Conjoined twins: twenty years' experience at a reference center in Brazil

OBJECTIVE: This study reports on the experience of one hospital regarding the surgical aspects, anatomic investigation and outcomes of the management of 21 conjoined twin pairs over the past 20 years. METHODS: All cases of conjoined twins who were treated during this period were reviewed. A careful imaging evaluation was performed to detail the abdominal anatomy (particularly the liver), inferior vena cava, spleen and pancreas, either to identify the number of organs or to evaluate the degree of organ sharing. RESULTS: There were eight sets of ischiopagus twins, seven sets of thoracopagus twins, three sets of omphalopagus twins, two sets of thoraco-omphalo-ischiopagus twins and one set of craniopagus twins. Nine pairs of conjoined twins could not be separated due to the complexity of the organs (mainly the liver and heart) that were shared by both twins; these pairs included one set of ischiopagus twins, six sets of thoracopagus twins and one set of thoraco-omphalo-ischiopagus twins. Twelve sets were separated, including seven sets of ischiopagus twins, three sets of omphalopagus twins, one set of thoracopagus twins and one set of craniopagus conjoined twins. The abdominal wall was closed in the majority of patients with the use of mesh instead of the earlier method of using tissue expanders. The surgical survival rate was 66.7%, and one pair of twins who did not undergo separation is currently alive. CONCLUSION: A detailed anatomic study of the twins and surgical planning must precede separation. A well-prepared pediatric surgery team is sufficient to surgically manage conjoined twins

Influência do resíduo líquido do sisal (Agave sisalana, Perrine) sobre a eclosão de ovos e o desenvolvimento larvar, in vitre, de nematóides gastrintestinais de ovinos.

A utilização do sisal na obtenção de produtos com ação antiparasitária é uma alternativa de diversificação da exploração do setor agropecuário. O objetivo deste estudo foi avaliar a ação do resíduo líquido de Agave sisalana sobre o desenvolvimento, in vitro, de nematóides gastrintestinais de ovinos. O resíduo líquido das folhas de A. sisalana obtido pelo processo de desfibramento, foi utilizado nos testes de eclosão de ovos (TEO) e desenvolvimento larvar (TDL) de nematóides gastrintestinais (NGI) de ovinos. Houve inibição da eclosão de ovos e o percentual de inibição aumentou significativamente (p<0,05) com o aumento da concentração do resíduo do sisal. As CE50 e CE95 para inibição da eclosão de ovos foram, respectivamente, 6,78 e 23,06mg/mL. A inibição do desenvolvimento de larvas no TDL variou entre zero e 100%. Os testes in vitro utilizados para avaliar a ação do resíduo líquido da folha da A. sisalana sobre ovos e larvas de NGI demonstram o potencial antiparasitário do sisal

Cytotoxicity effect of alkaloidal extract from Prosopis juliflora Sw. D.C. (Algaroba) pods on glial cells

A Prosopis juliflora é amplamente utilizada na alimentação humana e de várias espécies animais, especialmente bovinos. Quadros de intoxicação por esta planta, nesta espécie, têm sido relatados, principalmente quando a mesma é oferecida como única fonte alimentar, desencadeando uma doença de sintomatologia nervosa. Neste estudo, objetivou-se avaliar os efeitos in vitro da fração de alcalóides totais (FA) extraída das vagens da Prosopis juliflora utilizando cultura primária de astrócitos obtidos do córtex cerebral de ratos como modelo de estudo. A avaliação da atividade mitocondrial pelo teste do MTT demonstrou a citotoxicidade em 30 µg/ml da FA após 24 h. As concentrações de 0,3 e 3 µg/ml da FA induziram um aumento da atividade mitocondrial, indicando reatividade celular. Testes imunocitoquímicos para a GFAP, principal proteína de citoesqueleto de astrócitos, revelaram alterações morfológicas nas células após tratamento com 0,3 e 3 µg/ml da FA por 72 h. Tais resultados são consoantes à análise desta proteína por westernblot, quando as culturas foram tratadas com 0,3 e 3 µg/ml da FA por 72 h, demonstrando interferências na regulação da expressão da GFAP. A expressão de vimentina não foi significativamente alterada em nenhuma das concentrações testadas. Estes resultados sugerem que os alcalóides da P. juliflora induzem a reatividade astrocitária, o que pode estar envolvido nos efeitos neurotóxicos providos pelo consumo desta planta.Prosopis juliflora is largely used for feeding cattle and humans. Neurological signals have been reported in cattle due to intoxication with this plant. In this study, an alkaloidal fraction (AF) obtained from P. juliflora pods was tested on astrocyte primary cultures. Astrocytes display physiological functions essential to development, homeostasis and detoxification in the central nervous system (CNS). These cells are known for their role on energetic support and immune response in the CNS. Concentrations between 0.03 to 30 µg/ml AF were assayed for 24 - 72 h. The mitochondrial activity, assayed by MTT test, showed cytotoxicity at 30 µg/ml AF after 24 h. At concentrations ranging between 0.3 - 3 µg/ml, the AF induced an increase on mitochondrial activity, indicating cell reactivity. Immunocytochemistry assay for GFAP cytoskeletal protein, revealed alterations on cell morphology after treatment with 0.3 - 3 µg/ml AF for 72 h. This result corroborates with western blot analysis when cells treated with 0.3 - 3 µg/ml AF for 72 h showed GFAP upregulation. The vimentin expression was not significantly altered in all tested concentrations. These results suggest that alkaloids induce astrocyte reactivity and might be involved in the neurotoxic effects induced by P. juliflora consumption

