Enantioselective Synthesis of Dihydrobenzofurans, Dihydrobenzosulfones, and Dihydroindoles by Merging One-pot Intramolecular Heck-Matsuda Reactions from Anilines with Redox-Relay Process.

A one-pot tandem process was developed aiming at the concise and expeditious enantioselective synthesis of dihydrobenzofuran, dihydrobenzosulfone, and dihydroindole scaffolds under mild, and open-flask conditions. This process combines the in situ generation of aryldiazonium salt directly from the anilines in methanol telescoped to an intramolecular Heck-Matsuda reaction linked to a redox relay process to provide the final products as the dimethyl acetals. These Heck products were smoothly converted into the corresponding primary alcohols or esters. The robustness and the efficiency of the protocol are demonstrated by the synthesis of 24 enantioenriched dihydrobenzofurans, dihydrobenzosulfones, and dihydroindoles in overall yields up to 78 % in enantiomeric ratios up to 99 : 1 by a sequential 5-step protocol.

Artéria subclávia direita aberrante: relato de caso e revisão de literatura / Aberrant right subclavian artery: case report and literature review

Resumo A artéria subclávia direita aberrante, também conhecida como artéria lusória, é a anomalia do arco aórtico mais comum, ocorrendo entre 0,5 e 1% da população. Possui prevalência em mulheres e normalmente está associada a outras variações anatômicas, como o nervo laríngeo não recorrente, presente em 86,7% dos casos. Em sua maioria, a artéria subclávia direita aberrante não apresenta sintomas. Descrevemos essa alteração em uma paciente de 82 anos, hipertensa e assintomática, que havia sido submetida a uma angiotomografia toracoabdominal para a avaliação de uma dissecção crônica tipo III (DeBakey) associada à dilatação de aorta descendente. No achado, a artéria subclávia direita aberrante apresentava percurso retroesofágico associado a um divertículo de Kommerell. Devido à raridade, realizamos revisão bibliográfica integrativa das bases de dados MEDLINE, UpToDate, LILACS, SciELO e Portal CAPES dos últimos 6 anos e discutimos as alterações anatômicas mais frequentes, a sintomatologia e as condutas terapêuticas adotadas.

Abstract The aberrant right subclavian artery, also known as the arteria lusoria, is the most common aortic arch anomaly, occurring in 0.5 to 1% of the population. There is a higher prevalence in women and it is usually associated with other anatomical variations, such as the non-recurrent laryngeal nerve, present in 86.7% of cases. In the majority of cases, the aberrant right subclavian artery causes no symptoms. We describe this anomaly in an 82-year-old, hypertensive, and asymptomatic patient who had undergone a thoracoabdominal angiography to investigate a chronic DeBakey type III aortic dissection with dilation of the descending aorta. The aberrant right subclavian artery followed a retroesophageal course and was associated with a Kommerell diverticulum. In view of its rarity, we conducted an integrative bibliographic review of literature from the last 6 years indexed on the Medline, UpToDate, Lilacs, Scielo, and Portal Capes databases and discuss the most frequent anatomical changes, symptomatology, and therapeutic management adopted.

A review on muscle activation behaviour during gait in shallow water and deep-water running and surface electromyography procedures.

BACKGROUND: Surface electromyography (sEMG) can provide information on muscle activation patterns during gait. OBJECTIVES: To characterize electromyographic activity during gait in shallow water and during deep-water running compare to on land and to review and analyse underwater surface-electromyographic (sEMG) procedures. SEARCH METHODS: Eight databases (MEDLINE, EMBASE, WEB OF SCIENCE, SPORT Discus, CINAHL, SCOPUS, SCIELO, and LILACS) were searched from their inception to the December of 2019. SELECTION CRITERIA: The selected studies had to be related to electromyographic analysis of gait in an aquatic environment. DATA COLLECTION AND ANALYSIS: The studies that met the inclusion criteria were reviewed by two independent reviewers and divided into four groups. RESULTS: Ten studies met the inclusion criteria. Lower muscle activation was found with treadmill water walking compared to treadmill land walking. With deep-water running, the leg muscles (tibialis anterior and gastrocnemius lateralis) have lower muscle activation when compared to on land running, but the trunk and thigh muscles have higher activation. CONCLUSION: If gait is performed on an aquatic treadmill, the muscles assessed had lower muscle activation when compared to land. During deep-water running activities, lower activation of the distal leg muscles and a higher activation thigh muscles were found when compared to on land. Studies did not follow standard processes in sEMG procedures.

