Convalescent plasma for COVID-19 in hospitalised patients : an open-label, randomised clinical trial

Background: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients. Methods: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. Results: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48–68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8–12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference −3.7%, 95% CI −18.8–11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups. Conclusions: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone

Tratamentos físico-químicos de bagaço de cana para produção de etanol por meio de hidrólise enzimática

O material lignocelulósico do qual o bagaço é formado contém principalmente açúcares polimerizados na forma de celulose e hemiceluloses, e compostos fenólicos polimerizados na forma de lignina. Tais polímeros podem ser hidrolisados via química e/ou enzimática, dando origem a, entre outros compostos, açúcares fermentescíveis. O objetivo desse trabalho foi investigar alguns tratamentos físico-químicos aplicados ao bagaço de cana de açúcar que favoreçam o aumento da liberação de açúcares fermentescíveis por hidrólise enzimática, com a mínima produção possível de compostos inibidores da fermentação alcoólica. Diferentes condições de pré-tratamento foram testadas, como utilização de H2SO4 ou NaOH em diferentes concentrações, concomitantemente com a utilização de tratamentos combinados de ozônio, ultrassom e micro-ondas. Os resultados mostraram que tais processos promoveram certa desestruturação do complexo lignocelulósico da parede celular do bagaço, a qual foi relacionada com a concentração de compostos fenólicos e açúcares redutores. O bagaço pré-tratado foi então submetido à ação de enzimas celulolíticas e o teor de açúcares redutores totais formados foi analisado. As condições nas quais maiores quantidades destes açúcares foram liberados foram: H2SO4 0,1 M, irradiado por ultrassom durante 5 minutos (81,7 ± 0,2 mg de glicose por grama de bagaço) e H2SO4 0,1 M saturado com ozônio, irradiado por micro-ondas por 4 minutos (86,0 ± 0,2 mg de glicose por grama de bagaço), que representam um ganho significativo frente aos 6,8 ± 0,2 mg de glicose por grama de bagaço não tratado. As análises por Calorimetria Exploratória Diferencial (DSC) e por Espectrofotometria no Infravermelho (FTIR-ATR) possibilitaram comparar as modificações no sistema estrutural da parede...The lignocellulosic material of which the sugarcane bagasse is made contains, mainly, polymerized sugars as cellulose and hemicelluloses and polymerized phenolic compounds as lignin. These polysaccharides can be hydrolyzated chemically or enzymatically, giving rise to, among other compounds, fermentable sugars. The aim of this work is to investigate some physicochemical treatments applied to the sugarcane bagasse that favors the release of the maximum amount of fermentable sugars by enzymatic hydrolysis, with a minimal production of alcoholic fermentation inhibitor compounds. Different pre-treatment conditions were tested as different concentrations of sulfuric acid or sodium hydroxide concomitantly with the combinated treatments of ozone, ultrasound and microwaves. Results showed that such processes promoted certain disruption of lignocellulosic complex of the bagasse cell wall, which was related to the concentration of phenolic compounds and reducing sugars. Then, the bagasse was subjected to the action of cellulolytic enzymes and the reducing sugars content was quantified. The conditions in what the maximum amount of these sugars were released were: H2SO4 0.1 M, irradiated by ultrasound for 5 minutes (81.7 ± 0,2 mg/g bagasse) and H2SO4 0.1 M irradiated by microwaves for 4 minutes (86.0 ± 0,2 mg/g bagasse), that represents a significative gain compared to untreated bagasse. Strucural analysis by Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared Spectrophotometry Atennuated Total Reflectance (FTIR-ATR) analysis allowed comparing the structural modifications in the wall after the pretreatments, indicating that ultrasound pretreatments were effective for hemicelluloses desestruturation and decrease in the cellulose crystallinity index while microwave pretreatments were... (Complete abstract click electronic access below)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Estudo computacional do líquido GVL (Gama-valerolactona): Influência da quiralidade nas propriedades termodinâmicas

