136 research outputs found

    Nano-biocomposite films with modified cellulose nanocrystals and synthesized silver nanoparticles

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    Ternary nano-biocomposite films based on poly(lactic acid) (PLA) with modified cellulose nanocrystals (s-CNC) and synthesized silver nanoparticles (Ag) have been prepared and characterized. The functionalization of the CNC surface with an acid phosphate ester of ethoxylated nonylphenol favoured its dispersion in the PLA matrix. The positive effects of the addition of cellulose and silver on the PLA barrier properties were confirmed by reductions in the water permeability (WVP) and oxygen transmission rate (OTR) of the films tested. The migration level of all nano-biocomposites in contact with food simulants were below the permitted limits in both non-polar and polar simulants. PLA nano-biocomposites showed a significant antibacterial activity influenced by the Ag content, while composting tests showed that the materials were visibly disintegrated after 15 days with the ternary systems showing the highest rate of disintegration under composting conditions.L.V. would like to acknowledge the financial support from MIUR, PRIN 2010–11 project entitled “Nanomed” (prot.2010FPTBSH 009). M.P. and A.J. acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness (MAT2011-28648-C02-1)

    Mutations in the Cardiac Ryanodine Receptor Gene (hRyR2) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia

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    BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is a genetic arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. The electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with calcium overload and the delayed afterdepolarizations observed during digitalis toxicity. We speculated that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease; therefore, we considered the human cardiac ryanodine receptor gene (hRyR2) a likely candidate for this genetically transmitted arrhythmic disorder. METHODS AND RESULTS: Twelve patients presenting with typical catecholaminergic polymorphic ventricular tachycardia in the absence of structural heart abnormalities were identified. DNA was extracted from peripheral blood lymphocytes, and single-strand conformation polymorphism analysis was performed on polymerase chain reaction-amplified exons of the hRyR2 gene. Four single nucleotide substitutions leading to missense mutations were identified in 4 probands affected by the disease. Genetic analysis of the asymptomatic parents revealed that 3 probands carried de novo mutations. In 1 case, the identical twin of the proband died suddenly after having suffered syncopal episodes. The fourth mutation was identified in the proband, in 4 clinically affected family members, and in none of 3 nonaffected family members in a kindred with 2 sudden deaths that occurred at 16 and 14 years, respectively, in the sisters of the proband. CONCLUSIONS: We demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia

    A new calculation of atmospheric neutrino flux: the FLUKA approach.

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    Abstract Preliminary results from a full 3-D calculation of atmospheric neutrino fluxes using the FLUKA interaction model are presented and compared to previous existing calculations. This effort is motivated mainly by the 3-D capability and the satisfactory degree of accuracy of the hadron-nucleus models embedded in the FLUKA code. Here we show examples of benchmarking tests of the model with cosmic ray experiment results. A comparison of our calculation of the atmospheric neutrino flux with that of the Bartol group, for E ν > 1 GeV, is presented

    Growing Role of 3D In Vitro Cell Cultures in the Study of Cellular and Molecular Mechanisms: Short Focus on Breast Cancer, Endometriosis, Liver and Infectious Diseases

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    Over the past decade, the development of three-dimensional (3D) models has increased exponentially, facilitating the unravelling of fundamental and essential cellular mechanisms by which cells communicate with each other, assemble into tissues and organs and respond to biochemical and biophysical stimuli under both physiological and pathological conditions. This section presents a concise overview of the most recent updates on the significant contribution of different types of 3D cell cultures including spheroids, organoids and organ-on-chip and bio-printed tissues in advancing our understanding of cellular and molecular mechanisms. The case studies presented include the 3D cultures of breast cancer (BC), endometriosis, the liver microenvironment and infections. In BC, the establishment of 3D culture models has permitted the visualization of the role of cancer-associated fibroblasts in the delivery of exosomes, as well as the significance of the physical properties of the extracellular matrix in promoting cell proliferation and invasion. This approach has also become a valuable tool in gaining insight into general and specific mechanisms of drug resistance. Given the considerable heterogeneity of endometriosis, 3D models offer a more accurate representation of the in vivo microenvironment, thereby facilitating the identification and translation of novel targeted therapeutic strategies. The advantages provided by 3D models of the hepatic environment, in conjunction with the high throughput characterizing various platforms, have enabled the elucidation of complex molecular mechanisms underlying various threatening hepatic diseases. A limited number of 3D models for gut and skin infections have been developed. However, a more profound comprehension of the spatial and temporal interactions between microbes, the host and their environment may facilitate the advancement of in vitro, ex vivo and in vivo disease models. Additionally, it may pave the way for the development of novel therapeutic approaches in diverse research fields. The interested reader will also find concluding remarks on the challenges and prospects of using 3D cell cultures for discovering cellular and molecular mechanisms in the research areas covered in this review