Picraviane A and B: Nortriterpenes with limonoid-like skeletons containing a heptanolide E-ring system from Picramnia glazioviana.

Two highly oxygenated nortriterpenes, picraviane A and B, were isolated from the ethanolic extract of Picramnia glazioviana Engl. The structures were determined by analysis of HRMS and 2D NMR spectroscopic data. Single-crystal X-ray diffraction data was also obtained for picraviane B. The absolute configuration of both compounds were assigned by comparison of experimental and calculated vibrational and electronic circular dichroism spectroscopy, respectively. Picraviane A showed a moderate cytotoxic activity against the triple negative MDA-MB-231 breast cancer cell line. These compounds represent an undescribed class of natural products with limonoid-like skeletons containing a heptanolide as the E-ring.

Postural Sway, Balance Confidence, and Fear of Falling in Women With Knee Osteoarthritis in Comparison to Matched Controls.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative disease that commonly affects the knee joints. Individuals older than 65 years of age with knee OA have a greater risk of falls. However, there has been limited examination of the parameters of postural sway (increased time, speed, and postural sway area [center of pressure{CoP}]), and OA of the knee. OBJECTIVES: The primary objective of this study was to determine whether the CoP variables discriminate between patients with knee OA and matched healthy volunteers, and to correlate the CoP variables with the Activities-Specific Balance Confidence Scale (ABC) and Falls Self-Efficacy Scale (FES). The secondary objective was to compare the CoP of older women with OA with a control group in bipedal support condition with eyes opened and closed. DESIGN: Cross-sectional study. SETTING: University Biomechanics Laboratory. PARTICIPANTS: A total of 22 participants were divided into the following 2 groups of 11 participants each: an OA group (mean = 68 years, standard deviation = 7.4 years) and a control group (mean = 66 years, standard deviation = 4.4 years). METHODS: Static postural balance was measured by a portable force platform. Data were collected in both visual conditions (eyes open and closed), in random order. Three attempts of 30 seconds were allowed for each participant on the force platform, with a 1-minute interval between attempts. MAIN OUTCOME MEASURE: Variables were the CoP total displacement of sway (TDS, in centimeters), anteroposterior amplitude displacement (APAD, in centimeters), medial-lateral amplitude displacement (MLAD, in centimeters), total mean velocity (TMV, in centimeters per second), and dispersion of the center of pressure (AREA, in centimeters squared). RESULTS: The postural sway analysis found statistically significant differences in the eyes open condition for the TDS (P = .020), APAD (P = .042), TMV (P = .010), and AREA (P = .045). In the discriminant analysis, none of the CoP variables were able to classify the groups (P = .15). The correlation analysis showed that only the AREA with eyes closed was associated with the ABC Scale (rho = -0.42). CONCLUSIONS: Women with knee OA had greater postural sway when compared with a control group for the eyes open condition. CoP variables could not discriminate between the groups. The AREA was negatively correlated with the ABC Scale, when the eyes were closed. LEVEL OF EVIDENCE: III.