Besides its properties as a “green solvent”, organic molecule Gamma-valerolactone is also a chiral compound, presenting potential applications in enantioselective processes. Once obtained the adequate parameters for liquid phase simulations, different computational models were employed in order to investigate how chirality influences its thermodynamic properties. Under thermodynamic equilibrium, neither energetic nor structural differences between GVL racemic mixture and its enantiomeric pure counterparts were observed. Analysis of the most stable dimers extracted from a Monte Carlo simulation of the racemic mixture revealed subtle interaction energy differences when homochiral (RR and SS) pairs were compared to heterochiral (RS and SR) pairs, which indicated a subtle energetic preference for the homochiral ones. On the other hand, significant chiral discrimination were obtained using nonequilibrium methods. Solvation process for both R and S enantiomers of 1-chloro-1-aminoethane (CAE) in liquid SGVL via Thermodynamic Perturbation Theory resulted in a chemical potential nearly 3;3 kJ mol-1 lower for R-CAE when compared to S-CAE, indicating that the utilization of GVL as a chiral liquid could increase the yield of processes involving chiral species in condensed phase. Binding process of GVL molecules giving rise to both homochiral (SS) and heterochiral (SR) dimers in vacuum, via Umbrella Sampling method, could show that although both pairs had similar binding free energy values, major differences could be observed on these free energy profiles when higher molecular contact was imposed by Umbrella Sampling spatial confinement. Such binding process of GVL molecules was also studied in both RGVL and SGVL liquids. Thus, although lower binding free energy values were obtained, a nearly 20 % difference could be observed due to solvent chirality.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)A molécula orgânica Gama-valerolactona (GVL), além de possuir características que a classificam como “solvente verde”, é uma molécula quiral, apresentando potenciais aplicações em processos enantiosseletivos diversos. Uma vez refinados os parâmetros de simulação adequados para que dados termodinâmicos do líquido pudessem ser reproduzidos, diferentes modelos computacionais foram empregados na investigação do potencial deste líquido como meio quiral para químicos processos diversos. Em situações de equilíbrio termodinâmico não foram observadas diferenças energéticas ou estruturais quando líquidos enantiometicamente puros foram comparados com a mistura racêmica, tampouco foram observadas quaisquer diferenças nas interações entre enantiômeros R e S na mistura racêmica de GVL. A análise dos pares GVL-GVL mais estáveis extraídos ao longo de uma simulação de Monte Carlo da mistura racêmica foi capaz de revelar diferenças sutis nas energias de interação obtidas para pares homoquirais (R-R e S-S) e para pares heteroquirais (R-S e S-R), mostrando um sutil favorecimento energético para os pares homoquirais. Discriminação quiral mais significativa foi obtida com a utilização de métodos fora do equilíbrio termodinâmico. O processo de solvatação dos enantiômeros R e S da molécula quiral 1-cloro-1-aminoetano (CAE) no líquido quiral SGVL via Perturbação Termodinâmica resultou em um potencial químico cerca de −3,3 kJ mol −1 menor para enantiômero R-CAE, indicando que a utilização de GVL como líquido quiral tem a capacidade de aumentar o rendimento de processos que envolvam espécies quirais em fase condensada. Também foi estudado o processo de associação de pares GVL-GVL homoquirais (S-S) e heteroquirais (S-R) no vácuo com a utilização do método de Umbrella Sampling. Embora ambos os pares tenham apresentado valores praticamente iguais de energia livre para o processo de associação, puderam ser observadas diferenças significativas em situações de confinamento espacial, no qual a separação entre as moléculas é menor do que a distância de equilíbrio e há maior contato molecular. Com metodologia similar, o processo de associação de pares GVL-GVL homoquirais (R-R ou S-S) e heteroquirais (S-R) também foi estudado na presença de solvente RGVL ou SGVL. Assim, embora valores significativamente menores de energia livre tenham sido obtidos, diferenças de aproximadamente 20 % puderam ser observadas em função da quiralidade do solvente

Frequency of GJB2 mutations in patients with nonsyndromic hearing loss from an ethnically characterized Brazilian population