COVID-19 vaccination produces exercise-responsive SARS-CoV-2-specific T-cells regardless of infection history

Purpose: The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) specific T-cells and neutralizing antibodies during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019 (COVID-19). We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter neutralizing antibody titers. Methods: 18 healthy participants completed a 20 min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine. All major leukocyte subtypes were enumerated before, during, and after exercise by flow cytometry, and immune responses to SARS CoV-2 were determined using whole blood peptide stimulation assays, T-cell receptor (TCR) sequencing, and SARS-CoV-2 neutralizing antibody serology. Results: COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise. However, noninfected participants had a significantly reduced mobilization of CD4+ and CD8+ naive T-cells, as well as CD4+ central memory T-cells, after vaccination (synthetic immunity group); this was not seen after vaccination in those with prior SARS CoV-2 infection (hybrid immunity group). Acute exercise after vaccination robustly mobilized SARSCoV-2 specific T-cells to blood in an intensity-dependent manner. Both groups mobilized T-cells that reacted to spike protein; however, only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens. Neutralizing antibodies increased significantly during exercise only in the hybrid immunity group. Conclusion: These data indicate that acute exercise mobilizes SARS CoV-2-specific Tcells that recognize spike protein and increases the redistribution of neutralizing antibodies in individuals with hybrid immunity

Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice

BackgroundEvery bout of exercise mobilizes and redistributes large numbers of effector lymphocytes with a cytotoxic and tissue migration phenotype. The frequent redistribution of these cells is purported to increase immune surveillance and play a mechanistic role in reducing cancer risk and slowing tumor progression in physically active cancer survivors. Our aim was to provide the first detailed single cell transcriptomic analysis of exercise-mobilized lymphocytes and test their effectiveness as a donor lymphocyte infusion (DLI) in xenogeneic mice engrafted with human leukemia.MethodsPeripheral blood mononuclear cells (PBMCs) were collected from healthy volunteers at rest and at the end of an acute bout of cycling exercise. Flow cytometry and single-cell RNA sequencing was performed to identify phenotypic and transcriptomic differences between resting and exercise-mobilized cells using a targeted gene expression panel curated for human immunology. PBMCs were injected into the tail vein of xenogeneic NSG-IL-15 mice and subsequently challenged with a luciferase tagged chronic myelogenous leukemia cell line (K562). Tumor growth (bioluminescence) and xenogeneic graft-versus-host disease (GvHD) were monitored bi-weekly for 40-days.ResultsExercise preferentially mobilized NK-cell, CD8+ T-cell and monocyte subtypes with a differentiated and effector phenotype, without significantly mobilizing CD4+ regulatory T-cells. Mobilized effector lymphocytes, particularly effector-memory CD8+ T-cells and NK-cells, displayed differentially expressed genes and enriched gene sets associated with anti-tumor activity, including cytotoxicity, migration/chemotaxis, antigen binding, cytokine responsiveness and alloreactivity (e.g. graft-versus-host/leukemia). Mice receiving exercise-mobilized PBMCs had lower tumor burden and higher overall survival (4.14E+08 photons/s and 47%, respectively) at day 40 compared to mice receiving resting PBMCs (12.1E+08 photons/s and 22%, respectively) from the same donors (p&lt;0.05). Human immune cell engraftment was similar for resting and exercise-mobilized DLI. However, when compared to non-tumor bearing mice, K562 increased the expansion of NK-cell and CD3+/CD4-/CD8- T-cells in mice receiving exercise-mobilized but not resting lymphocytes, 1-2 weeks after DLI. No differences in GvHD or GvHD-free survival was observed between groups either with or without K562 challenge.ConclusionExercise in humans mobilizes effector lymphocytes with an anti-tumor transcriptomic profile and their use as DLI extends survival and enhances the graft-versus-leukemia (GvL) effect without exacerbating GvHD in human leukemia bearing xenogeneic mice. Exercise may serve as an effective and economical adjuvant to increase the GvL effects of allogeneic cell therapies without intensifying GvHD

Aerobic Exercise decreases NAFLD, but promotes liver inflammation in PPAR-alpha knockout mice via PPAR-gamma inhibition.