Isokinetic evaluation of knee muscles in soccer players: discriminant analysis / Avaliação isocinética dos músculos do joelho em jogadores de futebol: análise discriminante / Evaluación isocinética de los músculos de la rodilla en jugadores de fútbol: análisis discriminante

ABSTRACTIntroduction:Muscle activity in soccer players can be measured by isokinetic dynamometer, which is a reliable tool for assessing human performance.Objectives:To perform isokinetic analyses and to determine which variables differentiate the under-17 (U17) soccer category from the professional (PRO).Methods:Thirty four players were assessed (n=17 for each category). The isokinetic variables used for the knee extension-flexion analysis were: peak torque (Nm), total work (J), average power (W), angle of peak torque (deg.), agonist/ antagonist ratio (%), measured for three velocities (60°/s, 120°/s and 300°/s), with each series containing five repetitions. Three Wilks' Lambda discriminant analyses were performed, to identify which variables were more significant for the definition of each of the categories.Results:The discriminative variables at 60°/s in the PRO category were: extension peak torque, flexion total work, extension average power and agonist/antagonist ratio; and for the U17s were: extension total work, flexion peak torque and flexion average power. At 120°/s for the PRO category the discriminant variables were: flexion peak torque and extension average power; for the U17s they were: extension total work and flexion average power. Finally at 300°/s, the variables found in the PRO and U17 categories respectively were: extension average power and extension total work.Conclusion:Isokinetic variables for flexion and extension knee muscles were able to significantly discriminate between PRO and U17 soccer players.

RESUMOIntrodução:A atividade muscular em jogadores de futebol pode ser medida por meio do dinamômetro isocinético, que é um instrumento confiável para avaliação do desempenho humano.Objetivos:Conduzir análises isocinéticas e discriminar quais variáveis diferenciam a categoria sub-17 (S17) da profissional (PRO).Métodos:Trinta e quatro jogadores de futebol (n=17 para cada categoria) foram avaliados. As variáveis isocinéticas utilizadas para a análise de extensão-flexão do joelho foram: pico de torque (Nm), trabalho total (J), potência média (W), ângulo de pico de torque (graus), razão agonista/antagonista (%), testadas em três velocidades (60°/s, 120°/s e 300°/s), com cada série contendo cinco repetições. Três análises discriminantes foram feitas usando o método Wilk's Lambda para identificar quais variáveis fariam uma discriminação significativa entre as duas categorias.Resultados:As variáveis discriminantes a 60°/s na categoria PRO foram: pico de torque extensores, trabalho total flexores, potência média de extensores e razão agonista/antagonista; e para os S17 foram: trabalho total de extensores, pico de torque de flexores e potência média de flexores. A 120°/s para a categoria PRO as variáveis discriminantes foram: pico de torque de flexores e potência média de extensores; para os S17 foram: trabalho total de extensores e potência média de flexores. A 300°/s, as variáveis encontradas para as categorias PRO e S17 foram, respectivamente: potência média de extensores e trabalho total de extensores.Conclusão:As variáveis isocinéticas para os músculos do joelho flexores e extensores foram capazes de fazer uma discriminação significativa entre jogadores de futebol PRO e S17.

RESUMENIntroducción:La actividad muscular en jugadores de fútbol puede ser medida por medio del dinamómetro isocinético, que es un instrumento confiable para evaluación del desempeño humano.Objetivos:Conducir análisis isocinéticos y discriminar qué variables diferencian la categoría sub-17 (S17) de la profesional (PRO).Métodos:Fueron evaluados treinta y cuatro jugadores de fútbol (n=17 para cada categoría). Las variables isocinéticas utilizadas para el análisis de extensión-flexión de la rodilla fueron: pico de torque (Nm), trabajo total (J), potencia media (W), ángulo de pico de torque (grados), razón agonista/antagonista (%), probadas en tres velocidades (60°/s, 120°/s y 300°/s), con cada serie conteniendo cinco repeticiones. Fueron realizados tres análisis discriminantes usando el método Wilk's Lambda para identificar qué variables harían una discriminación significativa entre las dos categorías.Resultados:Las variables discriminantes a 60°/s en la categoría PRO fueron: pico de torque extensores, trabajo total flexores, potencia media de extensores y razón agonista/antagonista; y para los S17 fueron: trabajo total de extensores, pico de torque de flexores y potencia media de flexores. A 120°/s para la categoría PRO las variables discriminantes fueron: pico de torque de flexores y potencia media de extensores; para los S17 fueron: trabajo total de extensores y potencia media de flexores. A 300°/s, las variables encontradas para las categorías PRO y S17 fueron, respectivamente: potencia media de extensores y trabajo total de extensores.Conclusión:Las variables isocinéticas para los músculos de la rodilla flexores y extensores fueron capaces de hacer una discriminación significativa entre jugadores de fútbol PRO y S17.

