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Aim: As far as is known, the pharmaceutical effects of neem on human B-lymphoblastoid (TK6) cells have not been studied until now. Hence, the present study aimed to obtain neem phenolic extracts for inhibits the proliferation of TK6 cells and explore some possible underlying mechanisms involved in these effects. Methods: Hexane extract (HE) was obtained in the first step. After that, the residual hexane was removed from the neem. The dried neem sample was used in a new extraction for obtaining the ethyl acetate extract (EAE). Total phenolic compounds (TPC) and total flavonoid contents (TFC) were determined by spectrophotometric methods. Lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to evaluate the cytotoxicity in TK6 cells. The stop at G0/G1 cell cycle and inducing apoptosis in the TK6 cells were analyzed by flow cytometry. For deoxyribonucleic acid (DNA) damage evaluation, the alkaline comet test was used. Results: The higher TFC (65.50 mg/g of extract ± 1.17 mg/g of extract) and TPC (52.08 mg of extract ± 0.88 mg of extract) were obtained in EAE compared to HE that was obtained TFC of 14.61 mg/g of extract ± 0.60 mg/g of extract and TPC of 3.20 mg/g of extract ± 1.20 mg/g of extract. EAE was more significantly cytotoxic to TK6 cells than HE. The apoptosis induction was higher after exposure to 15.0 µg/mL of EAE (11.29%) in comparison to 15.0 µg/mL of HE (2.52%). The G0/G1 phase increased from 72% negative control (NC) to 83% after treatment with neem extracts (15 µg/mL). Neem extracts were also able to cause DNA strand breaks in TK6 cells. Conclusions: The extraction residue from neem leaf after hexane extraction is a source important of cytotoxic and genotoxic molecules against TK6 cells, the results also can suggest that the toxic effects in TK6 cells can be provided most likely due to the presence of high content of TPC from neem extracts.

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments lacking efficiency and leading to severe side effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150 nm) and homogeneous (polydispersity index of 0.162) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models (inhibitory concentrations between 12.37 ng/mL and 14.72 ng/mL). Additionally, they also revealed substantial anti-inflammatory activity (inhibitory concentration of 28.98 ng/mL), effects complementary to direct antitumor activity. Niosome safety was also assessed, both in vitro (skin, liver, and kidney cells) and ex vivo (hen’s egg chorioallantoic membrane), and results showed that compound encapsulation increased its safety. Hence, small, and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies. Future research should focus on evaluating the potential of the developed platform in in vivo models.

Background Most of the Brazilian population relies on public healthcare and stroke is a major cause of disability in this country of continental dimensions. There is limited information about access to rehabilitation after stroke in Brazil. Objective To provide comprehensive information about Access to Rehabilitation After discharge from public hospitals in Brazil (AReA study), up to 6 months after stroke. Methods The present study intends to collect information from 17 public health centers in 16 Brazilian cities in the 5 macroregions of the country. Each center will include 36 participants (n = 612). The inclusion criteria are: age ≥ 18 years old; ischemic or hemorrhagic stroke, from 6 months to 1 year prior to the interview; admission to a public hospital in the acute phase after stroke; any neurological impairment poststroke; patient or caregiver able to provide informed consent and answer the survey. Patients can only be recruited in public neurology or internal medicine outpatient clinics. Outcomes will be assessed by a standard questionnaire about rehabilitation referrals, the rehabilitation program (current status, duration in months, number of sessions per week) and instructions received. In addition, patients will be asked about preferences for locations of rehabilitation (hospitals, clinics, or at home). Trial Status The study is ongoing. Recruitment started on January 31st, 2020 and is planned to continue until June 2022. Conclusion The AReA study will fill a gap in knowledge about access to stroke rehabilitation in the public health system in different Brazilian regions.

Background Aphasia, the most common language disorder secondary to stroke, has been associated with increased mortality, longer hospitalization and rehabilitation times, worse performance in daily activities, increased financial burden, and short- and long-term complications. Aphasia can negatively impact functional communication skills, including social networks, social activities, relationships with other people and social support. Objective To evaluate patients with poststroke aphasia in their respective residences to investigate potential predictors of functional communication. Methods The prospective cohort included patients with poststroke aphasia aged 18 years or older who resided in the city of Salvador, Northeastern Brazil. Following discharge from the Stroke Unit (SU), the individuals themselves, or their guardians, were contacted by telephone to schedule a home visit no less than three months after discharge. At baseline, sociodemographic and clinical data were collected, in addition to the scores on the National Institutes of Health Stroke Scale (NIHSS) and modified Barthel Index (mBI). The American Speech-Language-Hearing Association Functional Assessment of Communication Skills for Adults (ASHA FACS) was applied at the patients' homes. Multivariate linear regression was employed using the total score on the ASHA FACS as the outcome of interest. Results A multivariate analysis of the associated factors identified using the linear regression revealed that only functional capacity (as assessed by the mBI) upon discharge from the SU remained as an independent predictor of functional communication performance (β = 0.042; 95% confidence interval [95%CI] = 0.013–0.071; p = 0.002). Conclusion The functional capacity to perform daily activities, evaluated upon discharge from a stroke unit, was identified as a potential predictor of functional communication performance, regardless of the time elapsed after the stroke.

