Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Leishmania infantum infection rate in dogs housed in open-admission shelters is higher than of domiciled dogs in an endemic area of canine visceral leishmaniasis. Epidemiological implications.

Canine visceral leishmaniasis (CVL) is caused by Leishmania infantum and is endemic in many areas of southeastern Brazil. We have hypothesized that the prevalence of infection by L. infantum in dogs housed in open-admission animal shelters is beyond the range of 3.4 - 9.6% reported among dogs domiciled in similar CVL-endemic areas. Hence, this study aimed to determine the rate of L. infantum infection among dogs maintained in shelters and to investigate the epidemiology of CVL in such environments by analyzing hematological and biochemical parameters. A total of 627 dogs from 17 different shelters across the State of Minas Gerais were screened using the Dual-Path Platform test and enzyme-linked immunosorbent assay and 211 (33.6%) were found to be seropositive in both tests. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on skin, bone marrow and lymphoid tissues of 118 seropositive dogs with inconclusive CVL clinical diagnosis and, of these, 78 (66.1%) were PCR+ for L. infantum and 7 (5.9%) were PCR+ for L. amazonensis. One dog presented a PCR-RFLP profile that was consistent with co-infection by both parasites. Leishmania amazonensis DNA was detected in skin samples of six single-infected dogs and this constitutes a novel finding. Dogs infected only with L. amazonensis were less debilitated than those infected by L. infantum, which showed typical clinical manifestations of CVL. The co-infected dog showed only mild clinical signs. The results presented herein not only support our original hypothesis but also suggest that dogs are potential reservoirs of L. amazonensis. Public health authorities should acknowledge their responsibility towards animals in collective shelters, recognize that they are potential foci of zoonotic diseases, and establish proper functioning directives to minimize transmission to humans and to other dogs.

Effect of Early Treatment with Ivermectin among Patients with Covid-19.

BACKGROUND: The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear. METHODS: We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 µg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization. RESULTS: A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events. CONCLUSIONS: Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Spotting plants' microfilament morphologies and nanostructures.

The tracheary system of plant leaves is composed of a cellulose skeleton with diverse hierarchical structures. It is built of polygonally bent helical microfilaments of cellulose-based nanostructures coated by different layers, which provide them high compression resistance, elasticity, and roughness. Their function includes the transport of water and nutrients from the roots to the leaves. Unveiling details about local interactions of tracheary elements with surrounding material, which varies between plants due to adaptation to different environments, is crucial for understanding ascending fluid transport and for tracheary mechanical strength relevant to potential applications. Here we show that plant tracheary microfilaments, collected from Agapanthus africanus and Ornithogalum thyrsoides leaves, have different surface morphologies, revealed by nematic liquid crystal droplets. This results in diverse interactions among microfilaments and with the environment; the differences translate to diverse mechanical properties of entangled microfilaments and their potential applications. The presented study also introduces routes for accurate characterization of plants' microfilaments.

Reversible water driven chirality inversion in cellulose-based helices isolated from Erodium awns.

Among the movements observed in some cellulosic structures produced by plants are those that involve the dispersion and burial of seeds, as for example in Erodium from the Geraniaceae plant family. Here we report on a simple and efficient strategy to isolate and tune cellulose-based hygroscopic responsive materials from Erodium awns' dead tissues. The stimuli-responsive material isolated forms left-handed (L) or right-handed (R) helical birefringent transparent ribbons in the wet state that reversibly change to R helices when the material dries. The humidity-driven motion of dead tissues is most likely due to a composite material made of cellulose networks of fibrils imprinted by the plant at the nanoscale, which reinforces a soft wall polysaccharide matrix. The inversion of the handedness is explained using computational simulations considering filaments that contract and expand asymmetrically. The awns of Erodium are known to present hygroscopic movements, forming R helices in the dry state, but the possibility of actuating chirality via humidity suggests that these cellulose-based skeletons, which do not require complicated lithography and intricate deposition techniques, provide a diverse range of applications from intelligent textiles to micro-machines.

Cellulose-Based Biomimetics and Their Applications.