Low agreement between the fitnessgram criterion references for adolescents / Baixa concordância entre os critérios de referência da fitnessgram para adolescentes

OBJECTIVE: To analyze the association and agreement of fitnessgram reference criteria (RC) for cardiorespiratory fitness, body mass index (BMI) and strength in youth. METHODS: The study included 781 youth, 386 females, aged 10 to 18 years of Londrina-PR. It were performed cardiorespiratory fitness and muscular strength tests and was calculated body mass index. The association between the tests was analyzed using Poisson regression to obtain prevalence ratio (PR) and confidence intervals of 95%, while agreement of the reference criteria was tested by Kappa index. RESULTS: Significant associations were found between cardiorespiratory fitness and BMI (PR=1,49, 1,27-1,75), muscle strength and BMI (PR=1,55, 1,17-2,08), cardiorespiratory fitness and muscle strength (PR=1,81, 1,47-2,24). The agreement between reference criteria ranged from weak to fair, 48.8% (k=0.05, p=0.10) for cardiorespiratory fitness and BMI, 52.9% (k=0.09, p=0.001) for muscle strength and BMI and 38.4% (k=0.22, p<0.001) for cardiorespiratory fitness and muscle strength. CONCLUSIONS: Although RC for cardiorespiratory fitness, muscle strength and BMI are associated, the agreement between them ranged from weak to fair. To evaluate health related physical fitness it is suggest the execution of all tests, since each test has specific characteristics.

OBJETIVO: Analisar a associação e a concordância dos critérios de referência (CR) da fitnessgram para aptidão a cardiorrespiratória, índice de massa corporal (IMC) e força em jovens. MÉTODOS: Participaram do estudo 781 jovens, 386 do sexo feminino, entre 10 a 18 anos de Londrina (PR). Foram aplicados testes de aptidão cardiorrespiratória e força muscular e foi calculado o IMC. A associação entre os testes foi analisada por meio da regressão de Poisson para se obter a razão de prevalência (RP) e os respectivos intervalos de confiança de 95%, enquanto que a concordância dos critérios foi feita com o índice Kappa. RESULTADOS: Foram encontradas associações significativas entre a aptidão cardiorrespiratória e IMC (RP=1,49, 1,27-1,75), força muscular e IMC (RP=1,55, 1,17-2,08), aptidão cardiorrespiratória e força muscular (RP=1,81, 1,47-2,24). A concordância entre o atendimento dos CR variou de fraca a razoável, de 48,8% (k=0,05; p=0,10) para aptidão cardiorrespiratória e IMC, 52,9% (k=0,09; p=0,001) para a força muscular e IMC e 38,4% (k=0,22; p<0,001) para a aptidão cardiorrespiratória e força muscular. CONCLUSÕES: Apesar de os CR para a aptidão cardiorrespiratória, IMC e força muscular estarem associados, a concordância encontrada entre eles variou de fraca a razoável. Para avaliar a aptidão física relacionada à saúde recomenda-se a aplicação de todos os testes, uma vez que cada teste tem características específicas.

Genotoxic effects of the antimalarial drug lumefantrine in human lymphocytes in vitro and computational prediction of the mechanism associated with its interaction with DNA.

