Conhecimento e aplicação de testes e instrumentos de avaliação em fisioterapia pediátrica e neonatal / Knowledge and application of tests and assessment tools in pediatric and neonatal physical therapy

Introdução: Os instrumentos de avaliação podem permitir a mensuração de déficits funcionais, corroborando para um diagnóstico mais assertivo. Objetivo: Investigar o conhecimento e a aplicação de instrumentos/testes de avaliação em fisioterapia neonatal e pediátrica. Métodos: Observacional, descritivo, de corte transversal, realizado entre dezembro de 2020 e abril de 2021. Foram avaliados o conhecimento e a aplicação de instrumentos/testes de avaliação por fisioterapeutas que atuam em pediatria e/ou neonatologia na cidade de Salvador/BA. A coleta foi realizada através de um formulário online, produzido pelas autoras, e composto por 24 questões. Resultados: A amostra foi composta por 70 participantes, idade média de 32,5 ± 6,6 anos, 95,7% feminino, 32,9% com pós-graduação Lato Sensu, 51,4% atuavam no regime público, 30% trabalhavam em até dois setores. A mensuração da força muscular respiratória foi o teste mais conhecido (94,3%) e a Escala de Estado Funcional Pediátrica (FSS) o instrumento menos conhecido (41,4%) pelos fisioterapeutas. O instrumento/teste mais e menos aplicados na prática clínica foram, respectivamente, a mensuração da força muscular respiratória (47,1%) e o Denver II (71,4%). Conclusão: Apesar de haver maior frequência de fisioterapeutas que relataram conhecer os instrumentos/testes analisados, houve predominância da não aplicação destes na prática clínica.

Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy.

Bone marrow (BM) provides chemoprotection for acute lymphoblastic leukemia (ALL) cells, contributing to lack of efficacy of current therapies. Integrin alpha4 (alpha4) mediates stromal adhesion of normal and malignant B-cell precursors, and according to gene expression analyses from 207 children with minimal residual disease, is highly associated with poorest outcome. We tested whether interference with alpha4-mediated stromal adhesion might be a new ALL treatment. Two models of leukemia were used, one genetic (conditional alpha4 ablation of BCR-ABL1 [p210(+)] leukemia) and one pharmacological (anti-functional alpha4 antibody treatment of primary ALL). Conditional deletion of alpha4 sensitized leukemia cell to nilotinib. Adhesion of primary pre-B ALL cells was alpha4-dependent; alpha4 blockade sensitized primary ALL cells toward chemotherapy. Chemotherapy combined with Natalizumab prolonged survival of NOD/SCID recipients of primary ALL, suggesting adjuvant alpha4 inhibition as a novel strategy for pre-B ALL.

Rapid thymic reconstitution following bone marrow transplantation in neonatal mice is VEGF-dependent.

Age-related differences in thymic function influence the rapidity of T cell reconstitution following hematopoietic stem cell transplantation (HSCT). In adults, thymic reconstitution is delayed until after marrow engraftment is established, and is significantly improved by approaches that increase marrow chimerism, such as pretransplantation irradiation. In contrast, we show that neonatal mice undergo more rapid and efficient thymic reconstitution than adults, even when bone marrow (BM) engraftment is minimal and in the absence of pretransplantation radiation. We have previously shown that the neonatal thymus produces high levels of vascular endothelial growth factor (VEGF) that drives angiogenesis locally. In this report, we show that inhibition of VEGF prior to HSCT prevents rapid thymic reconstitution in neonates, but has no effect on thymic reconstitution in adults. These data suggest that the early radiation-independent thymic reconstitution unique to the neonatal host is mediated through VEGF, and reveals a novel pathway that might be targeted to improve immune reconstitution post-HSCT.

Effects of sublethal irradiation on patterns of engraftment after murine bone marrow transplantation.

Attempts to reduce the toxicity of hematopoietic stem cell transplantation have led to the use of various immunosuppressive, yet nonmyeloablative preparative regimens that often include low-dose irradiation. To determine the effects of low-dose irradiation on the dynamics of donor cell engraftment after bone marrow transplantation (BMT), we coupled standard endpoint flow cytometric analysis with in vivo longitudinal bioluminescence imaging performed throughout the early (<10 days) and late (days 10-90) post-BMT periods. To exclude the contribution of irradiation on reducing immunologic rejection, severely immune-deficient mice were chosen as recipients of allogeneic bone marrow. Flow cytometric analysis showed that sublethal doses of total body irradiation (TBI) significantly increased long-term (14 weeks) donor chimerism in the bone marrow compared with nonirradiated recipients (P < .05). Bioluminescence imaging demonstrated that the effect of TBI (P < .001) on chimerism occurred only after the first 7 days post-BMT. Flow cytometric analysis on day 3 showed no increase in the number of donor cells in irradiated bone marrow, confirming that sublethal irradiation does not enhance marrow chimerism early after transplantation. Local irradiation also significantly increased late (but not early) donor chimerism in the irradiated limb. Intrafemoral injection of donor cells provided efficient early chimerism in the injected limb, but long-term systemic donor chimerism was highest with i.v. administration (P < .05). Overall, the combination of TBI and i.v. administration of donor cells provided the highest levels of long-term donor chimerism in the marrow space. These findings suggest that the major effect of sublethal irradiation is to enhance long-term donor chimerism by inducing proliferative signals after the initial phase of homing.

Predominant fusion of bone marrow-derived cardiomyocytes.

OBJECTIVES: Here we address the capacity of bone marrow-derived cells (BMDCs) to trans-differentiate into mature myocytes under the physiological stimulus of exercise training. METHODS: For this purpose, we have transplanted bone marrow from mice ubiquitously expressing enhanced green fluorescence protein (eGFP) into host mice that have been subjected to a prolonged program of exercise. RESULTS: In all successful bone marrow reconstitutions (greater than 80%), we observed rare but consistent events of bone marrow-derived cardiomyocytes, the frequency of which was unchanged upon exercise training. We have further determined whether these recruited myocytes are a product of trans-differentiation or fusion by the use of a genetic system that distinguishes cell fusion from trans-differentiation in a single-cell assay. CONCLUSIONS: We concluded that both in the unchallenged mouse and in the trained specimens, fusion is the most prominent mechanism by which bone marrow-derived cells are observed in the myocyte compartment.