., Ganesan B., Gautam R. K., Gebregergis M. W. W., Gebrekidan K. G., Geleijnse J. M., Gerema U., Ghajar A., Ghamari S. -H., Ghasemi M., Dabaghi G. G., Ghasemzadeh A., Ghazy R. M., Gholamalizadeh M., Ghuge A. D., Gill P. S., Gill T. K., Gillum R. F., Gnedovskaya E. V., Golchin A., Goleij P., Gorini G., Goulart A. C., Goyal A., Goyal K., Guan S. -Y., Guarducci G., Gudeta M. D., Guha A., Guicciardi S., Gulisashvili D., Gunawardane D. A., Guo C., Gupta A. K., Gupta B., Gupta I. R., Gupta K., Gupta M., Gupta R. D., Gupta R., Gupta S., Gupta V. B., Gupta V. K., Gurmessa L., Gutierrez R. A., Habibzadeh F., Hadei M., Haeri Boroojeni H. S., Halimi A., Haller S., Halwani R., Hamadeh R. R., Hamdy N. M., Hamidi S., Han C., Han Q., Hankey G. J., Hannan M. A., Hargono A., Haro J. M., Hasan F., Hasan I., Hasani H., Hashemian M., Hasnain M. S., Hassan A., Hassan I., Haubold J., Havmoeller R. J., Hay S. I., Hayat K., Hbid Y., Hegazi O. E., Hegena T. Y., Heidari M., Helfer B., Herrera-Serna B. Y., Herteliu C., Hesami H., Hessami K., Heydari K., Hezam K., Hiraike Y., Hoan N. Q., Holla R., Hossain M. M., Hossain M. B., Hosseinzadeh H., Hosseinzadeh M., Hostiuc M., Hostiuc S., Hsairi M., Huang J., Hultstrom M., Huynh H. -H., Hwang B. -F., Ibrahim K. S., Idowu O. O., Ilesanmi O. S., Ilic I. M., Ilic M. D., Immurana M., Inbaraj L. R., Iqhrammullah M., Shariful Islam S. M., Ismail F., Ismail N. E., Isola G., Iwagami M., J L. M., Jaafari J., Jacob L., Jafarzadeh A., Jaggi K., Jahrami H., Jain A., Jain N., Jairoun A. A., Jakovljevic M., Jamora R. D. G., Javadi N., Jayapal S. K., Jayaram S., Jebai R., Jeben R. S., Jee S. H., Jha A. K., Jha R. P., Jha V., Jiang H., Jin Y., Jobanputra Y. B., Johnson C. O., Jokar M., Joo T., Joseph A., Joseph N., Joshua C. E., Jozwiak J. J., Jurisson M., Kabir A., Kabir Z., Kadashetti V., Kahe F., Kalani R., Kalankesh L. R., Kalantar F., Kalkonde Y., Kalra S., Kamath A., Kamath S., Kamireddy A., Kanchan T., Kandel H., Kanmanthareddy A. R., Kanmodi K. K., Kansal S. K., Kapner D. J., Kar S. S., Karakasis P., Karki P., Kashoo F. Z., Kasraei H., Kassahun E. A., Kassebaum N. J., Katoto P. D. M. C., Kaydi N., Kazemi F., Kazemian S., Kazeminia S., Kerr J. A., Kesse-Guyot E., Keykhaei M., Khadembashiri M. M., Khadembashiri M. A., Khafaie M. A., Khajuria H., Khalaji A., Khalid N., Khalilian A., Khalilov R., Khan A., Khan E. A., Khan J., Khan M. N., Khan M., Khan M. J., Khan M. S., Khan Y. H., Khan suheb M. Z., Khanmohammadi S., Khatab K., Khateri S., Khayat Kashani H. R., Kheirallah K. A., Khidri F. F., Kian S., Kifle Z. D., Kimokoti R. W., Kisa A., Kisa S., Kolahi A. -A., Kompani F., Koren G., Kotnis A. L., Koul P. A., Koyanagi A., Krishan K., Krishna H., Krishnamoorthy V., Krishnamoorthy Y., Kuddus M. A., Kuddus M., Kulimbet M., Kulkarni V., Kumar A., Kumar N., Kumar R., Kumsa N. B., Kunle K. R., Kusuma D., Kyriopoulos I., La Vecchia C., Lacey B., Ladan M. A., Laflamme L., Lahariya C., Lahiri A., Ching Lai D. T., Lallukka T., Lan Q., Landires I., Lanfranchi F., Larijani B., Larsson A. O., Lasrado S., Latief Epidemiology K., Latifinaibin K., Lau J., Lauriola P., Le K., Dao Le L. K., Hanh Le N. H., Thu Le T. T., Thanh Le T. D., Bich Le T. T., Ledda C., Lee M., Lee P. H., Lee S. W., Lee W. -C., Lee Y. H., LeGrand K. E., Leinsalu M., Leonardi M., Lerango T. L., Li A., Li M. -C., Li W., Li X., Li Y., Lim L. -L., Lim S. S., Lin R. -T., Lindstrom M., Linn S., Liu G., Liu S., Liu X., Livingstone K. M., Llanaj E., Lopukhov P. D., Sci (Med) C. O., Loreche A. M., Lorenzovici L., Lorkowski S., Lotufo P. A., Lucchetti G., Lugo A., Ma Z. F., Madadizadeh F., Maddison R., Magana Gomez J. A., Magne J., Prasad D. R. M., Mahalleh M., Mahmoud M. A., Mahmoudi E., Mahmoudvand B., Makram O. M., Rad E. M., Malekzadeh R., Malhotra K., Malik I., Ahmed Malik M. S., Mallhi T. H., Malta D. C., Manilal A., Manla Y., Mansoori Y., Mansouri B., Mansouri P., Mansournia M. A., Marateb H. R., Marino M., Martini D., Martini S., Maryam S., Marzo R. R., Masoudi A., Masoudi S., Matei C. N., Mathangasinghe Y., Mathews E., Mathur M. R., Mattumpuram J., Maude R. J., Maugeri A., Mayeli M., Mazidi M., McGrath J. J., McPhail S. M., Mechili E. A., Carabeo Medina J. R., Meena J. K., Mehrabani-Zeinabad K., Mendez Mendez-Lopez M. A., Mendoza W., Menezes R. G., Mengist B., Meo S. A., Meresa H. A., Meretoja A., Meretoja T. J., Mestrovic T., Dinushi Mettananda K. C., Mettananda S., Mhlanga L., Mi T., Jonasson J. M., Miazgowski T., Michalek I. M., Miller T. R., Nhat Minh L. H., Minja N. W., Mohammad Sadeghi P. M., Mirdamadi N., Mirica A., Mirrakhimov E. M., Mirza M., Mirza-Aghazadeh-Attari M., Mithra P., Moghimi Z., Mohamed J., Mohamed M. F. H., Mohamed N. S., Mohammadi S., Mohammed H., Mohammed M., Mohammed S., Moka N., Mokdad A. H., Vardanjani H. M., Momtazmanesh S., Monasta L., Montazeri F., Ghalibaf A. M., Moradi Y., Moraga P., Morawska L., Morovatdar N., Morrison S. D., Morze J., Mostafavi E., Mostofinejad A., Mougin V., Mousavi P., Mousavi S. E., Mozaffarian D., Msherghi A., Muccioli L., Mueller U. O., Mukherjee S., Munjal K., Murillo-Zamora E., Mustafa G., Muthu S., Mwita J. C., Myung W., Nagarajan A. J., Nagaraju S. P., Naik G. R., Naik G., Nair T. S., Najafi M. S., Ansari N. N., Nangia V., Swamy S. N., Nargus S., Nascimento B. R., Nascimento G. G., Nasoori H., Natto Z. S., Nauman J., Naveed M., Nayak B. P., Nayak V. C., Negash H., Negoi I., Negoi R. I., Shahrokh Abadi R. N., Nejadghaderi S. A., Nejjari C., Nematollahi M. H., Nepal S., Ng N., Nguyen D. H., Nguyen P. T., Nguyen