    Hep3Gel: A Shape-Shifting Extracellular Matrix-Based, Three-Dimensional Liver Model Adaptable to Different Culture Systems

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    Drug-induced hepatotoxicity is a leading cause of clinical trial withdrawal. Therefore, in vitro modeling the hepatic behavior and functionalities is not only crucial to better understand physiological and pathological processes but also to support drug development with reliable high-throughput platforms. Different physiological and pathological models are currently under development and are commonly implemented both within platforms for standard 2D cultures and within tailor-made chambers. This paper introduces Hep3Gel: a hybrid alginate-extracellular matrix (ECM) hydrogel to produce 3D in vitro models of the liver, aiming to reproduce the hepatic chemomechanical niche, with the possibility of adapting its shape to different manufacturing techniques. The ECM, extracted and powdered from porcine livers by a specifically set-up procedure, preserved its crucial biological macromolecules and was embedded within alginate hydrogels prior to crosslinking. The viscoelastic behavior of Hep3Gel was tuned, reproducing the properties of a physiological organ, according to the available knowledge about hepatic biomechanics. By finely tuning the crosslinking kinetics of Hep3Gel, its dualistic nature can be exploited either by self-spreading or adapting its shape to different culture supports or retaining the imposed fiber shape during an extrusion-based 3D-bioprinting process, thus being a shape-shifter hydrogel. The self-spreading ability of Hep3Gel was characterized by combining empirical and numerical procedures, while its use as a bioink was experimentally characterized through rheological a priori printability evaluations and 3D printing tests. The effect of the addition of the ECM was evident after 4 days, doubling the survival rate of cells embedded within control hydrogels. This study represents a proof of concept of the applicability of Hep3Gel as a tool to develop 3D in vitro models of the liver

    Implementation of the WHO standards to assess quality of care for children with acute pain in EDs: findings of a multicentre study (CHOICE) in Italy

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    Background: There is little experience on the use of the WHO Standards for improving the quality of care (QOC) for children. We describe the use of four prioritised WHO Standard-based Quality Measures to assess the provision of care for children with pain in emergency departments (EDs). Methods: In a multicentre observational study in 10 EDs with different characteristics in Italy, we collected data on 3355 children accessing the EDs between January 2019 and December 2020. The association between children and facility characteristics and quality measures was analysed through multivariate analyses. Results: The proportion of children whose pain was measured was 68.7% (n=2305), with extreme variations across different centres (from 0.0% to 99.8%, p<0.001). The proportion of children treated for pain was 28.9% (n=970) again with a wide range (5.3%-56.3%, p<0.001). The difference between the frequency of children with pain measured and pain treated varied widely between the facilities (ranging from -24.3 to 82). Children with moderate and severe pain were more frequently treated (48.9% and 62.9% of cases, respectively), although with large variations across centres (ranges: 0%-74.8% and 0%-100% respectively, p<0.001). After correction for children's characteristics, the variable more strongly associated with analysed outcomes was the facility which the child accessed for care. Being a facility in Northern Italy was associated with a higher rate of pain measurement (67.3%-95% CI: 39.9% to 94.6%, p<0.001) compared with facilities in South Italy (-22.1% lower (95% CI: -41.7% to -2.50%, p=0.03). Conclusions: The use of few WHO Standard-based measures related to pain can help identifying priority gaps in QOC for children and in monitoring it over time. There is a need for more implementation research to establish which are the most sustainable and effective interventions to improve the QOC for acute pain in children
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