Genetic Predisposition to Myelodysplastic Syndromes: A Challenge for Adult Hematologists

Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) differ in terms of prognosis and treatment strategy compared to MDS occurring in the adult population without an inherited genetic predisposition. The main molecular pathways affected in IBMFS involve telomere maintenance, DNA repair, biogenesis of ribosomes, control of proliferation and others. The increased knowledge on the genes involved in MDS pathogenesis and the wider availability of molecular diagnostic assessment have led to an improvement in the detection of IBMFS genetic predisposition in MDS patients. A punctual recognition of these disorders implies a strict surveillance of the patient in order to detect early signs of progression and promptly offer allogeneic hematopoietic stem cell transplantation, which is the only curative treatment. Moreover, identifying an inherited mutation allows the screening and counseling of family members and directs the choice of donors in case of need for transplantation. Here we provide an overview of the most recent data on MDS with genetic predisposition highlighting the main steps of the diagnostic and therapeutic management. In order to highlight the pitfalls of detecting IBMFS in adults, we report the case of a 27-year-old man affected by MDS with an underlying telomeropathy.     

3D Bioprinting of Human Adipose-Derived Stem Cells and Their Tenogenic Differentiation in Clinical-Grade Medium

Defining the best combination of cells and biomaterials is a key challenge for the development of tendon tissue engineering (TE) strategies. Adipose-derived stem cells (ASCs) are ideal candidates for this purpose. In addition, controlled cell-based products adherent to good manufacturing practice (GMP) are required for their clinical scale-up. With this aim, in this study, ASC 3D bioprinting and GMP-compliant tenogenic differentiation were investigated. In detail, primary human ASCs were embedded within a nanofibrillar-cellulose/alginate bioink and 3D-bioprinted into multi-layered square-grid matrices. Bioink viscoelastic properties and scaffold ultrastructural morphology were analyzed by rheology and scanning electron microscopy (SEM). The optimal cell concentration for printing among 3, 6 and 9 × 10⁶ ASC/mL was evaluated in terms of cell viability. ASC morphology was characterized by SEM and F-actin immunostaining. Tenogenic differentiation ability was then evaluated in terms of cell viability, morphology and expression of scleraxis and collagen type III by biochemical induction using BMP-12, TGF-β3, CTGF and ascorbic acid supplementation (TENO). Pro-inflammatory cytokine release was also assessed. Bioprinted ASCs showed high viability and survival and exhibited a tenocyte-like phenotype after biochemical induction, with no inflammatory response to the bioink. In conclusion, we report a first proof of concept for the clinical scale-up of ASC 3D bioprinting for tendon TE.     

Indoor air quality in schools of a highly polluted south Mediterranean area

This study aimed at surveying lower secondary schools in southern Italy, in a highly polluted area. A community close to an industrial area and three villages in rural areas was investigated. Indoor temperature, relative humidity (RH), gaseous pollutants (CO₂ and NO₂), selected biological pollutants in indoor dust, and the indoor/outdoor mass concentration and elemental composition of PM_2.5 were ascertained. Temperature and RH were within, or close to, the comfort range, while CO₂ frequently exceeded the threshold of 1000 ppm, indicating inadequate air exchange rate. In all the classrooms, median NO₂ levels were above the WHO threshold value. Dermatophagoides p. allergen concentration was below the sensitizing threshold, while high endotoxin levels were detected in the classrooms, suggesting schools may produce significant risks of endotoxin exposure. Concentration and solubility of PM_2.5 elements were used to identify the sources of indoor particles. Indoor concentration of most elements was higher than outdoors. Resuspension was responsible for the indoor increase in soil components. For elements from industrial emission (Cd, Co, Ni, Pb, Sb, Tl, V), the indoor concentration depended on penetration from the outside. For these elements, differences in rural vs industrial concentrations were found, suggesting industrial sources may influence indoor air quality nearby schools.     

Evaluating an automated mediator for joint narratives in a conflict situation

ABSTRACT

Joint narratives are often used in the context of reconciliation interventions for people in social conflict situations, which arise, for example, due to ethnic or religious differences. The interventions aim to encourage a change in attitudes of the participants towards each other. Typically, a human mediator is fundamental for achieving a successful intervention. In this work, we present an automated approach to support remote interactions between pairs of participants as they contribute to a shared story in their own language. A key component is an automated cognitive tutor that guides the participants through a controlled escalation/de-escalation process during the development of a joint narrative. We performed a controlled study comparing a trained human mediator to the automated mediator. The results demonstrate that an automated mediator, although simple at this stage, effectively supports interactions and helps to achieve positive outcomes comparable to those attained by the trained human mediator.     