V. T., Niazi R. K., Nijjar S. S., Nizam M. A., Noman E. A., Nomura S., Noreen M., Norrving B., Noubiap J. J., Nri-Ezedi C. A., Ntsekhe M., Nurrika D., Nzoputam C. I., Nzoputam O. J., Obamiro K. O., O'Donnell M. J., Oghenetega O. B., Oguntade A. S., Oguta J. O., Okeke S. R., Okekunle A. P., Okidi L., Okonji O. C., Okwute P. G., Olagunju A. T., Olaiya M. T., Olana M. D., Olatubi M. I., Moraes Oliveira G. M., Olorukooba A. A., Olufadewa I. I., Oluwafemi Y. D., Oluwatunase G. O., Omer G. L., Ommati M. M., Ong K. L., Ong S., Onyedibe K. I., Ordak M., Ortega-Altamirano D. V., Ortiz A., Ortiz-Prado E., Osman W. M. S., Osuagwu U. L., Otoiu A., Otstavnov S. S., Owolabi M. O., Padukudru P A M., Padron-Monedero A., Padubidri J. R., Varnosfaderani M. P., Palicz T., Palladino R., Pan F., Pan H. -F., Pandi-Perumal S. R., Papadopoulou P., Park S., Passera R., Patel J., Patil S., Patoulias D., Patthipati V. S., Pawar S., Peden A. E., Pedersini P., Peng M., Filipino Pepito V. C., Peprah E. K., Pereira M., Pereira M. O., Peres M. F. P., Perianayagam A., Perico N., Petermann-Rocha F. E., Pham H. T., Philip A. K., Pigott D. M., Pilgrim T., Piradov M. A., Plotnikov E., Poddighe D., Polibin R. V., Poluru R., Pourali G., Pourshams A., Singh Pradhan P. M., Prasad M., Sady Prates E. J., Purohit B. M., Puvvula J., Qattea I., Qian G., Qureshi M. F., Rabiee rad M., Radfar A., Rafiei Alavi S. N., Rafique I., Raggi A., Rahim F., Rahim M. J., Rahimi M., Rahman M., Rahman M. A., Rahmani A. M., Rahmani B., Rahmani S., Rahmanian V., Rai P., Rajaa S., Rajabpour-Sanati A., Rajput P., Ram P., Ramalingam S., Ramasamy S. K., Ramazanu S., Ramesh P. S., Rana J., Rana K., Ranabhat C. L., Rancic N., Rane A., Ranjan S., Ranta A., Rao I. R., Rao M., Rao S. J., Rashedi S., Rashedi V., Rashid A. M., Rasul A., Ratan Z. A., Babu G. R., Ravikumar N., Rawaf S., Razeghian-Jahromi I., Razo C., Rama Krishna Reddy M. M., Mohamed Redwan E. M., Remuzzi G., Reyes L. F., Rezaei N., Rezaeian M., Ribeiro A. L. P., Ribeiro D., Rikhtegar R., Roever L., Romadlon D. S., Ronfani L., Sekhar Rout H. S., Roy N., Roy P., Rynkiewicz A., Saad A. M. A., Saadatian Z., Sabour S., Sacco S., Sachdeva R., Saddik B., Sadeghi E., Saeed U., Safaeinejad F., Sharif-Askari F. S., Sharif-Askari N. S., Sahebkar A., Sahoo S. S., Sajedi S. A., Sajid M. R., Sakshaug J. W., Salam N., Salami A. A., Saleh M. A., Salehi S., Salem M. R., Salem M. Z. Y., Samadzadeh S., Samargandy S., Samuel V. P., Samy A. M., Sanabria J., Sanjeev R. K., Santric-Milicevic M. M., Nadeem Saqib M. A., Sarasmita M. A., Saravanan A., Sarikhani Y., Sarkar T., Sarmiento-Suarez R., Sarode G. S., Sarode S. C., Sathish T., Sathyanarayan A., Sawhney M., Sayyah M., Scarmeas N., Schaarschmidt B. M., Schuermans A., Schumacher A. E., Schutte A. E., Schwebel D. C., Sedighi M., Seidu A. -A., Semnani F., Senapati S., Sengupta P., Senthilkumaran S., Sepanlou S. G., Sethi Y., Seyedi S. A., Seylani A., Shabany M., Shafeghat M., Shafie M., Shah P. A., Shahbandi A., Shahid I., Shahid S., Shahid W., Shahwan M. J., Shaikh M. A., Sham S., Shamim M. A., Shanawaz M., Sharfaei S., Sharifan A., Sharifi-Rad J., Sharma P., Sharma S., Sharma U., Sharma V., Sheikh A., Shiferaw D. S., Shigematsu M., Shin M. -J., Shiri R., Shishani K., Shittu A., Shiue I., Shivakumar K. M., Shrestha S., Shuval K., Sibhat M. M., Sigfusdottir I. D., Simpson C. R., Singh A., Singh J. A., Singh P., Singh R., Singh S., Siraj M. S., Skryabin V. Y., Skryabina A. A., Sleet D. A., Soleimani H., Solikhah S., Soliman S. S. M., Son J., Song S., Song Y., Soriano J. B., Spartalis M., Sreeramareddy C. T., Stafford L. K., Stark B. A., Steiropoulos P., Stortecky S., Abdulkader R. S., Sultana A., Sundstrom J., Swain C. K., Damavandi P. T., Tabatabaei S. M., Malazy O. T., Tabatabaeizadeh S. -A., Tabatabai S., Tabb K. M., Tabish M., Tabuchi T., Tadese F., Abkenar Y. T., Taiba J., Talaat I. M., Tampa M., Lukenze Tamuzi J. J. L., Tan K. -K., Tang H., Tarkang E. E., Tat N. Y., Tavangar S. M., Tehrani H., Teimoori M., Temsah M. -H., Hani Temsah R. M., Teramoto M., Thangaraju P., Thankappan K. R., Thapa R., Thapar R., Thavamani A., Thayakaran R., Thomas N. K., Tian J., Tichopad A., Tillawi T., Tonelli M., Topor-Madry R., Touvier M., Tovani-Palone M. R., Tran J. T., Tran N. M., Van Tran P., Trihandini I., Tripathi A., Tromans S. J., Truong V. T., Tri Tai Truyen T. T., Tsatsakis A., Tsegay G. M., Tsermpini E. E., Tumurkhuu M., Tung K., Ubah C. S., Udoakang A. J., Udoh A., Ullah A., Ullah S., Umair M., Umar T. P., Unim B., Unnikrishnan B., Upadhyay E., Usman J. S., Vahabi S. M., Vaithinathan A. G., Valizadeh R., Van den Eynde J., Varga O., Varma S. A., Vart P., Varthya S. B., Vasankari T. J., Vellingiri B., Vervoort D., Villafane J. H., Violante F. S., Viskadourou M., Volovat S. R., Vos T., Vujcic I. S., Wafa H. A., Wahab F., Wang C., Wang F., Wang N., Wang S., Wang Y., Wang Y. -P., Wei M. Y., Werdecker A., Wickramasinghe N. D., Wijeratne T., Wilandika A., Wilson S., Wolfe C. D. A., Wongsin U., Wu Z., Xiao H., Xu S., Xu X., Yadav L., Yano Y., Yaribeygi H., Yasufuku Y., Nia I. Y., Ye P., Yesuf S. A., Yezli S., Yigit A., Yigit V., Yilma M. T., Yon D. K., Yonemoto N., Yousefi Z., Yperzeele L., Yu C., Yunusa I., Zafari N., Tajrishi F. Z., Zakham F., Zastrozhin M. S., Zeineddine M. A., Zemedikun D. T., Zeng Y., Zhai C., Zhang C., Zhang H., Zhang L., Zhang N., Zhang Y., Zhao H., Zheng P., Zhong C., Zhou S., Zhu B., Zhu L., Zielinska M., Zikarg Y. T., Zmaili M., Zoeckler L. Z., Zou Z., Zumla A., Zweck E., and Zyoud S. H.

