Supercooling: A Promising Technique for Prolonged Organ Preservation in Solid Organ Transplantation, and Early Perspectives in Vascularized Composite Allografts.

Ex-vivo preservation of transplanted organs is undergoing spectacular advances. Machine perfusion is now used in common practice for abdominal and thoracic organ transportation and preservation, and early results are in favor of substantially improved outcomes. It is based on decreasing ischemia-reperfusion phenomena by providing physiological or sub-physiological conditions until transplantation. Alternatively, supercooling techniques involving static preservation at negative temperatures while avoiding ice formation have shown encouraging results in solid organs. Here, the rationale is to decrease the organ's metabolism and need for oxygen and nutrients, allowing for extended preservation durations. The aim of this work is to review all advances of supercooling in transplantation, browsing the literature for each organ. A specific objective was also to study the initial evidence, the prospects, and potential applications of supercooling preservation in Vascularized Composite Allotransplantation (VCA). This complex entity needs a substantial effort to improve long-term outcomes, marked by chronic rejection. Improving preservation techniques is critical to ensure the favorable evolution of VCAs, and supercooling techniques could greatly participate in these advances

A LOFAR-IRAS cross-match study : the far-infrared radio correlation and the 150-MHz luminosity as a star-formation rate

13 pages, 13 figures, accepted for publication in A&A, © ESO 2019Aims. We aim to study the far-infrared radio correlation (FIRC) at 150 MHz in the local Universe (at a median redshift z~0:05) and improve the use of the rest-frame 150-MHz luminosity, L150, as a star-formation rate (SFR) tracer, which is unaffected by dust extinction. Methods. We cross-match the 60-um selected Revised IRAS Faint Source Survey Redshift (RIFSCz) catalogue and the 150-MHz selected LOFAR value-added source catalogue in the Hobby-Eberly Telescope Dark Energy Experiment (HETDEX) Spring Field. We estimate L150 for the cross-matched sources and compare it with the total infrared (IR) luminosity, LIR, and various SFR tracers. Results. We find a tight linear correlation between log L150 and log LIR for star-forming galaxies, with a slope of 1.37. The median qIR value (defined as the logarithm of the LIR to L150 ratio) and its rms scatter of our main sample are 2.14 and 0.34, respectively. We also find that log L150 correlates tightly with the logarithm of SFR derived from three different tracers, i.e., SFR_Halpha based on the Halpha line luminosity, SFR_60 based on the rest-frame 60-um luminosity and SFR_IR based on LIR, with a scatter of 0.3 dex. Our best-fit relations between L150 and these SFR tracers are, log L150 (Lsun) = 1.35(0.06) x log SFR_Halpha (Msun/yr) + 3.20(0.06), log L150 (Lsun) = 1.31(0.05) x log SFR_60 (Msun/yr) + 3.14(0.06), and log L150 (Lsun) = 1.37(0.05) x log SFR_IR (Msun/yr) + 3.09(0.05), which show excellent agreement with each other.Peer reviewedFinal Accepted Versio

Pathogenesis of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. The prevalence of NAFLD has risen rapidly in parallel with the dramatic rise in obesity and diabetes, and is rapidly becoming the most common cause of liver disease in Western countries. Indeed, NAFLD is now recognized to be the aetiology in many cases previously labelled as cryptogenic cirrhosis

Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines.

With increasing demand for donor organs for transplantation, machine perfusion (MP) promises to be a beneficial alternative preservation method for donor livers, particularly those considered to be of suboptimal quality, also known as extended criteria donor livers. Over the last decade, numerous studies researching MP of donor livers have been published and incredible advances have been made in both experimental and clinical research in this area. With numerous research groups working on MP, various techniques are being explored, often applying different nomenclature. The objective of this review is to catalog the differences observed in the nomenclature used in the current literature to denote various MP techniques and the manner in which methodology is reported. From this analysis, we propose a standardization of nomenclature on liver MP to maximize consistency and to enable reliable comparison and meta-analyses of studies. In addition, we propose a standardized set of guidelines for reporting the methodology of future studies on liver MP that will facilitate comparison as well as clinical implementation of liver MP procedures

Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization

The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of human acellular liver tissue cubes (ALTCs) using normal liver tissue unsuitable for transplantation. The application of high shear stress is a key methodological determinant accelerating the process of tissue decellularization while maintaining ECM protein composition, 3D-architecture and physico-chemical properties of the native tissue. ALTCs were engineered with human parenchymal and non-parenchymal liver cell lines (HepG2 and LX2 cells, respectively), human umbilical vein endothelial cells (HUVEC), as well as primary human hepatocytes and hepatic stellate cells. Both parenchymal and non-parenchymal liver cells grown in ALTCs exhibited markedly different gene expression when compared to standard 2D cell cultures. Remarkably, HUVEC cells naturally migrated in the ECM scaffold and spontaneously repopulated the lining of decellularized vessels. The metabolic function and protein synthesis of engineered liver scaffolds with human primary hepatocytes reseeded under dynamic conditions were maintained. These results provide a solid basis for the establishment of effective protocols aimed at recreating human liver tissue in vitro

Effectiveness and cost-effectiveness of self-help plus (sh+) for preventing mental disorders in refugees and asylum seekers in Europe and Turkey: Study protocols for two randomised controlled trials

Introduction This article describes two randomised controlled trials that will evaluate the effectiveness and cost-effectiveness of Self-Help Plus (SH+), a group self-help intervention developed by the WHO to reduce distress. In these trials SH+ is being tested as a preventative intervention to lower the incidence of mental disorders in asylum seekers and refugees with psychological distress resettled in Europe and Turkey. Methods and analysis Two prospective, multicentre, randomised, rater-blinded, parallel-group studies will follow participants over a period of 12 months. One trial will be conducted in Europe and one in Turkey. In each trial, 600 asylum seekers and refugees screening positive on the General Health Questionnaire (≥3), but without a formal diagnosis of any mental disorders according to the Mini International Neuropsychiatric Interview, will be randomly allocated to SH+or to enhanced treatment-as-usual. The primary outcome will be a lower incidence of mental disorders at 6 month follow-up. Secondary outcomes will include the evaluation of psychological symptoms, functioning, well-being, treatment acceptability and indicators of intervention cost-effectiveness. Ethics and dissemination The two trials received ethical clearance from the local Ethics Committees of the participating sites (seven sites), as well as from the WHO Ethics Committee. All participants will provide informed consent before screening and before study inclusion (a two-step procedure). The results of the trials will be disseminated in agreement with a dissemination plan that includes publication(s) in peer-reviewed journals and presentations at relevant national and international conferences and meetings. Trials registration numbers NCT03571347, NCT03587896

A ternary PEDOT-TiO2-reduced graphene oxide nanocomposite for supercapacitor applications

A ternary composite of PEDOT was prepared with TiO2 via emulsion polymerization method adjusting various weight ratios of TiO2 to PEDOT and synthesized rGO was then blended with this composite. The FTIR, UV–Vis and XRD analysis displayed characteristic features of PEDOT and TiO2. The morphology of the nano-hybrid structure was additionally investigated by SEM analysis. Pore size and surface area analysis of particles were characterized by BET method. The electrochemical analysis showed that the specific capacitance (Csp) for PEDOT-TiO2-15-rGO was 18.9 F.cm-2 at 0.1 mA g-1 current density

Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis

InForm software: A semi-Automated research tool to identify presumptive human hepatic progenitor cells, and other histological features of pathological significance

Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists' reports are the current gold-standard for assessment. However, it is often impractical to recruit pathologists in large cohort studies. In this study we utilise PerkinElmer's "InForm" software package to semi-Automate the scoring of patient liver biopsies, and compare outputs to a pathologist's assessment. We examined a cohort of eleven acute hepatitis samples and three non-Alcoholic fatty liver disease (NAFLD) samples, stained with HPC markers (GCTM-5 and Pan Cytokeratin), an inflammatory marker (CD45), Sirius Red to detect collagen and haematoxylin/eosin for general histology. InForm was configured to identify presumptive HPCs, CD45 +ve inflammatory cells, areas of necrosis, fat and collagen deposition (p < 0.0001). Hepatitis samples were then evaluated both by a pathologist using the Ishak-Knodell scoring system, and by InForm through customised algorithms. Necroinflammation as evaluated by a pathologist, correlated with InForm outputs (r 2 = 0.8192, p < 0.05). This study demonstrates that the InForm software package provides a useful tool for liver disease research, allowing rapid, and objective quantification of the presumptive HPCs and identifies histological features that assist with assessing liver disease severity, and potentially can facilitate diagnosis