Introduction: In different parts of the world, mutations in the GJB2 gene are associated with nonsyndromic hearing loss, and the homozygous 35delG mutation (p.Gly12Valfs*2) is a major cause of hereditary hearing loss. However, the 35delG mutation is not equally prevalent across ethnicities, making it important to study other mutations, especially in multiethnic countries such as Brazil. Objective: This study aimed to identify different mutations in the GJB2 gene in patients with severe to profound nonsyndromic sensorineural hearing loss of putative genetic origin, and who were negative or heterozygote for the 35delG mutation. Methods: Observational study that analyzed 100 ethnically characterized Brazilian patients with nonsyndromic severe to profound sensorineural hearing loss, who were negative or heterozygote for the 35delG mutation. GJB2 mutations were detected by DNA-based sequencing in this population. Participants’ ethnicities were identified as Latin European, Non-Latin European, Jewish, Native, Turkish, Afro-American, Asian and Others. Results: Sixteen participants were heterozygote for the 35delG mutation; 14 participants, including three 35delG heterozygote's, had nine different alterations in the GJB2 gene. One variant, p.Ser199Glnfs*9, detected in two participants, was previously unreported. Three variants were pathogenic (p.Trp172*, p.Val167Met, and p.Arg75Trp), two were non-pathogenic (p.Val27Ile and p.Ile196Thr), and three variants were indeterminate (p.Met34Thr, p.Arg127Leu, and p.Lys168Arg). Three cases of compound heterozygosity were detected: p.[(Gly12Valfs*2)];[(Trp172*)], p.[(Gly12Valfs*2)](;)[(Met34Thr)], and p.[(Gly12Valfs*2)(;)[(Ser199Glnfs*9)]). Conclusion: This study detected previously unclassified variants and one case of previously unreported compound heterozygosity. Resumo: Introdução: Em diferentes partes do mundo, mutações do gene GJB2 estão associadas a perda auditiva não sindrômica e a mutação homozigótica 35delG (p.Gly12Valfs*2) é uma das principais causas de perda auditiva hereditária. No entanto, a mutação 35delG não é igualmente prevalente em todas as etnias, faz com que seja importante estudar outras mutações, especialmente em países multiétnicos, como o Brasil. Objetivo: Identificar diferentes mutações no gene GJB2 em pacientes com perda auditiva neurossensorial grave ou profunda não sindrômica de origem genética putativa e negativos ou heterozigotos para a mutação 35delG. Método: Estudo observacional que analisou 100 pacientes brasileiros caracterizados etnicamente, com perda auditiva neurossensorial grave ou profunda não sindrômica, negativos ou heterozigotos para a mutação 35delG. As mutações de GJB2 foram detectadas por sequenciamento baseado no DNA nessa população. As etnias dos participantes foram identificadas como latino-europeia, não latino-europeia, judaica, nativa, turca, negra, asiática e outras. Resultados: Dezesseis participantes eram heterozigotos para a mutação 35delG e 14, incluindo três heterozigotos para 35delG, apresentaram nove alterações no gene GJB2. Uma variante, p.Ser199Glnfs*9, detectada em dois participantes, não havia sido relatada anteriormente. Três variantes eram patogênicas (p.Trp172*, p.Val167Met, e p.Arg75Trp), duas não patogênicas (p.Val27Ile e p.Ile196Thr) e três indeterminadas (p.Met34Thr, p.Arg127Leu, e p.Lys168Arg). Três casos de heterozigosidade composta foram detectados: p.[(Gly12Valfs*2)];[(Trp172*)], p.[(Gly12Valfs*2)](;)[(Met34Thr)], e p.[(Gly12Valfs*2)(;)[(Ser199Glnfs*9)]). Conclusão: Este estudo detectou variantes não classificadas anteriormente e um caso de heterozigosidade composta ainda não relatada. Keywords: Hearing loss, Deafness, Genetics, Palavras-chave: Perda de audição, Surdez, Genétic