Published
2023

223. Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission

Author

Feigin, V, Owolabi, M, Abd-Allah, F, Akinyemi, R, Bhattacharjee, N, Brainin, M, Cao, J, Caso, V, Dalton, B, Davis, A, Dempsey, R, Duprey, J, Feng, W, Ford, G, Gall, S, Gandhi, D, Good, D, Hachinski, V, Hacke, W, Hankey, G, Ishida, M, Johnson, W, Kim, J, Lavados, P, Lindsay, P, Mahal, A, Martins, S, Murray, C, Nguyen, T, Norrving, B, Olaiya, M, Olalusi, O, Pandian, J, Phan, H, Platz, T, Ranta, A, Rehman, S, Roth, G, Sebastian, I, Smith, A, Suwanwela, N, Sylaja, P, Thapa, R, Thrift, A, Uvere, E, Vollset, S, Yavagal, D, Yaria, J, Abera, S, Ibrahim, N, Liu, L, Ovbiagele, B, Piradov, M, Abanto, C, Addissie, A, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Akhmetzhanova, Z, Akpalu, A, El Alaoui-Faris, M, Ameriso, S, Andonova, S, Arsovska, A, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bereczki, D, Beretta, S, Berkowitz, A, Bernhardt, J, Berzina, G, Bhavsar, B, Bisharyan, M, Bohara, M, Bovet, P, Budincevic, H, Cadilhac, D, Cerimagic, D, Charway-Felli, A, Chen, C, Chin, J, Christensen, H, Chwojnicki, K, Conforto, A, Correia, M, Mora Cuervo, D, Czlonkowska, A, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Demchuk, A, Dichgans, M, Dokova, K, Donnan, G, Duran, J, Ekeng, G, Elkind, M, Endres, M, Fischer, U, Flomin, Y, Gankpe, F, Gavidia, M, Gaye Saavedra, A, Gebreyohanns, M, George, M, Gierlotka, M, Giroud, M, Gnedovskaya, E, Goncalves, I, Gongora-Rivera, F, Gunaratne, P, Hamadeh, R, Hamzat, T, Heldner, M, Ibrahim, E, Ihle-Hansen, H, Jee, S, Jiann-Shing, J, Johnston, S, Jovanovic, D, Jurjans, K, Kalani, R, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Kiechl, S, Kondybayeva, A, Korv, J, Kozera, G, Kravchenko, M, Krespi, Y, Krishnamurthi, R, Kruja, J, Kutluk, K, Langhorne, P, Law, Z, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, M, Maia, L, Malojcic, B, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Miglane, E, Mihejeva, I, Mikulik, R, Mirrakhimov, E, Mohl, S, Munakomi, S, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ocampo, C, O'Donnell, M, Ogun, Y, Ogunniyi, A, Oraby, M, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Pereira, T, Peeters, A, Potpara, T, Proios, H, Rathore, F, Sacco, R, Sahathevan, R, Sandset, E, Renato Santos, I, Saposnik, G, Sarfo, F, Sargento-Freitas, J, Sharma, M, Shaw, L, Sheth, K, Shin, Y, Shobhana, A, Silva, S, Tedim Cruz, V, Thakur, K, Thapa, L, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, J, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wojtyniak, B, Wolfe, C, Yacouba, M, Yang, J, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zagozdzon, P, Feigin V. L., Owolabi M. O., Abd-Allah F., Akinyemi R. O., Bhattacharjee N. V., Brainin M., Cao J., Caso V., Dalton B., Davis A., Dempsey R., Duprey J., Feng W., Ford G. A., Gall S., Gandhi D., Good D. C., Hachinski V., Hacke W., Hankey G. J., Ishida M., Johnson W., Kim J., Lavados P., Lindsay P., Mahal A., Martins S., Murray C., Nguyen T. P., Norrving B., Olaiya M. T., Olalusi O. V., Pandian J., Phan H., Platz T., Ranta A., Rehman S., Roth G., Sebastian I. A., Smith A. E., Suwanwela N. C., Sylaja P. N., Thapa R., Thrift A. G., Uvere E., Vollset S. E., Yavagal D., Yaria J., Abera S. F., Akinyemi R., Dempsey R. J., Ibrahim N. M., Liu L., Ovbiagele B., Piradov M., Suwanwela N., Abanto C., Addissie A., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Akhmetzhanova Z., Akpalu A., El Alaoui-Faris M., Ameriso S. F., Andonova S., Arsovska A., Awoniyi F. E., Bakhiet M., Barboza M. A., Basri H., Bath P. M., Bereczki D., Beretta S., Berkowitz A. L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M. S., Bohara M., Bovet P., Budincevic H., Cadilhac D. A., Cerimagic D., Charway-Felli A., Chen C., Chin J. H., Christensen H., Chwojnicki K., Conforto A. B., Correia M., Mora Cuervo D. L., Czlonkowska A., D'Amelio M., Danielyan K. E., Davis S., Demarin V., Demchuk A. M., Dichgans M., Dokova K., Donnan G., Duran J. C., Ekeng G., Elkind M. S., Endres M., Fischer U., Flomin Y., Gankpe F., Gavidia M., Gaye Saavedra A., Gebreyohanns M., George M., Gierlotka M., Giroud M., Gnedovskaya E. V., Goncalves I. P., Gongora-Rivera F., Gunaratne P. S., Hamadeh R. R., Hamzat T. -H. K., Heldner M. R., Ibrahim E., Ihle-Hansen H., Jee S., Jiann-Shing J., Johnston S. C., Jovanovic D., Jurjans K., Kalani R., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Kiechl S., Kondybayeva A., Korv J., Kozera G., Kravchenko M., Krespi Y., Krishnamurthi R., Kruja J., Kutluk K., Langhorne P., Law Z. K., Lebedynets D., Lee T. -H., Leung T. W., Liebeskind D. S., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion M. J., Maia L. F., Malojcic B., Markus H. S., Marquez-Romero J. M., Medina M. T., Medukhanova S., Mehndiratta M. M., Miglane E., Mihejeva I., Mikulik R., Mirrakhimov E., Mohl S., Munakomi S., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C. H., Noubiap J. J., Novarro-Escudero N., Ocampo C., O'Donnell M., Ogun Y., Ogunniyi A., Oraby M. I., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Pereira T., Peeters A., Potpara T., Proios H., Rathore F. A., Sacco R. L., Sahathevan R., Sandset E. S., Renato Santos I., Saposnik G., Sarfo F. S., Sargento-Freitas J., Sharma M., Shaw L., Sheth K. N., Shin Y. -I., Shobhana A., Silva S. N., Tedim Cruz V., Thakur K., Thapa L. J., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tulloch-Reid M., Useche J. N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wojtyniak B., Wolfe C., Yacouba M. N., Yang J., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., Zagozdzon P., Feigin, V, Owolabi, M, Abd-Allah, F, Akinyemi, R, Bhattacharjee, N, Brainin, M, Cao, J, Caso, V, Dalton, B, Davis, A, Dempsey, R, Duprey, J, Feng, W, Ford, G, Gall, S, Gandhi, D, Good, D, Hachinski, V, Hacke, W, Hankey, G, Ishida, M, Johnson, W, Kim, J, Lavados, P, Lindsay, P, Mahal, A, Martins, S, Murray, C, Nguyen, T, Norrving, B, Olaiya, M, Olalusi, O, Pandian, J, Phan, H, Platz, T, Ranta, A, Rehman, S, Roth, G, Sebastian, I, Smith, A, Suwanwela, N, Sylaja, P, Thapa, R, Thrift, A, Uvere, E, Vollset, S, Yavagal, D, Yaria, J, Abera, S, Ibrahim, N, Liu, L, Ovbiagele, B, Piradov, M, Abanto, C, Addissie, A, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Akhmetzhanova, Z, Akpalu, A, El Alaoui-Faris, M, Ameriso, S, Andonova, S, Arsovska, A, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bereczki, D, Beretta, S, Berkowitz, A, Bernhardt, J, Berzina, G, Bhavsar, B, Bisharyan, M, Bohara, M, Bovet, P, Budincevic, H, Cadilhac, D, Cerimagic, D, Charway-Felli, A, Chen, C, Chin, J, Christensen, H, Chwojnicki, K, Conforto, A, Correia, M, Mora Cuervo, D, Czlonkowska, A, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Demchuk, A, Dichgans, M, Dokova, K, Donnan, G, Duran, J, Ekeng, G, Elkind, M, Endres, M, Fischer, U, Flomin, Y, Gankpe, F, Gavidia, M, Gaye Saavedra, A, Gebreyohanns, M, George, M, Gierlotka, M, Giroud, M, Gnedovskaya, E, Goncalves, I, Gongora-Rivera, F, Gunaratne, P, Hamadeh, R, Hamzat, T, Heldner, M, Ibrahim, E, Ihle-Hansen, H, Jee, S, Jiann-Shing, J, Johnston, S, Jovanovic, D, Jurjans, K, Kalani, R, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Kiechl, S, Kondybayeva, A, Korv, J, Kozera, G, Kravchenko, M, Krespi, Y, Krishnamurthi, R, Kruja, J, Kutluk, K, Langhorne, P, Law, Z, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, M, Maia, L, Malojcic, B, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Miglane, E, Mihejeva, I, Mikulik, R, Mirrakhimov, E, Mohl, S, Munakomi, S, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ocampo, C, O'Donnell, M, Ogun, Y, Ogunniyi, A, Oraby, M, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Pereira, T, Peeters, A, Potpara, T, Proios, H, Rathore, F, Sacco, R, Sahathevan, R, Sandset, E, Renato Santos, I, Saposnik, G, Sarfo, F, Sargento-Freitas, J, Sharma, M, Shaw, L, Sheth, K, Shin, Y, Shobhana, A, Silva, S, Tedim Cruz, V, Thakur, K, Thapa, L, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, J, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wojtyniak, B, Wolfe, C, Yacouba, M, Yang, J, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zagozdzon, P, Feigin V. L., Owolabi M. O., Abd-Allah F., Akinyemi R. O., Bhattacharjee N. V., Brainin M., Cao J., Caso V., Dalton B., Davis A., Dempsey R., Duprey J., Feng W., Ford G. A., Gall S., Gandhi D., Good D. C., Hachinski V., Hacke W., Hankey G. J., Ishida M., Johnson W., Kim J., Lavados P., Lindsay P., Mahal A., Martins S., Murray C., Nguyen T. P., Norrving B., Olaiya M. T., Olalusi O. V., Pandian J., Phan H., Platz T., Ranta A., Rehman S., Roth G., Sebastian I. A., Smith A. E., Suwanwela N. C., Sylaja P. N., Thapa R., Thrift A. G., Uvere E., Vollset S. E., Yavagal D., Yaria J., Abera S. F., Akinyemi R., Dempsey R. J., Ibrahim N. M., Liu L., Ovbiagele B., Piradov M., Suwanwela N., Abanto C., Addissie A., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Akhmetzhanova Z., Akpalu A., El Alaoui-Faris M., Ameriso S. F., Andonova S., Arsovska A., Awoniyi F. E., Bakhiet M., Barboza M. A., Basri H., Bath P. M., Bereczki D., Beretta S., Berkowitz A. L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M. S., Bohara M., Bovet P., Budincevic H., Cadilhac D. A., Cerimagic D., Charway-Felli A., Chen C., Chin J. H., Christensen H., Chwojnicki K., Conforto A. B., Correia M., Mora Cuervo D. L., Czlonkowska A., D'Amelio M., Danielyan K. E., Davis S., Demarin V., Demchuk A. M., Dichgans M., Dokova K., Donnan G., Duran J. C., Ekeng G., Elkind M. S., Endres M., Fischer U., Flomin Y., Gankpe F., Gavidia M., Gaye Saavedra A., Gebreyohanns M., George M., Gierlotka M., Giroud M., Gnedovskaya E. V., Goncalves I. P., Gongora-Rivera F., Gunaratne P. S., Hamadeh R. R., Hamzat T. -H. K., Heldner M. R., Ibrahim E., Ihle-Hansen H., Jee S., Jiann-Shing J., Johnston S. C., Jovanovic D., Jurjans K., Kalani R., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Kiechl S., Kondybayeva A., Korv J., Kozera G., Kravchenko M., Krespi Y., Krishnamurthi R., Kruja J., Kutluk K., Langhorne P., Law Z. K., Lebedynets D., Lee T. -H., Leung T. W., Liebeskind D. S., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion M. J., Maia L. F., Malojcic B., Markus H. S., Marquez-Romero J. M., Medina M. T., Medukhanova S., Mehndiratta M. M., Miglane E., Mihejeva I., Mikulik R., Mirrakhimov E., Mohl S., Munakomi S., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C. H., Noubiap J. J., Novarro-Escudero N., Ocampo C., O'Donnell M., Ogun Y., Ogunniyi A., Oraby M. I., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Pereira T., Peeters A., Potpara T., Proios H., Rathore F. A., Sacco R. L., Sahathevan R., Sandset E. S., Renato Santos I., Saposnik G., Sarfo F. S., Sargento-Freitas J., Sharma M., Shaw L., Sheth K. N., Shin Y. -I., Shobhana A., Silva S. N., Tedim Cruz V., Thakur K., Thapa L. J., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tulloch-Reid M., Useche J. N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wojtyniak B., Wolfe C., Yacouba M. N., Yang J., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zagozdzon P.

