Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients

[Background aims] In allogeneic stem cell transplantation, unrelated donors are chosen in cases where appropriate related donors are not available. Peripheral blood stem cells (PBSCs) are more often selected as a graft source than bone marrow (BM). However, the prognostic benefits of PBSCs versus BM transplants from unrelated donors have not been carefully examined in patients with acute myeloid leukemia (AML). This study compared outcomes of adult AML patients who underwent unrelated PBSC and BM transplantation, evaluating post-transplant complications, including engraftment, graft-versus-host disease (GVHD) and infections, and determined subgroups of patients who are most likely to benefit from unrelated PBSCs compared with BM transplants. [Methods] The authors analyzed 2962 adult AML patients who underwent unrelated PBSC or BM transplants between 2011 and 2018 (221 PBSC and 2741 BM) using the Japanese nationwide registry database, in which graft source selection is not skewed toward PBSCs. [Results] In 49.7% of patients, disease status at transplantation was first complete remission (CR1). In 57.1% of cases, HLA-matched donors were selected. Myeloablative conditioning was performed in 75.1% of cases, and anti-thymocyte globulin (ATG) was added to conditioning in 10.5%. Multivariate analyses showed a trend toward favorable non-relapse mortality (NRM) in PBSC recipients compared with BM recipients (hazard ratio [HR], 0.731, P = 0.096), whereas overall survival (OS) (HR, 0.959, P = 0.230) and disease-free survival (DFS) (HR, 0.868, P = 0.221) were comparable between PBSC and BM recipients. Although the rate of chronic GVHD (cGVHD) was significantly higher in PBSC patients (HR, 1.367, P = 0.016), NRM was not increased, mainly as a result of significantly reduced risk of bacterial infections (HR, 0.618, P = 0.010), reflecting more prompt engraftments in PBSC recipients. Subgroup analyses revealed that PBSC transplantation was advantageous in patients transplanted at CR1 and in those without ATG use. PBSC recipients experienced significantly better OS and/or DFS compared with BM recipients in this patient group. [Conclusions] The authors' results confirmed the overall safety of unrelated PBSC transplantation for adult AML patients and suggested an advantage of PBSCs, especially for those in CR1. Further optimization of the prophylactic strategy for cGVHD is required to improve the overall outcome in transplantation from unrelated PBSC donors

Deconstructing the traditional Japanese medicine “Kampo”: compounds, metabolites and pharmacological profile of maoto, a remedy for flu-like symptoms

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1β, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism

Cell motion predicts human epidermal stemness

Image-based identification of cultured stem cells and noninvasive evaluation of their proliferative capacity advance cell therapy and stem cell research. Here we demonstrate that human keratinocyte stem cells can be identified in situ by analyzing cell motion during their cultivation. Modeling experiments suggested that the clonal type of cultured human clonogenic keratinocytes can be efficiently determined by analysis of early cell movement. Image analysis experiments demonstrated that keratinocyte stem cells indeed display a unique rotational movement that can be identified as early as the two-cell stage colony. We also demonstrate that α6 integrin is required for both rotational and collective cell motion. Our experiments provide, for the first time, strong evidence that cell motion and epidermal stemness are linked. We conclude that early identification of human keratinocyte stem cells by image analysis of cell movement is a valid parameter for quality control of cultured keratinocytes for transplantation

Palladium-Catalyzed Germylation of Aryl Bromides and Aryl Triflates Using Hexamethyldigermane

Palladium-catalyzed germylation of aryl bromides and aryl triflates using commercially available hexamethyldigermane is described. Optimized reaction conditions afforded various functionalized aryltrimethylgermanes, including drug-like molecules, in moderate to good yields, demonstrating the versatility of the presented protocols

Proposal for improvement of production process in a company that produces PVC fittings through thermoforming using dmaic improvement cycle

TesisEn el presente trabajo se plantea reducir las mermas de producción de un fabricante que elabora accesorios de tubería PVC aplicando como herramienta el ciclo de mejora DMAIC. Se desarrollarán las fases Definir (D), Medir (M), Analizar (A), Mejorar (I) y Controlar (C) con el soporte de herramientas estadísticas en cada una de dichas fases. Para el diagnóstico de la situación actual de la empresa se empleó las 3 primeras fases del ciclo de mejora DMAIC: Definir, Medir y Analizar. En la fase Definir, se identificó al problema principal mediante una matriz que considera factores diversos como frecuencia, pérdidas mensuales y facilidad para su implementación. De esta manera, se selecciona como problema principal la alta merma que tiene la empresa. Asimismo, se establecen los alcances del proyecto mediante el Proyect charter. En la fase Medir, se describe la situación actual de la empresa en la que trabaja. Se evalúa el impacto económico por la merma de producción que se tiene y se clasifica los productos por familias identificándose aquellas de mayor participación. Se realiza el análisis del VSM para visualizar las características de cada uno de los subprocesos identificados. Para realizar el análisis de capacidad del proceso, se tomó una muestra representativa y luego se calculó dichos indicadores. En la fase Analizar, se realizó el diagrama causa efecto para identificar las posibles causas al problema. Se llevó de la información cualitativa a la cuantitativa mediante un gráfico de Pareto y se plantearon hipótesis de correlación entre el tiempo y la temperatura. Para la evaluación de la propuesta de mejora, se utilizó la fase Mejorar de la metodología LSS. En la fase Mejorar, se realizaron propuestas para los procesos del corte y termoformado. Para el proceso de corte se planteó la utilización de soportes, sujetadores laterales y una cuchilla de corte vertical. Todo lo mencionado anteriormente va junto a un procedimiento. En el proceso del termoformado, se propuso el uso de un horno refractario y un sistema de control del flujo de gas automatizado para la medición correcta de la temperatura. Para la evaluación de los resultados, se empleó la fase Controlar de la metodología LSS. En la fase Controlar, se realizó un prototipo de horno refractario y se realizó pruebas para poder obtener el tiempo cuando empieza a ganar flexibilidad si se trabaja con la temperatura VICAT (80 °C). Se obtuvo un tiempo de 23 segundos en promedio. Se tomó una muestra con las secciones utilizadas en la prueba para verificar el nuevo índice de capacidad. La información recopilada sirvió para simular como trabaja la mejora en el tiempo y mediante el software Arena comprobar la efectividad de la mejora. Se estima reducir del 12% al 6%, con lo que se logra cumplir el objetivo principal del proyecto. El análisis financiero indica que la inversión si es rentable en el tiempo luego de realizada la propuesta de mejora por lo que se debería de realizar la implementació