Successful Control of Acute Myelofibrosis with Lenalidomide

Acute panmyelosis with myelofibrosis (APMF) is a rare, fatal hematological neoplasm that is characterized by the acute onset of cytopenias and fibrosis in the bone marrow in the absence of splenomegaly or fibrosis-related morphological changes in the RBCs. We present the case of a 59-year-old female who presented with a two-month history of anemia, leucopenia and a normal platelet count. The marrow was heavily fibrotic, and no aspirate material could be obtained; the biopsy showed extensive infiltration with small to medium size megakaryocytes, dysplastic changes in the erythroid compartment, and left shift in the myeloid cells. The patient was treated for four months with anabolic steroids (Danazol), growth factors and received regular blood transfusions. At 4 months after diagnosis, the patient was started on Lenalidomide, 10 mg/day for a 21-d-course along with growth factor support. At 6 months after treatment, the patient was transfusion-independent, had normalized blood counts, and, at 32 months on continuous lenalidomide treatment, her needs for growth factor support have been minimized. Repeat bone marrow biopsies showed a patchy distribution of fibrosis with areas of normal cellularity and morphology. To our knowledge, this is the first case for a medication that could reverse the fatal outcome of APMF

EDIN Scale Implemented by Gestational Age for Pain Assessment in Preterms : A Prospective Study

Background. Chronic neonatal pain can lead to long-term adverse effects on the immature brain. EDIN scale for prolonged pain might not be fully suitable for premature infants. We aimed to test a modified EDIN scale, adding postmenstrual age (PMA) as a sixth item (EDIN6). Methods. In a two-phase prospective study, pain was assessed in all neonates admitted in our NICU. In T1 EDIN was applied; in T2 EDIN6 with additional scores of 2, 1, and 0, respectively, for 25-32, 33-37, and >37 weeks PCA was tested. Scores > 6 suggested pain. The nursing staff was given a questionnaire to evaluate EDIN and EDIN6. Results. A total of 15960 pain assessments were recorded (8693 in T1; 7267 in T2). With EDIN6, cumulative detection of pain almost tripled (117/7267 versus 52/8693, p=0.001). Main differences were found among less mature categories (50/1472 versus 17/1734, p=0.001 in PCA 25-32; 26/2606 versus 10/4335, p=0.001 in PMA 33-37; 41/3189 versus 25/2624, p=0.26 in PMA > 37). Adequacy of pain assessment in lower PMA was judged "medium-high" in 13,4% of nurses in T1 and 71,4% in T2. Conclusions. EDIN6 may allow improved evaluation of pain in preterm infants

Zymographic assay of plant diamine oxidase on entrapped peroxidase polyacrylamide gel electrophoresis. A study of stability to proteolysis

A zymographic assay of diamine oxidase (DAO, histaminase, EC 1.4.3.6), based on a coupled peroxidase reaction, and its behavior at proteolysis in simulated gastric and intestinal conditions, are described. The DAO activity from a vegetal extract of Lathyrus sativus seedlings was directly determined on sodium dodecyl sulfate polyacrylamide electrophoretic gels containing entrapped horseradish peroxidase, with putrescine as substrate of histaminase and ortho-phenylenediamine as co-substrate of peroxidase. The accumulation of azo-aniline, as peroxidase-catalyzed oxidation product, led to well-defined yellow-brown bands on gels, with intensities corresponding to the enzymatic activity of DAO. After image analysis of gels, a linear dependency of DAO content (Coomassie-stained protein bands) and of its enzymatic activity (zymographic bands) with the concentration of the vegetal extract was obtained. In simulated gastric conditions (pH 1.2, 37 °C), the DAO from the vegetal extract lost its enzymatic activity before 15 min of incubation, either in the presence or absence of pepsin. The protein pattern (Coomassie-stained) revealed that the DAO content from the vegetal extract was kept almost constant in the simulated intestinal fluid (containing pancreatin or not), with a slight diminution in the presence of pancreatic proteases. After 10 h of incubation at 37 °C, the DAO enzymatic activity from the vegetal extract was 44.7% in media without pancreatin and 13.6% in the presence of pancreatin, whereas the purified DAO retained only 4.65% of its initial enzymatic activity in the presence of pancreatin

Arsenic Trioxide Enhances the Radiation Sensitivity of Androgen-Dependent and -Independent Human Prostate Cancer Cells

Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells) and PC-3 cells (androgen-independent human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with arsenic trioxide (ATO) and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS) generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer

correction to unpacking configurational dynamics sequence analysis and qualitative comparative analysis as a mixed method design

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Urbanismo y desplobaciòn en Italia

La despoblación de las regiones periféricas ciertamente no es un tema nuevo; sin embargo, las formas y modalidades con las que el fenómeno ha adquirido relevancia jurídica han variado profundamente a lo largo del tiempo. Históricamente, las medidas de lucha más drásticas tuvieron lugar durante el Régimen fascista que, adoptando una clara estrategia de lucha contra las migraciones internas, definió un minucioso sistema de control a cargo de determinados actores institucionales. De hecho, ya con la Ley n.o 358 de 9 de abril de 1931, se instituyó la figura del Comisariado para las Migraciones, al que fue encomendada la tarea de autorizar los desplazamientos territoriales. Con la Ley n.o 1092 de 6 de julio de 1939, se adoptaron las medidas contra la urbanización, cuya disposición más significativa fue la prohibición del traslado a ciudades con población superior a veinticinco mil habitantes, si no estaba justificado por motivos de trabajo u otros perfectamente acreditados , y la repatriación forzosa con intervención policial al ayuntamiento de origen para los transgresores. Sin embargo, se ha mantenido constante una cierta interconexión entre este fenómeno y la normativa urbanística; tanto es así que la atención hacia la ola de flujos migratorios del campo a las ciudades, en un cierto sentido, se puede considerar consubstancial a la urbanística moderna como doctrina de estudio autónoma. En este sentido, parece emblemática ya de principio la formulación del art. 1 de la Ley n.o 1150 de 17 de agosto de 1942, cuando atribuye al entonces Ministerio de Obras Públicas la supervisión de la actividad urbanística también con el fin de garantizar, en la renovación y ampliación arquitectónica de las ciudades, «el respeto de las características tradicionales, favorecer la desurbanización y frenar la tendencia a la urbanización»

A Mixed-Method Impact Evaluation Design of a Mobile Phone Application for Nutrition Service Delivery in Indonesia

Child undernutrition remains one of the most devastating realities in many parts of the world. The use of mobile phone technology may offer innovative opportunities to tackle persistently high levels of child undernutrition. Despite the enthusiasm for using mobile phones for nutrition service delivery, a recent review found very few studies that critically assessed their application. A major shortcoming of the existing studies was that they were all based on small one-off pilot projects and integration into national nutrition strategies or programmes was minimal or non-existent. As a result of this lack of integration, the sustainability of mobile phone-based nutrition systems was generally low and most projects ceased to exist after the pilot. Together with World Vision Indonesia and World Vision Canada, we aim to address this evidence gap. We set out to rigorously evaluate the piloting of a mobile phone application for nutrition service delivery, including community-based growth monitoring and nutrition counselling.UK Department for International Developmen