Published
2023

225. INIBIÇÃO FARMACOLÓGICA DE EZRINA REDUZ O CRESCIMENTO E REGULA GENES RELACIONADOS APOPTOSE E CICLO CELULAR EM LEUCEMIA LINFOBLÁSTICA AGUDA

Author

JCL Silva, HP Vicari, K Lima, LV Costa-Lotufo, and JA Machado-Neto

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Objetivos: A leucemia linfoblástica aguda (LLA) é uma neoplasia hematológica caracterizada por uma parada no processo de diferenciação de precursores linfóides em um estágio inicial e que pode invadir medula óssea, sangue periférico e locais extramedulares. As opções terapêuticas disponíveis para a pacientes adultos ainda permanecem limitadas, e as taxas de sobrevida global em 5 anos é inferior a 45%. Um dos principais objetivos do tratamento é prevenir recidivas e diminuir a invasividade em outros órgãos. Recentemente, nosso grupo de pesquisa identificou o gene EZR, que codifica a proteína ezrina, como um marcador independente de prognóstico e alvo molecular para leucemia mieloide aguda. A ezrina é uma importante proteína associada ao citoesqueleto e que permite a transdução de sinal entre proteínas de membrana e filamentos de actina. O objetivo do presente estudo foi verificar o impacto da inibição farmacológica de ezrina sobre a viabilidade, crescimento clonal autônomo e expressão gênica em modelos celulares de LLA. Material e métodos: A linhagens celulares leucêmicas Jurkat (PTEN mutada) NALM6 (ETV6-EBF1) e REH (ETV6-RUNX1) foram tratadas com concentrações crescentes dos inibidores de ezrina, NSC305787 e NSC668394. A viabilidade celular foi avaliada pelo ensaio de MTT, o crescimento de colônias autônomas por cultivo em metilcelulose na ausência de fatores de crescimento, análises de expressão gênica foram realizadas por PCR quantitativo para a avaliação da expressão de genes relacionados ciclo celular e à apoptose. As análises estatísticas foram realizadas pelo teste ANOVA e pós-teste de Bonferroni e um valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: O tratamento com ambos os inibidores foi capaz de reduzir significativamente a viabilidade celular de células Jurkat, NALM6 e REH de forma dependente de concentração (p < 0,05). O composto NSC305787 apresentou maior potência e eficácia que o NSC668394, portanto o composto NSC305787 foi selecionado para continuidade dos estudos. Os valores de IC50 para o composto NSC305787 foram de 5.1 μM para Jurkat, 3.3 μM para NALM6 e 4.3 μM para REH no tempo de tratamento de 24 horas. O tratamento em longo prazo com NSC305787 reduziu o crescimento clonal autônomo de células Jurkat, NALM6 e REH de forma dependente de concentração (p < 0,05). Um painel de 12 genes relacionados ao ciclo celular e apoptose foi investigado por RT-PCR quantitativo. NSC305787 (1,6 μM por 24 horas), regulou negativamente CCNA2, e regula positivamente CDKN1A, BCL2L1 e BIM (p < 0,05) em células Jurkat; regulou negativamente CCNA2 e BCL2, e positivamente BCL2L1, BAX e BAD em células NALM6; regulou negativamente CCNA2 e CCNB1 e regula positivamente CDKN1A, CDKN1B, BCL2L1, MCL1 e BAX em células REH. Discussão: A regulação negativa de genes relacionados a progressão do ciclo celular (CCNA2 e CCNB1) e resposta antiapoptótica (BCL2) e regulação positiva de genes relacionados a parada de ciclo celular (CDKN1A, CDKN1B), genes pró apoptóticos (BAX) apóiam a hipótese de que NSC305787 esteja envolvido com mecanismos de indução de morte celular. Conclusão: Nossos resultados indicam que o inibidor de ezrina, NSC305787, apresenta efeitos antileucêmicos em LLA, incluindo redução da viabilidade e clonogenicidade. Apoio: CNPq, CAPES e FAPESP.

Published
2021
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226. STATHMIN 1 É ALTAMENTE EXPRESSA E CONTRIBUI PARA A CLONOGENICIDADE EM MODELOS CELULARES DE LEUCEMIA PROMIELOCÍTICA AGUDA

Author

HP Vicari, JL Coelho-Silva, DA Pereira-Martins, K Lima, JCL Silva, LV Costa-Lotufo, EM Rego, F Traina, and JA Machado-Neto

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Objetivos: Stathmin 1 (STMN1) é uma proteína desestabilizadora de microtúbulos altamente expressa em neoplasias hematológicas. A proteína de fusão PML-RARα regula positivamente a expressão e atividade de STMN1. Utilizando a coorte do IC-APL, nosso grupo de pesquisa evidenciou que STMN1 é altamente expressa em amostras de medula óssea de pacientes com leucemia promielocítica aguda (LPA). No presente estudo, a associação da expressão de STMN1 com dados genômicos de pacientes com LPA, assim como os efeitos da inibição de STMN1 ou de um agente farmacológico estabilizador de microtúbulos (paclitaxel), foram investigados em células de LPA. Materiais e métodos: Os dados de expressão de RNAm de STMN1 em doadores saudáveis e pacientes com LPA foram obtidos do AmaZonia! e do estudo GSE172057. Os dados de expressão de STMN1 nas diferentes populações de células hematopoiéticas foram obtidos do estudo GSE24759. As análises de genômica funcional foram realizadas por análise de enriquecimento de conjuntos gênicos (GSEA) e Gene Ontology. Para os estudos funcionais, linhagens celulares de LPA sensíveis (NB4) e resistentes ao ATRA (NB4-R2) foram expostas ao ATRA e/ou paclitaxel. A diferenciação granulocítica foi avaliada por marcação com CD11b e morfologia. O ciclo celular foi sincronizado por bloqueio duplo de timidina. Para o silenciamento de STMN1, as células foram transduzidas com shRNA mediado por lentivírus. A viabilidade celular foi determinada pelo ensaio de MTT, clonogenicidade pelo ensaio de formação de colônias autônomas e apoptose por marcação com anexina V/PI e citometria de fluxo. Expressões de genes e proteínas foram avaliadas por qPCR e Western blot. Resultados: A expressão de STMN1 está aumentada em amostras de pacientes com LPA (p < 0,05). A expressão diferencial de STMN1 está associada a processos de ligação a macromoléculas, sinalização mediada por receptores celulares e transdução de sinal. A GSEA identificou 23 assinaturas associadas à expressão diferencial de STMN1, entre elas, alvos de E2F, alvos de MYC, ponto de verificação G2/M, reparo de DNA, glicólise e sinalização PI3K/AKT/mTOR. STMN1 é altamente expressa em progenitores hematopoiéticos iniciais e reduz durante a diferenciação celular, incluindo subpopulações granulomonocíticas. A fosforilação de STMN1 é predominante no pool de células enriquecidas com mitose. Em células NB4 e NB4-R2, o silenciamento de STMN1 diminui o crescimento clonal autônomo (p < 0,05), mas não afeta a apoptose e a diferenciação induzidas por ATRA. As células NB4 e NB4-R2 apresentam alta sensibilidade ao paclitaxel (IC50 de 3,6 nM e 1,8 nM, respectivamente). O crescimento clonal autônomo é significativamente reduzido pelo paclitaxel (p < 0,05), o qual aumenta os níveis de marcadores de estabilidade dos microtúbulos (acetil-α-tubulina) e de dano em DNA (y-H2AX e CDKN1A). Discussão: A alta expressão de STMN1 em pacientes com LPA foi confirmada em uma coorte independente. Os dados da análise genômica indicam que a expressão de STMN1 está associada a assinaturas gênicas relacionadas à proliferação e ao metabolismo em LPA. Nossos resultados destacam a contribuição de STMN1 para clonogenicidade de células leucêmicas. Conclusão: Em resumo, nosso estudo adiciona novos insights sobre as funções da STMN1 e dinâmica de microtúbulos em LPA. Financiamento: CNPq, CAPES e FAPESP.

