A rare case of acute lymphoblastic leukemia in a patient with light chain (AL) amyloidosis treated with lenalidomide.

Lenalidomide belongs to a novel class of drugs called Immunomodulators which are now being used for the treatment of plasma cell dyscrasias with variable degrees of efficacy and toxicity. Though Second Primary Malignancies (SPM) have been a concern with its use, the benefits of the treatment outweigh the risks. The leukemogenic risk seems to be potentiated especially when combined with alkylating agents and the SPMs documented are predominantly myeloblastic. To date there are no reported cases of new lymphocytic leukemias in AL amyloidosis, regardless of whether undergone treatment or not. We present a case of AL amylodosis who was treated with lenalidomide and subsequently developed acute lymphoblastic leukemia

Intelligent agents & interoperable simulation for strategic decision making on multicoalition joint operations

This paper proposes an innovative interoperable federation developed for addressing strategic decision making on multi-coalition operations. The proposed architecture integrates several different simulators in HLA and is open to be operated in different modes from stand alone basic installation to fully integrated with entity based simulations. The simulator uses Intelligent Agents, to reproduce human behavior and human factors, as well as discrete event simulation paradigm into virtual and constructive environments. The paper describes the models as well as the approach to address this problem; some experimental results related a realistic scenario are proposed as well as the different a solutions adopted to support Commander engagement in using this kind of simulation

Validation of numerical approaches for electromagnetic characterization of magnetic resonance radiofrequency coils

Numerical methods based on solutions of Maxwell's equations are usually adopted for the electromagnetic characterization of Magnetic Resonance (MR) Radiofrequency (RF) coils. In this context, many different numerical methods can be employed, including time domain methods, e.g., the Finite-Difference Time-Domain (FDTD), and frequency domain methods, e.g., the Finite Element Methods (FEM) and the Method of Moments (MoM). We provide a quantitative comparison of performances and a detailed evaluation of advantages and limitations of the aforementioned methods in the context of RF coil design for MR applications. Specifically, we analyzed three RF coils which are representative of current geometries for clinical applications: a 1.5 T proton surface coil; a 7T dual tuned surface coil; a 7T proton volume coil. The numerical simulation results have been compared with measurements, with excellent agreement in almost every case. However, the three methods differ in terms of required computing resources (memory and simulation time) as well as their ability to handle a realistic phantom model. For this reason, this work could provide "a guide to select the most suitable method for each specific research and clinical applications at low and high field"

Measuring functional ability in healthy ageing: a nationwide cross-sectional survey in the Philippine older population

OBJECTIVES: To analyse the empirical support of the functional ability concept in the healthy ageing framework developed by the WHO in a sample of the Philippine older population. According to this framework, environmental factors may enhance or hinder functional ability, which is the person's ability to do what they value, broadly represented by subjective well-being. Moreover, this network of relationships may be moderated by personal characteristics such as gender. DESIGN: Cross-sectional observational study. SETTING: Philippines, general population. PARTICIPANTS: Respondents of the 2016 National Disability Prevalence Survey/Model Functioning Survey aged 50+ (N=2825). PRIMARY AND SECONDARY OUTCOME MEASURES: Latent (unobserved) measures of functional ability, environmental factors (physical environmental factors and social network and support) and subjective well-being (positive affect, negative affect and evaluative well-being) were obtained from different items from the survey questionnaire using a SEM framework. RESULTS: We found that the relationship between environmental factors and the three components of subjective well-being considered in this study was partially explained by differences in functional ability. The portion of those effects accounted for by functional ability was comparatively larger for the physical than for the social environmental factors. We found no evidences of gender differences in this network of relationships. CONCLUSIONS: These findings suggest the relevance of functional ability at explaining the relationship between environmental factors and subjective well-being in older adults. Future studies may replicate these findings longitudinally and including other relevant measures as the person's objective level of intrinsic capacity

Analysis of the gene expression profile of mouse male meiotic germ cells

Wide genome analysis of difference in gene expression between spermatogonial populations from 7-day-old mice and pachytene spermatocytes from 18-day-old mice was performed using Affymetrix gene chips representing approximately 12,500 mouse known genes or EST sequences, spanning approximately 1/3rd of the mouse genome. To delineate differences in the profile of gene expression between mitotic and meiotic stages of male germ cell differentiation, expressed genes were grouped in functional clusters. The analysis confirmed the previously described pre-meiotic or meiotic expression for several genes, in particular for those involved in the regulation of the mitotic and meiotic cell cycle, and for those whose transcripts are accumulated during the meiotic stages to be translated later in post-meiotic stages. Differential expression of several additional genes was discovered. In few cases (pro-apoptotic factors Bak, Bad and Bax), data were in conflict with the previously published stage-dependent expression of genes already known to be expressed in male germ cells. Northern blot analysis of selected genes confirmed the results obtained with the microarray chips. Six of these were novel genes specifically expressed in pachytene spermatocytes: a chromatin remodeling factor (chrac1/YCL1), a homeobox gene (hmx1), a novel G-coupled receptor for an unknown ligand (Gpr19), a glycoprotein of the intestinal epithelium (mucin 3), a novel RAS activator (Ranbp9), and the A630056B21Rik gene (predicted to encode a novel zinc finger protein). These studies will help to delineate the global patterns of gene expression characterizing male germ cell differentiation for a better understanding of regulation of spermatogenesis in mammals

Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads

A library of hybrid molecules is developed based on the common chemical features shared by clemastine and tamoxifen both of which are well known for their antileishmanial activities. In the initial screening against Leishmania major and L. amazonensis promastigotes, as well as cytotoxicity assays using HepG2 cells, several hybrids showed submicromolar activity against the parasite and no toxicity against human cells. The compounds with an EC50 10 were further characterized against intracellular amastigotes as well as promastigotes of species that cause both visceral and cutaneous leishmaniasis, such as L. infantum and L. braziliensis, respectively. These sequential screenings revealed the high pan-activity of this class of molecules against these species, with several compounds displaying an EC50 ≤ 2 μM against both promastigotes and intracellular amastigotes. Two of them were identified as the potential templates for lead optimization of this series having shown the highest activities against all species in both stages of parasite. The present findings can serve as a good starting point in the search for novel antileishmanial compounds that are easy to access and highly active