Lumefantrine (LF) is an aryl-amino alcohol antimalarial drug used in artemisinin-based combination therapies against malaria worldwide. In this study, we investigated the genotoxic effects of LF in human lymphocytes in vitro, and the potential noncovalent interaction of LF with DNA using a 3D DNA-docking model. The number of DNA breaks and the frequency of nuclear buds (NBUDS) was significantly increased (P < 0.01 and P < 0. 05, respectively) at LF concentrations of 60, 80, and 100 µg/mL (LF60, LF80, and LF100, respectively). Frequency (‰) of micronuclei (MN) formation also increased after LF treatments. However, this was only significant for LF100 (P = 0.01) and LF80 (P = 0.001). LF did not affect the frequency of nucleoplasmic bridges (NPBs) (P = 0.12) or the nuclear division index (NDI) (P = 0.32). Computational analysis suggests that LF may interact noncovalently with DNA via the DNA minor groove surface with a predicted binding affinity energy of -7.2 kcal/mol and showing a favorable shape complementary to this groove. Our results suggest that LF has clastogenic effects in human lymphocytes in vitro due to noncovalent interaction with the minor groove of DNA.

[Low agreement between the fitnessgram criterion references for adolescents]. / Baixa concordância entre os critérios de referência da fitnessgram para adolescentes.

OBJECTIVE: To analyze the association and agreement of fitnessgram reference criteria (RC) for cardiorespiratory fitness, body mass index (BMI) and strength in youth. METHODS: The study included 781 youth, 386 females, aged 10 to 18 years of Londrina-PR. It were performed cardiorespiratory fitness and muscular strength tests and was calculated body mass index. The association between the tests was analyzed using Poisson regression to obtain prevalence ratio (PR) and confidence intervals of 95%, while agreement of the reference criteria was tested by Kappa index. RESULTS: Significant associations were found between cardiorespiratory fitness and BMI (PR=1.49, 1.27-1.75), muscle strength and BMI (PR=1.55, 1.17-2.08), cardiorespiratory fitness and muscle strength (PR=1.81, 1.47-2.24). The agreement between reference criteria ranged from weak to fair, 48.8% (k=0.05, p=0.10) for cardiorespiratory fitness and BMI, 52.9% (k=0.09, p=0.001) for muscle strength and BMI and 38.4% (k=0.22, p<0.001) for cardiorespiratory fitness and muscle strength. CONCLUSIONS: Although RC for cardiorespiratory fitness, muscle strength and BMI are associated, the agreement between them ranged from weak to fair. To evaluate health related physical fitness it is suggest the execution of all tests, since each test has specific characteristics.

Comparison of the electrical activity in upper trapezius and wrist extensor muscles during two typewriting conditions / Comparação da atividade elétrica dos músculos trapézio superior e extensores do punho em duas condições de digitação

Introduction The proper use of the position of the arm and wrist while typing may reduce muscle overload and prevent musculoskeletal disorders.Objective To evaluate the electromyographic activity of upper trapezius and wrist extensor muscles during two typewriting conditions.Materials and methods : Six healthy females (Xage = 42 years,SD= 10), (Xheight = 1.65m, SD = 0.05) and (Xweight = 71kg, SD = 16) participated in this study. The task was performed with a newly developed arm support and without the support. A perceived exertion scale was used with all subjects. An ANOVA with repeated measures was used to verify differences in perceived exertion and root mean square (RMS).Results There were no statistically significant differences for the RMS between the typewriting tasks. The condition without arm support presented a significantly greater mean velocity and amount of words typed (P= 0.02; P= 0.03) and there was a significant difference in perceived exertion during the condition without arm support (P= 0.03). Electromyographic activity did not present differences.Conclusion The muscle electrical activity was not altered regardless the arm support and occurred the improvement of the perceived exertion after 10 minutes of typing without support. Long-term studies are needed.