Published
2021
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227. The Brazilian octocoral Phyllogorgia dilatata as a source of cytotoxic compounds

Author

THAYSSA S.F. FAGUNDES, ARTHUR L. MACEDO, DHIEGO B. RIGATO, BRUNO S. DO AMARAL, PAULA CHRISTINE JIMENEZ, LETÍCIA V. COSTA-LOTUFO, RENATA F.A. PEREIRA, FÁBIO AGUIAR-ALVES, ANGÉLICA R. SOARES, THATYANA R.A. VASCONCELOS, QUEZIA B. CASS, and ALESSANDRA L. VALVERDE

Subjects
Anticancer, cytotoxic, germacrone, gorgonian, marine natural products, octocoral, Science
Abstract

Abstract The extensive marine biodiversity has proved to be a promising source of substances with biomedical potential. In this study, the cytotoxicity of the Brazilian octocoral Phyllogorgia dilatata (Gorgoniidae) was evaluated against two tumor cell lines and three bacterial strains. The methanol/dichloromethane crude extract presented no antibacterial activity up to the highest concentration tested (512 µg/mL), however it revealed a noteworthy antiproliferative effect against HCT-116 (80%) and MCF-7 (54%) cell lines at 50 μg/mL. Therefore, guided by the cytotoxic activity, a multistep chemical fractionation of the extract provided the subfraction 5 (PDPH2-5) with IC50 values of 3.18 and 17.80 μg/mL against HCT-116 and MCF-7, respectively. The LC-HRMS/MS analysis of PDPH2-5 showed ions of m/z 219.1742 and 219.1743, characterized as (E,E) and (Z,E) germacrone, after a LC-DAD-SPE/NMR analysis of the hexanic fraction and comparisons of NMR data with the literature. Previously reported assessments to the cytotoxic activity of the (E,E)-diastereoisomer disclosed higher IC50 values than that obtained for the PDPH2-5 fraction, suggesting, herein, a potentiated effect of the diastereoisomeric mixture. Such remark encourage further bioactivity studies with stereoisomer mixtures and reduce the urge for compound isolation.

Published
2021
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228. Genome-Wide Association of Proprotein Convertase Subtilisin/Kexin Type 9 Plasma Levels in the ELSA-Brasil Study

Author

Isabela Bensenor, Kallyandra Padilha, Isabella Ramos Lima, Raul Dias Santos, Gilles Lambert, Stéphane Ramin-Mangata, Marcio S Bittencourt, Alessandra C Goulart, Itamar S. Santos, Jose G Mill, Jose E Krieger, Paulo A. Lotufo, and Alexandre C. Pereira

Subjects
genetic variation, genome-wide association study, atherosclerosis, proprotein convertase subtilisin/kexin type 9, colocalization analysis, Genetics, QH426-470
Abstract

Pharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia, and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genom-wide genetic variation in a healthy sample from the general population. We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the Estudo Longitudinal de Saude do Adulto cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array, and imputation was performed using the TOPMED multi-ancestry sample panel as reference. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit. We observed two genome-wide significant loci and seven loci that reached the pre-defined value of p threshold of 1×10−6. Significant variants were near KCNA5 and KCNA1, and LINC00353. Genetic variation at the PCSK9 locus was able to explain approximately 4% of the overall interindividual variations in PCSK9 levels. Colocalization analysis using eQTL data suggested RWDD3, ATXN7L1, KCNA1, and FAM177A1 to be potential mediators of some of the observed associations. Our results suggest that PCSK9 levels may be modulated by trans genetic variation outside of the PCSK9 gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identify new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.

Published
2021
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229. O lugar dos ensaios clínicos aleatorizados na pesquisa em psicoterapia: uma crítica epistemológica

Author

Thiago Pacheco de Almeida Sampaio and Francisco Lotufo Neto

Subjects
ensaio clínico randomizado, práticas baseadas em evidências, epistemologia, pragmatismo, behaviorismo, Psychology, BF1-990
Abstract

Resumo O Ensaio Clínico Aleatorizado (ECA) é considerado o tipo de desenho metodológico com maior poder de verificação da eficácia das psicoterapias. Entretanto, especialmente a partir da segunda metade do século XX, muitas críticas direcionadas às concepções epistemológicas subjacentes às ditas “ciências duras” atingiram também, no âmbito das ciências da saúde, os estudos que adotavam esse desenho. Este artigo é uma reflexão crítica sobre algumas das objeções feitas aos ECAs, avaliando de que maneira e até que ponto estes poderiam se configurar como estratégia válida de investigação científica no contexto crítico apontado. Conclui-se que o ECA pode e deve ser utilizado - desde que em contexto crítico - por seu valor pragmático, enquanto produtor de predições e intervenções capazes de solucionar problemas clínicos, inevitavelmente definidos e estabelecidos a partir do ponto de vista particular de uma comunidade.

Published
2021
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230. The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic

Author

Fernanda C.S.G. Cruz, Luciano F. Drager, Daniel B.C. Queiróz, Gabriela A. Souza, Rodrigo P. Pedrosa, Tarcya L.G Couto Patriota, Egidio L. Dórea, Marcelo Luiz C. Vieira, Camila G. Righi, Denis Martinez, Geruza A. da Silva, Giovanio V. Silva, Andrea Pio-Abreu, Paulo A. Lotufo, Isabela M. Benseãor, Luiz A. Bortolotto, Flávio D. Fuchs, and Geraldo Lorenzi-Filho

Subjects
Obstructive Sleep Apnea, Hypertension, CPAP, Medicine (General), R5-920
Abstract

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Published
2021
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231. Morphomolecular Characterization of Serum Nanovesicles From Microbiomes Differentiates Stable and Infarcted Atherosclerotic Patients

Author

Camila Rodrigues Moreno, José Antonio Franchini Ramires, Paulo Andrade Lotufo, Alexandre Matos Soeiro, Luanda Mara da Silva Oliveira, Renata Nishiyama Ikegami, Joyce Tiyeko Kawakami, Jaqueline de Jesus Pereira, Marcia Martins Reis, and Maria de Lourdes Higuchi

Subjects
myocardial infarction, extracellular vesicles, microbiome, archaea, Mycoplasma pneumoniae, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Microbial communities are considered decisive for maintaining a healthy situation or for determining diseases. Acute myocardial infarction (AMI) is an important complication of atherosclerosis caused by the rupture of atheroma plaques containing proinflammatory cytokines, reactive oxygen species, oxidized low-density lipoproteins (oxLDL), damaged proteins, lipids, and DNA, a microenvironment compatible with a pathogenic microbial community. Previously, we found that archaeal DNA-positive infectious microvesicles (iMVs) were detected in vulnerable plaques and in the sera of Chagas disease patients with heart failure. Now, we characterize and quantify the levels of serum microbiome extracellular vesicles through their size and content using morphomolecular techniques to differentiate clinical outcomes in coronary artery disease (CAD). We detected increased numbers of large iMVs (0.8–1.34 nm) with highly negative surface charge that were positive for archaeal DNA, Mycoplasma pneumoniae antigens and MMP9 in the sera of severe AMI patients, strongly favoring our hypothesis that pathogenic archaea may play a role in the worst outcomes of atherosclerosis. The highest numbers of EVs

Published
2021
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232. Initial study of an alternative technology aimed at measuring and controlling the flow rate in air conditioning ducts

Author

Andrei Testi, Marcio Abud Marcelino, Francisco Antonio Lotufo, and Teófilo Miguel de Souza

Subjects
Mechanical engineering and machinery, TJ1-1570
Abstract

This paper states that there might have around 1000 small size business jets (until nine occupants) flying across the world equipped with flow control and regulating shut-off valves that uses hot wire anemometer devices to regulate massflow rate from the bleed airflow to supply the air-conditioning and pressurization systems. However, these valves present low reliability in the field. The purpose of this paper is to evaluate the implications of a flow control and regulating shut-off valve with a non-intrusive airflow measurer device under the perspective of fluid mechanics. The Venturi technology that is commonly used technology, given its construction simplicity, precision, and broad use in the industry, is selected to substitute the flow control and regulating shut-off valves with hot wire anemometer of the mentioned small size business jets applications. This paper has adopted a numeric simulation approach utilizing the ANSYS-CFX computational fluid dynamics software to verify both the differential pressure at the Venturi device and its correspondent mass flow rate to supply the air conditioning systems of some small size business jets, considering the mass-flow rate as requested by the FAA certification requirement (0.55 lb/min per occupant). This paper shows that a mass-flow rate control and regulating shut-off valve with a Venturi device, of 1 inch and β of 0.67, is compliant with the minimum fresh air flow requested by the FAA certification requirement to operate in some small size business jets. Besides that, the software ANSYS-CFX is also effective to support the engineering analysis of flow field characteristics inherent to the applications of internal compressible flow. The numeric simulation utilizing the ANSYS-CFX computational fluid dynamics software outlined herein can lay the basis for further research related to the design of a flow control and regulating shut-off valves with a Venturi device.