Impact of Rural Grid-Connected Photovoltaic Generation Systems on Power Quality

Photovoltaic (PV) generation systems have been increasingly used to generate electricity from renewable sources, attracting a growing interest. Recently, grid connected PV micro-generation facilities in individual homes have increased due to governmental policies as well as greater attention by industry. As low voltage (LV) distribution systems were built to make energy flow in one direction, the power feed-in of PV generation in rural low-voltage grids can influence power quality (PQ) as well as facility operation and reliability. This paper presents results on PQ analysis of a real PV generation facility connected to a rural low-voltage grid. Voltage fluctuations and voltage harmonic contents were observed. Statistical analysis shows a negative impact on PQ produced by this PV facility and also that only a small fraction of the energy available during a sunny day is converted, provoking losses of revenue and forcing the converter to work in an undesirable operating mode. We discuss the disturbances imposed upon the grid and their outcome regarding technical and economic viability of the PV system, as well as possible solutions. A low-voltage grid strengthening has been suggested and implemented. After that a new PQ analysis shows an improvement in the impact upon PQ, making this facility economically viable

Correction: Effect of caffeine on neuromuscular function following eccentric-based exercise.

[This corrects the article DOI: 10.1371/journal.pone.0224794.]

Effect of caffeine on neuromuscular function following eccentric-based exercise.

This study investigated the effect of caffeine on neuromuscular function, power and sprint performance during the days following an eccentric-based exercise. Using a randomly counterbalanced, crossover and double-blinded design, eleven male jumpers and sprinters (age: 18.7 ± 2.7 years) performed a half-squat exercise (4 x 12 repetitions at 70% of 1 RM), with eccentric action emphasized by using a flexible strip attached to their knees (Tirante Musculador®). They ingested either a capsule of placebo or caffeine (5 mg.kg-1 body mass) 24, 48 and 72 h after. Neuromuscular function and muscle power (vertical countermovement-jump test) were assessed before and after the half-squat exercise and 50 min after the placebo or caffeine ingestion at each time-point post-exercise. Sprint performance was measured at pre-test and 75 min after the placebo or caffeine ingestion at each time-point post-exercise. Maximal voluntary contraction (overall fatigue) and twitch torque (peripheral fatigue) reduced after the half-squat exercise (-11 and -28%, respectively, P 0.05) and were not affected by caffeine ingestion (P > 0.05). The voluntary activation (central fatigue) and sprint performance were not altered throughout the experiment and were not different between caffeine and placebo. However, caffeine increased height and power during the vertical countermovement-jump test at 48 and 72 h post half-squat exercise, when compared to the placebo (P < 0.05). In conclusion, caffeine improves muscle power 48 and 72 h after an eccentric-based exercise, but it has no effect on neuromuscular function and sprint performance

Perforated acute abdomen in a patient with COVID-19: an atypical manifestation of the disease

Introduction: The Coronavirus belongs to a family of RNA viruses that can cause respiratory infection, with the possibility of gastrointestinal manifestations in approximately 5–50% of the cases. Objective: To report a surgical case with a diagnosis of COVID-19 that developed acute perforated abdomen and pneumothorax. Case report: This was an 80-year-old female patient with respiratory symptoms, with dry cough and fever and diffuse abdominal pain with signs of peritonitis. She had leukocytosis, kidney dysfunction and an increase in D-dimer with positive PCR for COVID. Computed tomography of the chest and abdomen showed pneumothorax on the right and extensive pneumoperitoneum. Conclusion: The presentation of COVID-19 with severe pulmonary and abdominal complications requires specialized and emergency treatments, but it has high mortality rates. Resumo: Introdução: O coronavírus pertence a uma família de vírus RNA que pode causar infecção respiratória com possibilidade de manifestações gastrintestinais em torno de 5% a 50% dos casos. Objetivo: Relatar caso operado com diagnóstico de COVID-19 e evolução com abdome agudo perfurativo e pneumotórax. Relato do caso: Paciente do sexo feminino de 80 anos com sintomas respiratórios com tosse seca e febre e dor abdominal difusa com sinais de peritonite. Apresentava leucocitose, disfunção renal e aumento de D-dímero com PCR positivo para COVID. Tomografia computadorizada de tórax e abdome demonstrando pneumotórax à direita e extenso pneumoperitônio. Conclusão: A apresentação do COVID-19 com sérias complicações pulmonar e abdominal requer tratamentos especializados e em regime de emergência, entretanto com altas taxas de mortalidade