Nature has been producing cellulose since long before man walked the surface of the earth. Millions of years of natural design and testing have resulted in cellulose-based structures that are an inspiration for the production of synthetic materials based on cellulose with properties that can mimic natural designs, functions, and properties. Here, five sections describe cellulose-based materials with characteristics that are inspired by gratings that exist on the petals of the plants, structurally colored materials, helical filaments produced by plants, water-responsive materials in plants, and environmental stimuli-responsive tissues found in insects and plants. The synthetic cellulose-based materials described herein are in the form of fibers and films. Fascinating multifunctional materials are prepared from cellulose-based liquid crystals and from composite cellulosic materials that combine functionality with structural performance. Future and recent applications are outlined.

Cause-specific mortality in a cohort of Brazilian patients with type 1 diabetes.

AIMS: To assess cause-specific mortality in a cohort of patients with type 1 diabetes (T1D) followed at an university hospital (tertiary level, Rio de Janeiro city) and an outpatient clinic (secondary level, Bauru city) both in Brazil's southeast, and associations of survival with gender, age at diagnosis, self-reported ethnicity and diabetes duration. METHODS: Our study is based on a cohort of patients with T1D whose vital status was determined as of December 31, 2015. The causes of mortality were determined by death certificates and outpatient clinic records. RESULTS: Among 986 patients, (54.4%) females, (74.8%) Caucasians, 886 (89.9%) were alive, 62 (6.3%) had died, and in 38 (3.9%) the vital status was unknown. Median age at death [interquartile range] and diabetes duration until death were 30.0 [13] and 15.6 [10] years, respectively. Considering those who died (n = 62), most patients (about 70%) died from end-stage renal disease, macrovascular disease or acute complications of diabetes, mainly diabetic ketoacidosis. The other causes of mortality were infections, fatal accidents and non-diabetes-related. The standardized mortality ratio was 3.13 [2.35-4.08] in those aged under 40. In a multivariate Cox model, "age < 40 years" and "year of diagnosis" were the only significant variables with hazard ratios of 6.259 [(3.100-12.639), p < 0.001] and 0.915 [(0.880-0.951), p < 0.001], respectively. CONCLUSIONS: Our study shows that patients with T1D had a threefold increase in mortality. The specific causes of mortality were mainly diabetes-related chronic complications; however, acute complications, especially diabetic ketoacidosis, persisted as an important cause of mortality.

Yacon (Smallanthus sonchifolius) as a Food Supplement: Health-Promoting Benefits of Fructooligosaccharides.

Yacon (Smallanthus sonchifolius), a perennial plant of the family Asteraceae native to the Andean regions of South America, is an abundant source of fructooligosaccharides (FOS). This comprehensive review of the literature addressed the role of yacon supplementation in promoting health and reducing the risk of chronic diseases. According to several preclinical and clinical trials, FOS intake favors the growth of health-promoting bacteria while reducing pathogenic bacteria populations. Moreover, the endproducts of FOS fermentation by the intestinal microbiota, short chain fatty acids (SCFA), act as substrates or signaling molecules in the regulation of the immune response, glucose homeostasis and lipid metabolism. As a result, glycemic levels, body weight and colon cancer risk can be reduced. Based on these findings, most studies reviewed concluded that due to their functional properties, yacon roots may be effectively used as a dietary supplement to prevent and treat chronic diseases.

Mortalidade de bovinos zebuínos por hipotermia em Mato Grosso do Sul / Mortality of zebu cattle by hypothermia in Mato Grosso do Sul, Brazil