Published
2021
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233. Predicted Shifts in the Distributions of Atlantic Reef-Building Corals in the Face of Climate Change

Author

Silas C. Principe, André L. Acosta, João E. Andrade, and Tito M. C. Lotufo

Subjects
corals, niche models, habitat complexity, global warming, Anthropocene, foundation species, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

Many species drive the diversity of ecosystems by adding structural complexity to the environment. In coral reefs, stony corals act as habitat-forming species, increasing niche availability for other organisms. Some coral species play key roles as reef builders due to their abundance or morpho-functional characteristics. Thus, changes in the distributions of these species can entail cascading effects in entire ecosystems. With climate change, many coral species are experiencing shifts in their distributions, threatening the preservation of coral reefs. Here, we projected the current and future distributions of three key reef builders of the Atlantic (Mussismilia hispida, Montastraea cavernosa, and the Siderastrea complex) under three relative concentration pathway scenarios: the most optimistic, the most pessimistic and one moderate scenario (RCP2.6, 4.5, and 8.5). Our models revealed that all the above species will undergo habitat loss in the future (2100) in the most pessimistic scenario, although new areas could become suitable, including regions in the eastern Atlantic Ocean. Additionally, when considering only its actual range of occurrence, M. hispida will lose habitats under all future scenarios. Moreover, in some regions of both the Tropical Northwestern Atlantic (TNA) and the Brazilian coast, these three species could disappear, with detrimental consequences for the associated communities. We highlight the need for an urgent change of course to guarantee functional reefs in the Atlantic in the future.

Published
2021
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234. Mortalidade por COVID-19 padronizada por idade nas capitais das diferentes regiões do Brasil

Author

Gulnar Azevedo e Silva, Beatriz Cordeiro Jardim, and Paulo Andrade Lotufo

Subjects
COVID-19, Desigualdades em Saúde, Mortalidade, Medicine, Public aspects of medicine, RA1-1270
Abstract

O crescimento acentuado de casos e óbitos por COVID-19 tem levado à grande sobrecarga do sistema de saúde no Brasil, em especial em cidades como Manaus (Amazonas), Rio de Janeiro e São Paulo. A descrição do impacto da pandemia tem se baseado em números absolutos ou taxas de mortalidade brutas, não considerando o padrão de distribuição das faixas etárias nas diferentes regiões do país. Este estudo tem por objetivo comparar as taxas de mortalidade brutas por COVID-19 com as taxas padronizadas por idade nas capitais dos estados brasileiros e no Distrito Federal. As informações sobre óbito foram acessadas no Sistema de Informação de Vigilância da Gripe (SIVEP-Gripe), e os denominadores populacionais foram baseados nas estimativas disponibilizadas pelo Ministério da Saúde. Para o cálculo das taxas padronizadas por idade, utilizou-se a estrutura etária da população do Brasil estimada para 2020. Os resultados mostram que as maiores taxas brutas foram em Manaus (253,6/100 mil) e no Rio de Janeiro (253,2/100 mil). Após padronização por idade, houve aumento expressivo das taxas na Região Norte. A maior taxa ajustada foi vista em Manaus (412,5/100 mil) onde 33% de óbitos por COVID-19 ocorreram entre menores de 60 anos. A mortalidade em Manaus acima de 70 anos foi o dobro se comparada à do Rio de Janeiro e o triplo se comparada à de São Paulo. A utilização de taxas de mortalidade padronizadas por idade elimina vieses interpretativos, expondo, de forma marcante, o peso ainda maior da COVID-19 na Região Norte do país.

Published
2021
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235. Post-acute sequelae of SARS-CoV-2 infection (PASC): a protocol for a multidisciplinary prospective observational evaluation of a cohort of patients surviving hospitalisation in Sao Paulo, Brazil

Author

Paulo A Lotufo, Juliana C Ferreira, Eloisa Bonfa, Marta Imamura, Roger Chammas, Thais Mauad, Izabel Marcilio, Nelson Gouveia, Anna Sara Levin, Bruno Fukelmann Guedes, Luiz Henrique Martins Castro, Ricardo Nitrini, José Eduardo Krieger, Geraldo Filho Busatto, Adriana Ladeira de Araújo, Alberto José da Silva Duarte, Esper Georges Kallas, Fabio Rezende Pinna, Heraldo Possolo de Souza, Katia Regina da Silva, Marcio Valente Yamada Sawamura, Marilia Seelaender, Michelle Louvaes Garcia, Orestes Vicente Forlenza, Rodolfo Furlan Damiano, Vanderson Geraldo Rocha, Linamara Rizzo Batisttella, Carlos Roberto Ribeiro de Carvalho, Claudia da Costa Leite, Cristiano Gomes, Emmanuel A. Burdmann, Euripedes C. Miguel, Giovanni G. Cerri, Guilherme Fonseca, Jorge Hallak, Luis Yu, Maria Cassia J Mendes Corrêa, Marcio Mancini, Maria Elizabeth Rossi, Ricardo Ferreira Bento, Rossana Pulcinelli Francisco, Thiago Avelino-Silva, Wilson Jacob Filho, Edivaldo M Utiyama, Aluisio C Segurado, Beatriz Perondi, Anna Miethke-Morais, Amanda C Montal, Leila Harima, Solange R G Fusco, Marjorie F Silva, Marcelo C Rocha, Izabel Cristina Rios, Fabiane Yumi Ogihara Kawano, Maria Amélia de Jesus, Carolina Carmo, Clarice Tanaka, Julio F M Marchini, Maura Salaroli Oliveira, Thaís Guimarães, Carolina dos Santos Lázari, Ester Sabino, Marcello MC Magri, Tarcisio E P Barros-Filho, and Maria Cristina Peres Braido Francisco

Subjects
Medicine
Abstract

Introduction COVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity.Methods and analyses We will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1–2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6–9 months and 12–15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics.Ethics and dissemination All components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples.Trial registration number RBR-8z7v5wc; Pre-results.

Published
2021
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236. Cinema brasileiro e o ensino dos transtornos da personalidade

Author

Tabata Galindo Honorato, Maria Cristina Mazzaia, Amanda Carolina Franciscatto Avezani, and Francisco Lotufo Neto

Subjects
Transtornos da Personalidade, Filmes Cinematográficos, Filmes Educativos, Ensino, Aprendizagem, Education (General), L7-991, Medicine (General), R5-920
Abstract

Resumo: Introdução: O uso de filmes comerciais em sala de aula é uma prática comum e acessível. A prática de exibição de filmes para o ensino é definida pelo termo cinemeducation. Objetivo: O presente estudo partiu da hipótese de que o cinemeducation, como metodologia ativa, poderia contribuir para o aprendizado dos transtornos da personalidade (TP) na graduação. Foram ministradas aulas presenciais para 213 estudantes de Medicina, Enfermagem, Psicologia, Fisioterapia e Fonoaudiologia, para avaliar o conhecimento desenvolvido sobre TP. Método: O estudo é transversal e quantitativo, composto por amostras pareadas e dependentes (antes e depois). As etapas foram: 1. aplicação de instrumento avaliativo em forma de questionário (antes); 2. aula composta por exibição de cenas de filmes brasileiros e reflexão e discussão sobre elas; 3. aplicação do mesmo questionário (depois); e 4. análise estatística comparativa entre os resultados. Resultados: O método se mostrou efetivo para o processo ensino-aprendizagem, havendo melhora autorreferida no conhecimento dos estudantes após a aula (questão 1) e melhora observável ao identificarem e conceituarem os TP (questão 3). Além disso, os estudantes referiram, em média, que a estratégia contribuía para a aprendizagem, antes da aula, e mantiveram em média essa opinião, depois (questão 2). Conclusões: Alcançou-se o objetivo proposto porque se utilizou amostra estatisticamente significativa de estudantes, e os resultados confirmaram que o método é efetivo para o ensino. Além disso, a discussão evidenciou que o uso dos filmes pode contribuir para o o aprendizado, condizendo com as características de estudantes da geração atual, uma vez que valoriza o uso de tecnologias em sala de aula e permite o aprendizado crítico-reflexivo e a participação ativa dos sujeitos. As limitações do estudo se referem à escassez de filmes brasileiros contemporâneos que exemplifiquem todos os TP, não havendo cenas representativas para TP esquizotípica, dependente e esquiva. Além disso, considera-se necessário estudo comparativo entre o método tradicional de ensino dos TP e o cinemeducation, de forma a investigar a eficácia deste quando comparado às aulas tradicionais.