Natural resources derived biocomposites as potential carriers of green pesticides in agricultural field: Designing and fabrication of a pot-like device

Hemp fibers (HF) are used as filler in pectin to produce biocomposites. To improve the compatibility of the filler with the polymeric matrix, HF are treated through mechanochemically assisted alkaline attack. The effect of the treatment time on the morphology of HF is investigated through atomic force microscopy and infrared spectroscopy. Cinnamic acid, a green pesticide, is added to the composites in order to test the capability of such materials to act as potential devices in the agricultural field. Analysis of thermal, mechanical, barrier properties and surface energy are evaluated on biocomposites and compared either to unfilled pectin or to composites filled with untreated HF. The release of cinnamic acid is evaluated and found to be dependent on the fibers' treatment time. The design and the fabrication of a pot prototype is also reported. The manufacture appears promising as green functional container for plants to be implanted in the ground.     

Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury

The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.     

Design guidelines of CMOS class-AB output stages: a tutorial

This article presents useful guidelines for designing CMOS class-AB output stages. Three Quality Factors, which allow analysis and comparison of different output stages, are used to design two CMOS class-AB stages. We show that using the proposed Quality Factors and the related strategy leads to an efficient design in terms trade-off among area, current consumption, bandwidth and distortion. Indeed, for one of the two stages adopted as example, the design through the Quality Factors results in superior distortion performance with respect to the design suggested in the original article. Design examples and simulations are provided to validate the design strategy.     

Temperature Effect on Concrete Creep Modeled by Microprestress-Solidification Theory

The previously developed microprestress-solidification theory for concrete creep and shrinkage is generalized for the effect of temperature (not exceeding 100°C). The solidification model separates the viscoelasticity of the solid constituent, the cement gel, from the chemical aging of material caused by solidification of cement and characterized by the growth of volume fraction of hydration products. This permits considering the viscoelastic constituent as non-aging. The temperature dependence of the rates of creep and of volume growth is characterized by two transformed time variables based on the activation energies of hydration and creep. The concept of microprestress achieves a grand unification of theory in which the long-term aging and all transient hygrothermal effects simply become different consequences of one and the same physical phenomenon. The microprestress, which is independent of the applied load, is initially produced by incompatible volume changes in the microstructure during hydration, and later builds up when changes of moisture content and temperature create a thermodynamic imbalance between the chemical potentials of vapor and adsorbed water in the nanopores of cement gel. As recently shown, this simultaneously captures two basic effects: First, the creep decreases with increasing age at loading after the growth of the volume fraction of hydrated cement has ceased; and, second, the drying creep, i.e., the transient creep increases due to drying (Pickett effect) which overpowers the effect of steady-state moisture content (i.e., less moisture—less creep). Now it is demonstrated that the microprestress buildup and relaxation also captures a third effect: The transitional thermal creep, i.e., the transient creep increase due to temperature change. For computations, an efficient (exponential-type) integration algorithm is developed. Finite element simulations, in which the apparent creep due to microcracking is taken into account separately, are used to identify the constitutive parameters and a satisfactory agreement with typical test data is achieved.     

A software development system based on a macroprocessor

In this paper a system for software development is described. This system consists of a general-purpose macroprocessor and a set of service programs. The macroprocessor has been planned to work in a conversational environment and to this purpose a set of utilities has been inserted to aid the editing and the debugging of the macrodefinitions. Indeed the system allows the user to select, by means of commands, the flow of the operations to be executed and to choose when and how any program has to be expanded. The macroprocessor is easy to use and it is suitable to generate codes for both high-level languages and assembler languages.     

Artificial neural network for the second virial coefficient of organic and inorganic compounds: An ANN for B of organic and inorganic compounds

An artificial neural network (ANN) to estimate the second virial coefficient, valid for organic and inorganic compounds, is presented. First, we statistically analyzed 6,531 experimental points, belonging to 234 fluids, collected from literature. The data were investigated with a factor analysis approach to identify the most significant parameters that influence the second virial coefficient. The factor analysis, combined with physical considerations, allowed to find four (T_r, T_c, P_c, ω) or five (μ_r) parameters as input variables for the ANN, according to the specific chemical family. The architecture of the proposed multi-layers perceptron (MLP) neural network consists of one input layer with five input variables (T_r, T_c, P_c, ω, μ_r), one output layer with one neuron (B) and two-hidden-layers with 19 neurons each. We trained, validated and tested several configurations of the neural network to obtain this network topology that minimizes the deviations between experimental and calculated points. Results show that the ANN is able to calculate the second virial coefficient with greater accuracy (RMSE?=?29.38?cm³/mol) than that of correlations available in literature. To identify the outliers and applicability domain of the proposed MLP neural network, an outlier diagnosis based on the Leverage approach was performed. This analysis shows that the model is statistically valid.