A NAFLD é uma das principais patologias de fígado. Estudos reportam o exercício físico como um dos principais alvos terapêuticos para esta doença. Verificamos se o treinamento melhora a resistência à insulina, inflamação e esteatose hepática causados pela dieta hiperlipídica (HF) e se o PPAR-alpha está envolvido neste processo. Animais selvagens C57BL6 (WT) e knockout para PPAR&alpha; (KO) foram alimentados com dieta padrão ou HF durante 12 semanas e treinados por 8 semana. Metade dos animais KO treinados receberam rosiglitazona. A dieta HF aumentou TAG hepático, e resistência periférica à insulina levando a NALFD. O treinamento foi eficiente em reduzir esses parâmetros em ambos genótipos. O desenvolvimento da NAFLD não foi associado à inflamação hepática, entretanto animais KO treinados apresentaram uma resposta inflamatória exacerbada, causada pela redução de PPAR&gamma;. Quando eles receberam rosi apresentaram melhora no quadro inflamatório hepático e na resistência à insulina. O exercício diminuiu os danos causados pela dieta HF independente do PPAR&alpha;; a ausência do PPAR&alpha; junto com exercício leva a queda na expressão de PPAR&gamma;, e a uma resposta inflamatória exacerbada, que é revertida pela administração da rosiglitazona.NAFLD is one of the main liver diseases. Studies have shown the beneficial effects of exercise on reverse NAFLD. We verify whether exercise improve insulin resistance, liver inflammation and steatohepatitis caused by a high fat diet (HF) and whether PPAR&alpha; is involved in these actions. C57BL6 wild type (WT) and PPAR-&alpha; knockout (KO) mice were fed with a standard (SD) or HF during 12 weeks and trained on a treadmill during 8 weeks, half of KO trained animals received 15mg/kg/day of rosiglitazone. HF diet increased TAG in the liver and peripheral insulin resistance leading to NAFLD. Exercise reduced all this parameters in both animals genotype. NAFLD was not associated with inflammation, however KO mice when trained presented an inflammatory response that was caused by a decrease on PPAR&gamma;. When these mice were treated with rosiglitazone, they presented decrease on inflammatory cytokines as well as improvement on insulin sensitivity. Exercise improved the damage caused by a HF independently of PPAR&alpha; and the absence of PPAR&alpha; together with exercise leads to decrease on PPAR&gamma; expression and an inflammatory response, which was attenuated by rosiglitazone administration

The effects of probiotic supplementation on the immune cells and on upper respiratory tract infection in endurance runners.

A suplementação com probióticos apresenta uma importante capacidade imunomoduladora e surge como uma importante estratégia para tratar doenças autoimunes, doenças crônicas, entre outras. Exercícios prolongados de alta intensidade são conhecidos por diminuir a função da células imunológicas, diminuindo a performance do atleta e prejudicando sua recuperação. Nossa hipótese foi de que 30 dias consecutivos de suplementação com probióticos, antes de uma prova de maratona, seria capaz de modular as células do sistema imunológico e diminuir a incidência de infecções oportunistas. 27 maratonistas do sexo masculino foram randomizados de maneira duplo-cega em dois grupos, probiótico e placebo. Os atletas do grupo probiótico receberam 30 saches contendo Bifidobacterium-animalis-subsp.-Lactis (10x10 9) e Lactobacillus-Acidophilus (10x109) + 5 gramas de maltodextrina; os do grupo placebo receberam 30 saches do mesmo peso, cor e sabor, contendo 5 gramas de maltodextrina; eles consumiram 1 sache por dia até o dia da maratona. Foi coletado sangue antes do início da suplementação (basal), um dia antes da corrida (pré), uma hora após a corrida (pós) e 5 dias após a corrida (recuperação). O grupo suplementado com probiótico manteve a população total de linfócitos T CD8+ após a prova, bem como as subpopulações de memória efetora. O probiótico também foi capaz de modular a resposta dos linfócitos ao estímulo. O treinamento e a maratona foram capazes de modular uma subpopulação de linfócitos T duplo negativo (CD3+CD4-CD8-) independente da suplementação. Nenhuma diferença estatística foi encontrada entre os grupos em relação a incidência e severidade dos sintomas associados a infecções do trato respiratório superior.Probiotic supplementation arises as playing an immune-stimulatory role. High-intensity and -volume exercise can inhibit immune cell function, which threatens athletic performance and recovery. We hypothesized that 30 days of probiotic supplementation could stabilize the immune system of athletes preventing immune suppression after a marathon race. Twenty-seven male marathonists were double-blinded randomly into probiotic (Bifidobacterium-animalis-subsp.-Lactis (10x10 9) and Lactobacillus-Acidophilus (10x109) + 5 grams of maltodextrin) and placebo (5 grams of maltodextrin) group. They received 30 sachets and supplemented 1 portion/day during 30 days before the race. Blood was collected 30 days before (rest), 1 day before (pre), 1 hour after (post) and 5 days after the race (recovery). Both chronic and acute exercise modulated a different T lymphocyte population (CD3+CD4-CD8- T-cells), increasing pre-race, decreasing post, and returning to rest values at the recovery. The total number of CD8 T cell and the memory subsets statistically decreased only in the placebo group post-race. Pro-inflammatory cytokine production by stimulated lymphocytes decreased in the probiotic group after the supplementation period. 30 days of probiotic supplementation maintained CD8 T cell and effector memory cell population and played an immunomodulatory role in stimulated lymphocytes. Both, training, and marathon modulated a non-classical lymphocyte population regardless of probiotic supplementation