Published
2021
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238. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013

Author

Ng, Marie, Fleming, Tom, Robinson, Margaret, Thomson, Blake, Graetz, Nicholas, Margono, Christopher, Mullany, Erin C, Biryukov, Stan, Abbafati, Cristiana, Abera, Semaw Ferede, Abraham, Jerry P, Abu-Rmeileh, Niveen ME, Achoki, Tom, AlBuhairan, Fadia S, Alemu, Zewdie A, Alfonso, Rafael, Ali, Mohammed K, Ali, Raghib, Guzman, Nelson Alvis, Ammar, Walid, Anwari, Palwasha, Banerjee, Amitava, Barquera, Simon, Basu, Sanjay, Bennett, Derrick A, Bhutta, Zulfiqar, Blore, Jed, Cabral, Norberto, Nonato, Ismael Campos, Chang, Jung-Chen, Chowdhury, Rajiv, Courville, Karen J, Criqui, Michael H, Cundiff, David K, Dabhadkar, Kaustubh C, Dandona, Lalit, Davis, Adrian, Dayama, Anand, Dharmaratne, Samath D, Ding, Eric L, Durrani, Adnan M, Esteghamati, Alireza, Farzadfar, Farshad, Fay, Derek FJ, Feigin, Valery L, Flaxman, Abraham, Forouzanfar, Mohammad H, Goto, Atsushi, Green, Mark A, Gupta, Rajeev, Hafezi-Nejad, Nima, Hankey, Graeme J, Harewood, Heather C, Havmoeller, Rasmus, Hay, Simon, Hernandez, Lucia, Husseini, Abdullatif, Idrisov, Bulat T, Ikeda, Nayu, Islami, Farhad, Jahangir, Eiman, Jassal, Simerjot K, Jee, Sun Ha, Jeffreys, Mona, Jonas, Jost B, Kabagambe, Edmond K, Khalifa, Shams Eldin Ali Hassan, Kengne, Andre Pascal, Khader, Yousef Saleh, Khang, Young-Ho, Kim, Daniel, Kimokoti, Ruth W, Kinge, Jonas M, Kokubo, Yoshihiro, Kosen, Soewarta, Kwan, Gene, Lai, Taavi, Leinsalu, Mall, Li, Yichong, Liang, Xiaofeng, Liu, Shiwei, Logroscino, Giancarlo, Lotufo, Paulo A, Lu, Yuan, Ma, Jixiang, Mainoo, Nana Kwaku, Mensah, George A, Merriman, Tony R, Mokdad, Ali H, Moschandreas, Joanna, Naghavi, Mohsen, Naheed, Aliya, Nand, Devina, Narayan, KM Venkat, Nelson, Erica Leigh, Neuhouser, Marian L, Nisar, Muhammad Imran, Ohkubo, Takayoshi, Oti, Samuel O, and Pedroza, Andrea

Subjects
Pediatric, Prevention, Obesity, Nutrition, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Aetiology, Prevention of disease and conditions, and promotion of well-being, 2.4 Surveillance and distribution, Metabolic and endocrine, Stroke, Good Health and Well Being, Adolescent, Adult, Child, Cost of Illness, Female, Humans, Male, Models, Theoretical, Overweight, Prevalence, Regression Analysis, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundIn 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013.MethodsWe systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs).FindingsWorldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down.InterpretationBecause of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene.FundingBill & Melinda Gates Foundation.

Published
2014

239. NP3 MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics.

Author

Bazzano, Cristina F., de Felicio, Rafael, Alves, Luiz Fernando Giolo, Costa, Jonas Henrique, Ortega, Raquel, Vieira, Bruna Domingues, Morais-Urano, Raquel Peres, Furtado, Luciana Costa, Ferreira, Everton L. F., Gubiani, Juliana R., Berlinck, Roberto G. S., Costa-Lotufo, Leticia V., Telles, Guilherme P., and B. B. Trivella, Daniela

Published
2024
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240. Association between branched-chain amino acids and renal function in the ELSA-Brasil study.

Author

Calice-Silva, Viviane, Bensenor, Isabela M., Titan, Silvia M., Cavalcante, Marcos Rafael N., and Lotufo, Paulo A.

Abstract

Epidemiologic studies show high circulating Branched-chain amino acids (BCAA) are associated with excess body weight, impaired fasting glucose, insulin resistance, high blood pressure, and dyslipidemia. There is scarce data on the association between renal function and circulating levels of BCAA. Therefore, we aim to study this association in a sample of the Brazilian Longitudinal Study of Adults (ELSA-Brasil) We analyzed participants who had at the baseline BCAA: valine, isoleucine, and leucine measured through nuclear magnetic resonance. The outcomes evaluated were estimated glomerular function (eGFR - CKD-EPI without race) and 12h-albumin-creatinine ratio (ACR). In addition, we built unadjusted and adjusted multivariable linear regression models to investigate the association between the BCAA (total and individual) and eGFR and ACR. We studied 4912 participants (age 51.7(±9.0) years, 53.4% women, 59.5% White (59.5%), 32.7% hypertension, and 18.2% diabetes). The mean BCAA level was 429.15 ± 87.15. The mean eGFR was 84.95 ± 15 ml/min/1.73 m2, and the median ACR was 6.5 (1.8–4920) mg/g. Descriptive analyses comparing eGFR stratified <60 ml/min/1.73 m2 and ACR≥30 mg/g demonstrate that BCAA levels are higher in patients with eGFR<60 and ACR ≥30. Regarding eGFR, an inverse association was detected with BCAA levels when adjusted for demographic variables, and it is not maintained after adjustments for other confounders. Also, a positive association was found for ACR≥30 mg/g, and BCAA levels, and this association is not confirmed after adjustments. BCAA levels were inversely associated with eGFR and positively associated with ACR. Further studies are necessary to allow the comprehension of those associations. [ABSTRACT FROM AUTHOR]

Published
2024
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241. Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial.

Author

Borrione, Lucas, Cavendish, Beatriz A., Aparicio, Luana V. M., Luethi, Matthias S., Goerigk, Stephan, Ramos, Matheus R. F., Moran, Natasha K. S., Carneiro, Adriana M., Valiengo, Leandro, Moura, Darin O., de Souza, Juliana P., Batista, Mariana P., Aparecida da Silva, Valquiria, Klein, Izio, Suen, Paulo, Gallucci-Neto, José, Padberg, Frank, Razza, Lais B., Vanderhasselt, Marie-Anne, and Lotufo, Paulo A.

Subjects
TRANSCRANIAL direct current stimulation, PSYCHOTHERAPY, CLINICAL trials, HAMILTON Depression Inventory, BEHAVIOR therapy
Abstract

Key Points: Question: What is the efficacy of fully unsupervised home-use transcranial direct current stimulation (tDCS) combined with either a digital psychological intervention or digital placebo for the treatment of a major depressive episode? Findings: In this randomized clinical trial including 210 adults with a major depressive episode, no statistically significant differences were detected between home-use tDCS combined with either a digital psychological intervention or digital placebo vs sham in reducing depressive symptoms after 6 weeks. Meaning: The findings indicate that unsupervised home use tDCS should not be currently recommended in clinical practice. This randomized clinical trial evaluates the efficacy of home-use transcranial direct current stimulation, combined or not with a digital psychological intervention, vs sham for the treatment of major depression. Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, −0.48 to 0.58; P =.86), double active vs double sham (Cohen d, −0.20; 95% CI, −0.73 to 0.34; P =.47), and tDCS only vs double sham (Cohen d, −0.25; 95% CI, −0.76 to 0.27; P =.35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976 [ABSTRACT FROM AUTHOR]

Published
2024
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243. Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial

Author

Andre R. Brunoni, Angel Carracedo, Olalla M. Amigo, Ana L. Pellicer, Leda Talib, Andre F. Carvalho, Paulo A. Lotufo, Isabela M. Benseñor, Wagner Gattaz, and Carolina Cappi

Subjects
Major depressive disorder, non-invasive brain stimulation, single-nucleotide polymorphism, selective serotonin reuptake inhibitors, randomized clinical trial, Psychiatry, RC435-571
Abstract

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.

Published
2019
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244. Prevalence and correlates of depression, anxiety, and stress in medical residents of a Brazilian academic health system

Author

Paula Lage Pasqualucci, Luciana Luccas Mendes Damaso, Arthur Hirschfeld Danila, Daniel Fatori, Francisco Lotufo Neto, and Vera Hermina Kalika Koch

Subjects
Medical residents, Mental health, Burnout syndrome, Quality of life, Special aspects of education, LC8-6691, Medicine
Abstract

Abstract Background Several studies correlate medical residency with the occurrence of mental health disorders, Burnout Syndrome and quality of life impairment. It has been demonstrated that mental health disorders increase medical errors and lead to less effective patient care. Considering such context, this study aimed to evaluate the prevalence of anxiety, depression, stress and to identify its correlates with Burnout Syndrome and quality of life in a sample of medical residents and fellow physicians of the largest Brazilian academic health system. Methods In 2017, 1648 participants were voluntarily and anonymously surveyed online about demographic characteristics, Burnout Syndrome, mental symptoms, and quality of life measured by validated questionnaires. Responses were captured through REDCap platform and multivariate statistical analyses were performed with STATA 15. Results A total of 606 (36.8%) residents/fellows physicians completed the survey. Depression symptoms were present in 19%, anxiety symptoms in 16% and stress symptoms in 17.7% of the sample. Burnout Syndrome was present in 63% of the sample. Multivariate analysis showed a statistical significant positive correlation between Burnout Syndrome and depression, anxiety and stress symptoms and a negative correlation between mental symptoms and quality of life scores. Conclusions Mental health symptoms prevalence in this study is similar to other studies and their occurrence is positively correlated with Burnout Syndrome among medical residents/fellow physicians of the largest Brazilian academic health system. These results are relevant and must be confirmed by multicentric longitudinal studies. This study reinforces the importance of debating interventions to improve mental health among doctors in training.