Los youtubers se han convertido en un fenómeno mundial; debido al hecho de pasar más tiempo en casa se amplifica su estatus y relevancia, especialmente entre los niños. El creciente acceso a Internet, la forma fácil e intuitiva de utilizarlo, el control sobre lo que quieren ver, la cercanía al público y la capacidad de sorprender e innovar son algunos de los motivos que hacen a los youtubers tan atractivos. Con una metodología cualitativa, llevada a cabo en dos fases secuenciales de recogida de datos, primero con niños y después con youtubers, se quiere responder a la siguiente pregunta: ¿Qué influencia tienen los youtubers en la formación de la opinión de niños de 8 a 12 años sobre temas de actualidad? Se concluyó que los niños ven a los youtubers como modelos a seguir, y sus contenidos, una fuente de información fiable; admiten haber cambiado su forma de pensar gracias a ellos. Aunque su influencia disminuye a medida que crecen, se demuestra que tienden a adoptar los puntos de vista y las perspectivas compartidas por los youtubers. Es, además, una oportunidad para que los niños aprendan y conozcan temas importantes desde una edad temprana de forma más accesible e interesante.

O presente artigo propõe-se a discutir o uso de estratégias de leitura conforme proposto por Solé (1998) em prol do letramento literário, apresentando uma sequência de aulas implementada em uma turma de 1º ano do Ensino Médio em um colégio de aplicação da Zona da Mata Mineira. Com o intuito de integrar à formação estética necessária a um leitor literário (BARBOSA, 2011) uma formação cidadã — discutindo temas transversais relevantes para a formação crítica e reflexiva contemporânea, com destaque para questões de gênero, raça e classe —, foi desenvolvida uma oficina literária básica (COSSON, 2018) focada no livro Quarto de despejo (1960), de Carolina Maria de Jesus. Esta sequência propunha-se, além do letramento literário, ao desenvolvimento e ao aprimoramento de habilidades de leitura, escrita, oralidade e análise linguística, promovendo a integração entre esses eixos de ensino.

Este texto explica as territorialidades construídas na migração internacional dos africanos para o Brasil, de maneira especial para o Estado do Ceará nas primeiras décadas do século XXI. Para fundamentar a discussão, o caminho teórico-metodológico foi construído a partir de: seleção de conceitos; levantamento bibliográfico e de dados, e pesquisa empírica. Diante do que foi investigado, afirmamos que no Brasil verifica-se a presença desses migrantes em inúmeras unidades federativas: São Paulo, Rio Grande do Sul, Santa Catarina, Rio de Janeiro, Ceará, Paraná e Minas Gerais. A presença dos africanos no Ceará permite com que tenhamos territorialidades e circularidades migratórias múltiplas, já que diversos são os perfis dos sujeitos em mobilidades (estudantes, trabalhadores e investidores). Numa primeira fase da migração, eles fixam residência na cidade de Fortaleza, Redenção e Acarape, mas ao longo do tempo, por não retornarem ao país de origem, constroem territorialidades e realizam circularidade por diversos bairros da cidade de Fortaleza e por diferentes cidades no território cearense. Vale ressaltar que a presença desses migrantes, no recorte empírico evidenciado, tem aumentado significativamente, demonstrando, o papel de centralidade do Ceará nas novas rotas e dinâmicas migratórias configuradas no território brasileiro.