Introdução O uso adequado da posição do braço e do punho durante a digitação pode reduzir a sobrecarga muscular e prevenir doenças musculoesqueléticas.Objetivo Avaliar a atividade eletromiográfica dos músculos trapézio superior e extensores do punho durante duas condições de digitação.Materiais e métodos Seis mulheres sadias (X idade = 42 anos, DP = 10), (Xaltura = 1,65m, DP = 0,05) e (Xmassa = 71 kg, DP = 16) participaram deste estudo. A tarefa foi realizada com e sem um apoio de braço. Uma escala de percepção de esforço foi aplicada para todos participantes. ANOVA de medidas repetidas foi utilizada para verificar diferenças na percepção de esforço e root mean square (RMS) para a atividade eletromiográfica.Resultados Não houve diferença estatisticamente significante para o RMS entre as tarefas de digitação. A condição sem apoio de braço apresentou maior média de velocidade e quantidade de palavras digitadas (P = 0,02; P = 0,03) e houve uma diferença significante na percepção de esforço durante a condição sem apoio de braço (P = 0,03). A atividade eletromiográfica não apresentou diferença.Conclusão A atividade elétrica muscular não se alterou independente do apoio e ocorreu a melhora do esforço percebido após 10 minutos de digitação sem apoio. Estudos em longo prazo são necessários.

Clinical oxidative stress during leprosy multidrug therapy: impact of dapsone oxidation.

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.

Simultaneous infection of human host with genetically distinct isolates of Paracoccidioides brasiliensis.

This study is the first report on genetic differences between isolates of Paracoccidioides brasiliensis from a single patient. We describe a simultaneous infection with genetically distinct isolates of P. brasiliensis in a patient with chronic paracoccidioidomycosis. The clinical isolates were obtained from lesions in different anatomical sites and were characterised by random amplified polymorphic DNA (RAPD) analysis. The RAPD technique can be helpful for distinguishing between clinical isolates. Different random primers were used to characterise these clinical isolates. The RAPD patterns allowed for differentiation between isolates and the construction of a phenetic tree, which showed more than 28% genetic variability in this fungal species, opening new possibilities for clinical studies of P. brasiliensis. Based on these results and preliminary clinical findings, we suggest that different genotypes of P. brasiliensis might infect the same patient, inducing the active form of the disease.

Simultaneous infection of human host with genetically distinct isolates of Paracoccidioides brasiliensis

This study is the first report on genetic differences between isolates of Paracoccidioides brasiliensis from a single patient. We describe a simultaneous infection with genetically distinct isolates of P. brasiliensis in a patient with chronic paracoccidioidomycosis. The clinical isolates were obtained from lesions in different anatomical sites and were characterised by random amplified polymorphic DNA (RAPD) analysis. The RAPD technique can be helpful for distinguishing between clinical isolates. Different random primers were used to characterise these clinical isolates. The RAPD patterns allowed for differentiation between isolates and the construction of a phenetic tree, which showed more than 28 percent genetic variability in this fungal species, opening new possibilities for clinical studies of P. brasiliensis. Based on these results and preliminary clinical findings, we suggest that different genotypes of P. brasiliensis might infect the same patient, inducing the active form of the disease.

In vitro trypanocidal activity of phenolic derivatives from Peperomia obtusifolia.

The trypanocidal activity of crude extracts and fractions from the leaves and stems of Peperomia obtusifolia (Piperaceae) was evaluated in vitro against the epimastigote forms of Trypanosoma cruzi. Bioactivity-guided fractionation of the most active extracts afforded seven known compounds, including three chromanes, two furofuran lignans and two flavone C-diglycosides. The most active compounds were the chromanes peperobtusin A and 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(2''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2 H-1-benzopyran-6-carboxylic acid, with IC (50) values of 3.1 microM (almost three times more active than the positive control benznidazole, IC (50) 10.4 microM) and 27.0 microM, respectively. Cytotoxicity assays using peritoneal murine macrophages indicated that the chromanes were not toxic at the level of the IC (50) for trypanocidal activity. This is the first report on the trypanocidal activity besides unspecific cytotoxicity of chromanes from Peperomia species. Additionally it represents the first time isolation of 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(2''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2 H-1-benzopyran-6-carboxylic acid from P. obtusifolia.