Published
2019
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245. Pragmatic Validation of Home Portable Sleep Monitor for diagnosing Obstructive Sleep Apnea in a non-referred population: The ELSA-Brasil study

Author

Aline N. Aielo, Ronaldo B. Santos, Wagner A. Silva, Barbara K. Parise, Silvana P. Souza, Lorenna F. Cunha, Soraya Giatti, Paulo A. Lotufo, Isabela M. Bensenor, and Luciano F. Drager

Subjects
sleep apnea, diagnosis, polysomnography, wrist, Psychology, BF1-990, Consciousness. Cognition, BF309-499
Abstract

Objective: Polygraphy (PG) is an attractive alternative for diagnosing obstructive sleep apnea (OSA) in patients with high pre-test probability. However, several patients may not present typical symptoms. In this scenario, it is unclear the performance of PG for diagnosing OSA in nonreferred populations to sleep laboratories. Methods: Data from participants of the ELSA-Brasil cohort were used for this analysis. We performed an overnight home PG (Embletta GoldTM) synchronized with a wrist actigraphy (Actiwatch model 2TM). The validation strategy comprised three scorings from each participant: 1) Original scoring (PG): Routine scoring using data from the exclamation button mark to define “analysis start” and “analysis stop”; 2) Scoring using actigraphy data (PG+actigraphy): total sleep time defined by the actigraphy data; 3) Scoring using diaries (PG+diary): “analysis start” and “analysis stop” based on the diaries. Bland-Altman plots were generated to assess the agreements (Kappa) between each scoring strategy. Results: A total of 300 participants were included in the final analysis (45% males, mean age: 48±8 years). The frequency of OSA using the PG score was 27.3%. Despite small differences in the OSA severity index, we obtained a high concordance of AHI comparing the PG vs. PG+actigraphy (Kappa: 0.95) as well as PG+diary vs. PG+actigraphy (Kappa: 0.96). No significant changes in the OSA classification (mild, moderate and severe) were observed in the 3 protocols. Conclusion: Using a pragmatic approach to address OSA at home, our results suggest that PG is a useful tool for OSA diagnosis even in subjects not referred to sleep studies.

Published
2019
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246. Low serum levels of CCL2 are associated with worse prognosis in patients with Acute Coronary Syndrome: 2-year survival analysis

Author

Paola Caroline Lacerda Leocádio, Penélope Lacrísio dos Reis Menta, Melissa Tainan Silva Dias, Júlia Rodrigues Fraga, Alessandra Carvalho Goulart, Itamar Souza Santos, Paulo Andrade Lotufo, Isabela Martins Bensenor, and Jacqueline Isaura Alvarez-Leite

Subjects
Acute Coronary Syndrome, CCL2, Coronary Artery Disease, Myocardial infarction, Prognosis, Therapeutics. Pharmacology, RM1-950
Abstract

Inflammation is very important in Acute Coronary Syndrome (ACS) as well as in cardiac remodeling after an acute myocardial infarction (MI). Our study examined the prognostic value of Chemokine (C-C motif) ligand 2 (CCL2) in patients with ACS in the ERICO (Strategy of Registry of Acute Coronary Syndrome) study. We evaluated serum samples from 803 patients. The prognostic value of CCL2 was evaluated at the 2-year follow-up, according to cutoff points established by the median. Kaplan-Meier curves and Cox regression were used for analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction or new non-fatal MI. There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. CCL2 levels below the median (≤100.9 pg/mL) were associated with increased risk of MI death or new non-fatal MI, even after model adjustment. Low serum levels of CCL2 shows a significant association with fatal or new non-fatal MI.

Published
2019
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247. Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs

Author

Rodrigo dos A. Miguel, Amanda S. Hirata, Paula C. Jimenez, Luciana B. Lopes, and Leticia V. Costa-Lotufo

Subjects
anticancer drugs, natural products, drug delivery, nanotechnology, paclitaxel, doxorubicin, Pharmacy and materia medica, RS1-441
Abstract

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to modification of pharmacokinetic properties and tissue targeting. In addition, nanotechnology-based drugs can contribute to dose modulation, reversion of multidrug resistance, and protection from degradation and early clearance; can influence the mechanism of action; and can enable drug administration by alternative routes and co-encapsulation of multiple active agents for combined chemotherapy. In this review, we discuss the contribution of nanotechnology as an enabling technology taking the clinical use of DOX and PTX as examples. We also present other nanoformulations approved for clinical practice containing different anticancer natural-product-derived drugs.

Published
2022
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248. The Relationship between COVID-19 and Hypothalamic–Pituitary–Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess—The CAPISCO International Expert Panel

Author

Mojca Jensterle, Rok Herman, Andrej Janež, Wael Al Mahmeed, Khalid Al-Rasadi, Kamila Al-Alawi, Maciej Banach, Yajnavalka Banerjee, Antonio Ceriello, Mustafa Cesur, Francesco Cosentino, Massimo Galia, Su-Yen Goh, Sanjay Kalra, Peter Kempler, Nader Lessan, Paulo Lotufo, Nikolaos Papanas, Ali A. Rizvi, Raul D. Santos, Anca P. Stoian, Peter P. Toth, Vijay Viswanathan, and Manfredi Rizzo

Subjects
SARS-CoV-2, glucocorticoids, hypothalamic–pituitary–adrenal axis, hypercortisolism, adrenal insufficiency, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

Published
2022
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249. Marine Streptomyces sp. Isolated From the Brazilian Endemic Tunicate Euherdmania sp. Produces Dihydroeponemycin and Analogs With Potent Antiglioma Activity

Author

Luciana C. Furtado, Anelize Bauermeister, Rafael de Felicio, Raquel Ortega, Francisco das Chagas L. Pinto, João Agostinho Machado-Neto, Daniela B. B. Trivella, Otilia D. L. Pessoa, Diego V. Wilke, Norberto P. Lopes, Paula C. Jimenez, and Leticia V. Costa-Lotufo

Subjects
marine natural products, cytotoxicity, proteasome inhibitors, epoxyketones, ER-stress response, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

Marine natural products have emerged as an important source for drug development, notably in the field of anticancer therapy. Still, the limited effectiveness of current therapies for central nervous system tumors indicates the need to identify new therapeutic targets and also novel pharmacological agents. In this context, proteasome inhibitors are appearing as a promising new treatment for these diseases. Herein, cytotoxic extracts produced by four marine bacteria recovered from the Brazilian endemic ascidian Euherdmania sp. were screened to evaluate their potential as proteasome inhibitors. The extract from marine Streptomyces sp. BRA-346 was selected for further investigation due to the potent proteasome inhibitory activity it displayed. Bioassay-guided fractionation led to an enriched fraction (proteasome inhibition IC50 = 45 ng/mL), in which the presence of dihydroeponemycin (DHE), known for its proteasome inhibitory effect, and related compounds were annotated by mass spectrometry and further confirmed by comparison with DHE standard. Both DHE and the epoxyketone-containing fraction were evaluated in glioma cell lines, displaying high cytotoxicity in HOG and T98G cells (GI50 of 1.6 and 1.7 ng/mL for DHE, and 17.6 and 28.2 ng/mL for the BRA-346 fraction, respectively). Additional studies showed that the epoxyketone-containing fraction (at GI50 levels) led to an accumulation of ubiquitinated proteins and up-regulation of genes related to ER-stress response, suggesting treated cells are under proteasome inhibition. DHE induced similar effects in treated cells but at concentrations 25 times its GI50, suggesting that the other epoxyketone compounds in the bacteria extract derived fraction may contribute to enhance proteasome inhibition and further cellular effects in glioma cells. These findings revealed the molecular pathways modulated by this class of compounds in glioma cells and, moreover, reinforced the potential of this marine bacteria in producing a cocktail of structurally-related compounds that affect the viability of glioma cells.

Published
2021
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250. Generation of 6 lines of human pluripotent stem cells from hypertensive patients and 3 lines of human pluripotent stem cell from normotensive patients

Author

Raquel Sarafian, Mariana Morato-Marques, Juliana Borsoi, Fabiano Tófoli-Araújo, Mara Pinheiro, Yordanka Medina-Armenteros, Paulo A. Lotufo, Isabela M. Bensenor, and Lygia V. Pereira

Subjects
Biology (General), QH301-705.5
Abstract

Hypertension is a complex multifactorial disease characterized by a chronic increase of arterial pressure. Ninety percent of the cases are idiopathic and thus classified as essential hypertension. Uncontrolled arterial pressure has devasting consequences including cardiac insufficiency, stroke, dementia, chronic renal disease, ischemic heart disease and death. The hiPSC lines described here from six hypertensive patients and three controls were characterized according to established criteria and were shown to maintain pluripotency, differentiation into the three germ layers and genomic integrity. These cell lines can contribute to the understanding of the molecular mechanisms involved in hypertension in different cell types.

Published
2021
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