Abstract Objectives The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. Trial design Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. Participants Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. Data Collection: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient’s age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts ( 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. Intervention and comparator Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. Main outcomes The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. Randomization RedCap→ randomization – 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. Blinding (masking) No blinding – Open label format Numbers to be randomized (sample size) Total number of patients 90 (45 per group) Trial Status Trial version 2.0 – ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 Trial registration Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Na pandemia da COVID-19, são muitos os desafios referentes aos fluxos de mobilidade humana. Nesse sentido, objetiva-se analisar mobilidade internacional de refugiados no nordeste brasileiro diante da pandemia e a possível acentuação da vulnerabilidade dos sujeitos migrantes frente a esta conjuntura. O artigo está estruturado em três etapas. Inicialmente, mostrou-se o aparato (nacional e internacional) protetivo referente aos refugiados. Em seguida, analisou-se o desafio do acolhimento dos refugiados e a possibilidade da caracterização acentuada da vulnerabilidade destes por causa da pandemia da COVID-19, e, para tanto, foram utilizados dados do Ministério da Justiça, em especial do Comitê Nacional para os Refugiados (CONARE), do Alto Comissariado das Nações Unidas para os refugiados (ACNUR), e também do Ministério da Saúde. Por fim, é explicada a necessidade de instrumentos/meios que garantam a proteção de refugiados em situações agravadoras de risco, especialmente, diante dos fatos e das consequências da pandemia da COVID-19. A pesquisa usou a metodologia do tipo bibliográfica, de natureza qualitativa, com fins descritivos e exploratórios. Concluiu-se que a pandemia da COVID-19 é elemento configurador da dupla vulnerabilidade da população em situação de refúgio, e, assim, tem-se a emergência de novos marcos regulatórios e de instrumentos que possibilitem a proteção dos refugiados.

ABSTRACT: The evolution in virulence of Puccinia coronata f. sp. avenae has challenged the genetic resistance to crown rust in oat genotypes. New resistance sources are constantly required for yield stabilization and costs reduction. This study aimed to characterize the crown rust resistance of oat genotypes and the disease´s productive and economic impact. Experiments were conducted in two environments, with and without chemical control. Resistance was measured by disease progress, apparent rate of infection, final severity and pustule size. Damages were based on reduction of yield, 1000 grain mass and hectoliter mass. UFRGS16Q6030-2 was immune. In both environments, UFRGS166091-2 and URS Brava exhibited the greatest level of resistance and the smallest grain yield reduction, while URS 22 was highly susceptible, reducing more than 70% of its grain yield. These results surpass the negative impacts of the disease previously reported in oats, particularly related to grain yield. The data presented in this paper highlighted the importance of genetic resistance, particularly partial resistance, for maintaining oat genetic yield potential, reducing environmental contamination with less fungicides, and increasing economic gains with oat cultivation.

Abstract INTRODUCTION: Individuals with human T-cell lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) experience sensorimotor alterations, which can affect functional performance. Virtual reality (VR) videogaming is a therapeutic option, though there is scarce evidence for its use in this population. We aimed to investigate the therapeutic effects of a VR video game on functional mobility, balance, and gait speed in individuals with HAM/TSP. METHODS: We conducted a blinded, crossover clinical trial comprising 29 individuals with HAM/TSP and randomized them into two groups: (1) early therapy: rehabilitative protocol started immediately after the initial evaluation and (2) late therapy: rehabilitative protocol started 10 weeks later. We assessed all participants for balance using the Berg Balance Scale (BBS) scores, functional mobility using the Timed Up and Go (TUG) test, and gait speed using video camera and CvMob software. Differences were considered significant if p

Plant growth analysis is useful for determining adequate management practices and exploring the maximum yield potential of cultivars or hybrids. Canola hybrids with resistance to herbicides have been studied and registered for Brazilian conditions, as they improve weed management in canola crops. This study evaluated the growth of canola hybrids resistant to triazine or imidazolinone herbicides compared to a sensitive hybrid. The experiment was conducted using a completely randomized design, with four replications, in a bifactorial scheme using three hybrids and six sampling times. The canola hybrids used were Hyola 571CL (resistant to imidazolinones), Hyola 555TT (resistant to triazines), and Hyola 61 (sensitive to both herbicides). Height, leaf area, and dry matter of roots, leaves, stems, and shoots of the plants were evaluated at 14, 28, 42, 56, 70, and 119 days after emergence (DAE). The physiological indices absolute growth rate, leaf area ratio, specific leaf area, and net assimilation rate were calculated, and yield indices evaluated. Compared to Hyola 61, the Hyola 555TT hybrid showed lower values of leaf dry matter at 70 DAE, absolute growth rate up to 56 DAE, and net assimilation rate at 14 and 28 DAE, and a higher leaf area ratio at 56 DAE, whereas the hybrid Hyola 571CL presented lower leaf area and lower leaf dry matter at 70 DAE. At flowering, compared to Hyola 61, the hybrid Hyola 571CL presents lower leaf area, and the hybrids Hyola 555TT and Hyola 571CL have lower leaf dry matter accumulation. Differences in the growth of canola hybrids Hyola 555TT, Hyola 571CL and Hyola 61 do not cause differences in their grain yield.