O presente trabalho teve por objetivo descrever a ocorrência periódica de mortalidade de bovinos por hipotermia após inversão térmica no estado de Mato Grosso do Sul. São relatados 16 surtos encaminhados ao Laboratório de Patologia Animal da FAMEZ/UFMS, ocorridos de agosto de 2000 a julho de 2010, em 13 municípios do Estado. O diagnóstico de hipotermia baseou-se na ocorrência de mortes após queda brusca de temperatura acompanhada de chuvas e ventos, simultaneamente em diversas propriedades, nos sinais clínicos observados e na ausência de lesões macro e microscópicas significativas. Em todos os surtos houve uma queda brusca de temperatura, de até 29ºC, em intervalos de um a quatro dias associada a chuva e vento. Na maioria das vezes a morte dos bovinos ocorreu em locais onde havia escassez de pasto e ausência de abrigos naturais ou artificiais. Os bovinos afetados estavam magros, com baixo escore corporal, e, em grande parte dos casos, eram encontrados mortos nos cantos das invernadas e próximos a cercas no dia seguinte à queda brusca da temperatura. Foram afetados bovinos de diferentes idades. Os sinais clínicos se caracterizavam por cegueira, incoordenação, dismetria, fraqueza, decúbito esternal, movimentos de pedalagem, opistótono, tremores musculares, e dificuldade respiratória e morte. Em 30 bovinos necropsiados os principais achados macroscópicos foram edema subcutâneo, cavitário e pulmonar, e, em alguns casos, histologicamente havia eosinofilia neuronal. A hipotermia é uma importante causa de mortalidade quando bovinos com pobre estado nutricional, pouca disponibilidade e qualidade dos pastos e ausência de abrigos naturais, são submetidos a uma condição de mudança climática com queda brusca de temperatura combinada com ventos fortes e chuvas.

This study describes the periodic mortality of cattle due to hypothermia after thermal inversion in Mato Grosso do Sul, Brazil. Sixteen outbreaks, reported to the Laboratory of Animal Pathology FAMEZ/UFMS, occurred from August 2000 to July 2010 in 13 municipalities of the state. The diagnosis of hypothermia was based on the occurrence of deaths after a sudden decrease in temperature accompanied by rain and wind in several farms simultaneously, on clinical signs and on the absence of significant macroscopic and microscopic lesions. In all outbreaks was a sudden fall of temperature up to29°C at intervals of one to four days together with rain and wind. Most deaths occurred in places with scarce pasture and lack of natural or artificial shelters. The affected cattle were lean, with low body score, and in most cases on the morning following sudden fall in temperature, they were found dead in the corners of wintering and near the fences. Cattle of different ages were affected. Clinical signs were characterized by apparent blindness, incoordination, dysmetria, weakness, sternal recumbency, paddling, opisthotonus, muscle tremors, difficulty in breathing and death. In 30 necropsied animals the main macroscopic findings were subcutaneous, cavity and pulmonary edema. Histologically in some cases neuronal eosinophilia was observed. Hypothermia is an important cause of mortality when cattle, not acclimated, with poor nutritional status, low availability and quality of pasture, and lack of natural shelter, are subjected to climate change with sudden fall in temperature combined with high winds and rain.

Effects of strength, endurance, and concurrent training on aerobic power and dynamic neuromuscular economy in elderly men.

The aim of this study was to investigate the effects of concurrent training on endurance capacity and dynamic neuromuscular economy in elderly men. Twenty-three healthy men (65 ± 4 years) were divided into 3 groups: concurrent (CG, n = 8), strength (SG, n = 8), and aerobic training group (EG, n = 7). Each group trained 3 times a week for 12 weeks, strength training, aerobic training, or both types of training in the same session. The maximum aerobic workload (Wmax) and peak oxygen uptake (VO2peak) of the subjects were evaluated on a cycle ergometer before and after the training period. Moreover, during the maximal test, muscle activation was measured at each intensity by means of electromyographic signals from the vastus lateralis (VL), rectus femoris (RF), biceps femoris long head, and gastrocnemius lateralis to determine the dynamic neuromuscular economy. After training, significant increases in VO2peak and Wmax were only found in the CG and EG (p < 0.05), with no difference between groups. Moreover, there was a significant decrease in myoelectric activity of the RF muscle at 50 (EG), 75 and 100 W (EG and CG) and in the VL for the 3 groups at 100 W (p < 0.05). No change was seen in the electrical signal from the lateral gastrocnemius muscle and biceps femoris. The results suggest specificity in adaptations investigated in elderly subjects, because the most marked changes in the neuromuscular economy occurred in the aerobically trained groups.