Em dezembro de 2019, uma doença respiratória causada por um novo coronavírus, SARS-CoV-2, foi identificada pela primeira vez na China. Rapidamente assumiu contornos pandémicos, levando a Organização Mundial da Saúde (OMS) a declarar pandemia a COVID-19 no início de março de 2020. Viver uma pandemia, ou outro evento major de saúde pública, não é habitual e testa o sistema de saúde, assim como a resiliência dos profissionais. A reorganização rápida, a flexibilidade dos profissionais e o trabalho interdisciplinar, permitiu coordenar esforços antes da emergência e garantir que os recursos seriam aproveitados em toda a sua extensão. Um dos papéis fundamentais dos farmacêuticos hospitalares é garantir a disponibilidade e o fornecimento oportuno da terapia mais segura e eficaz. Para isso, os farmacêuticos devem planear, identificar e mitigar a escassez de medicamentos (fornecedores limitados de matérias-primas) e intervir aquando da validação da terapêutica, principalmente em contexto off-label, evitando erros de medicação, omissões de terapêuticas habituais, reações adversas e contribuindo para uma “medicina de precisão” num cenário tão desconhecido.

AIM:To identify potential predictors of community integration in individuals after stroke using a residential setting-based strategy. METHOD:A prospective cohort of post-stroke individuals was recruited from the Stroke Unit of the Roberto Santos General Hospital (UAVC-HGRS). All included individuals were aged over 18 years, received a diagnosis of ischemic stroke confirmed by neuroimaging and resided in the city of Salvador (Bahia, Brazil). Following discharge from the stroke unit, the individuals themselves, or their responsible parties, were contacted by telephone to schedule a home visit no less than three months after discharge. All subjects were examined in their homes, at which time the Community Integration Questionnaire (CIQ) was also applied. A robust linear regression model was used to assess community reintegration using CIQ score as the outcome variable. RESULTS:A total of 124 individuals effectively fulfilled the eligibility criteria: 51.6% were females, the median (IQR) age was 63(53-69) years, 82.3% were non-white, 53.2% were married, the median (IQR) of years of schooling was 6 (4-12) and family income averaged two minimum monthly wages. Investigated individuals presented a median (IQR) NIH Stroke Scale (NIHSS) score of 7 (4-12). Multivariate linear regression identified the following independent predictors of community integration: age (β = -0.095; 95% CI = -0.165 to -0.025; p = 0.008), diabetes mellitus (β = -2.348; 95% CI = -4.125 to -0.571; p = 0.010), smoking habit (β = -2.951; 95% CI = -5.081 to -0.821; p = 0.007), functional capacity upon hospital discharge (β = 0.168; 95% CI = 0.093 to 0.242; p =

Thymus neoplasms are frequently related to paraneoplastic autoimmune manifestations. Its most common associations are myasthenia gravis and pure red cell aplasia. Aplastic anemia has been increasingly documented as an initial presentation of thymoma. Nevertheless, its development after successful surgical resection of thymoma is a rare condition. We report a case of a 53-year-old man with severe aplastic anemia preceded by amegakaryocytic thrombocytopenia three years after thymectomy with no signs of disease recurrence. He underwent immunosuppressive therapy with cyclosporine 5 mg/kg/day and prednisone 2 mg/kg/day for six weeks. Considering the availability of a compatible donor, allogeneic stem cell transplantation was carried out. However, the patient died 11 days after transplant. A literature review was conducted, and another ten cases of aplastic anemia, diagnosed three months to four years after thymectomy, were identified. These cases suggest persistence of peripheral self-reactive T lymphocytes even years after tumor definitive treatment.

Abstract Purpose: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. Methods: Wistar rats (n=62) were allocated into four groups: “Ileal Resection and Anastomosis” vs. “Laparotomy”, each one split into “Postoperative Teduglutide Administration” vs. “No Treatment”; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining). Results: Postoperative teduglutide treatment was associated with higher cellular viability index and lower early apoptosis ratio at the seventh day; higher cytosolic peroxides level at the third day and mitochondrial overgeneration of reactive species at the seventh day; higher tissue concentration of IL-4 and lower local pro-to-anti-inflammatory cytokines ratio at the seventh day. Conclusion: Those findings suggest an intestinal pro-oxidative and anti-inflammatory influence of teduglutide on the peri-operative context with a potential interference in the intestinal anastomotic healing.

A aveia preta (Avena strigosa Schreb.) é uma cultura de grande interesse para agropecuária no Sul do Brasil. O objetivo deste estudo foi avaliar a qualidade fisiológica e sanitária de sementes de aveia preta tratadas com Trichoderma spp. e fludioxonil de forma isolada e combinada. Os tratamentos utilizados foram: sementes imersas em água (controle), sementes microbiolizadas com Trichoderma spp., sementes tratadas com fludioxonil e, sementes tratadas com a combinação Trichoderma spp.+ fludioxonil. A combinação Trichoderma spp.+ fludioxonil exibiu a maior eficácia no controle de fungos presentes em sementes de aveia preta, no entanto, reduziu o crescimento inicial das plantas.

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