1-octen-3-O-alpha-L-arabinopyranosyl-(1 -> 6)-beta-glucopyranoside, a minor substance from the leaves of Kalanchoe pinnata (Crassulaceae)

From the leaves of Kalanchoe pinnata (Crassulaceae), a medicinal plant widely used against inflammatory processes which exhibit a important immunosuppressive and anti-leishmanial activities, was isolated a minor vinylic aliphatic alcohol diglycoside which structure was proposed as the known 1-octen-3-O-alpha-L-arabinopyranosyl-(1 -> 6)-beta-glucopyranoside based on ¹H and 13C mono and bi-dimensional NMR experiments and GC-MS analysis, after successive chromatographic column procedures. This molecule is a water-soluble derivative of the volatile aglicone 1-octen-3-ol that appears to be attractant of pollinators and signalling of defence against herbivores.

A partir das folhas de Kalanchoe pinnata (Crassulaceae), uma planta medicinal amplamente utilizada contra processos inflamatórios e que apresenta importante atividade imunossupressora e anti-leishmania, foi isolado um álcool vinílico diglicosilado minoritário, caracterizado como 1-octeno-3-O-alfa-L-arabinopiranosil-(1 -> 6)-beta-glicopiranosídeo baseado em RMN mono e bi-dimensional e em CG-EM, após sucessivos processos cromatográficos em coluna. Esta molécula é um derivado hidrossolúvel da aglicona 1-octen-3-ol, molécula que atua como atrativo para polinizadores e sinalizador de defesa contra herbivoria.

Helicobacter pylori na doença gastroduodenal em brejo da madre de Deus - Pernambuco / Helicobacter pylori associated whit gastroduodenal disease in Brejo da Madre de Deus - Pernambuco

Brejo da Madre de Deus situada na Zona Agreste de Pernambuco, faz parte do Projeto de Saude Pública no Nordeste - convênio UFPE/Secretaria de Saúde do Estado de Pernambuco/Núcleo de Saúde Pública/Agência Internacional de Cooperação Japonesa (NUSP/JICA). Numa análise preliminar, verificou-se um grande número de pessoas com queixas digestivas e antecedentes familiares de gastrite úlcera e câncer gástrico. A população vive principalmente da agricultura. com registro de uso abusivo de agrotóxicos, fato cogitado na gênese dessas doenças. A descoberta da infecção gastrica pelo Helicobacter pylori determinou mudança na abordagem dessas doenças, justificando a importância desta pesquisa. Foi aplicado questionário acerca das queixas digestivas, antecedentes pessoais e familiares, além das condições sócio-econômicas. Os pacientes que preencheram oos questionparios realizaram endoscopia digestiva e pesquisa do Helicobacter pylori através dos teste de Urese. Os portadores de úlcera gástrica, bem como os suspeitos de neoplasia gástrica submeteram-se a estudo histopatológico da mucosa gástrica. Foram estudados 619 pacientes com idade média de 39,6ñ9,5, sendo 30,0por cento feminino. foram anotadas queixas de dor epigástrica em85,6 por cento, queimor epigástrico em 16,3 por cento, empachamento pós-prandial em 22,3por cento, náusea em 19,9por cento, vômitos em 22,8 por cento, disfagia em 2,6por cento e hemorragia em 1,9por cento. Antecedentes pessoais de agrotóxicos em 25,4por cento, tabagismo em 25,4 por cento, álcool em 34,7por cento, excesso de sal em 33,8 por cento e frituras em 46,4 por cento. Antecedentes familiares de gastrite em 42,6 por cento, úlcera em 19,1 por cento e câncer gástrico em 12,1 por cento. O diagnóstico endoscópico do estômago foi normal em 38,0 por cento. Gastrite em 52,7 por cento, úlcera gástrica em 4,5por cento, câncer gástrico em 1,5por cemto, úlcera duodenal em 11,6por cento, duodenite em 12,6por cento. O Helicobacter pylori esteve presente em 59,4 por cento dos casos e em 77,3 por cento, quando se estudou gastrite. Em conclusão, o Helicobacter Pylori teve alta frequência em Brejo da Madre de Deus e que, provalvelmente, é o fator determinante do alto índice de doenças gastroduodenais, podendo ser coadjuvada pelo uso de agrotóxios