Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-β, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.     

Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2

Erythropoietin (EPO) downregulates hepcidin expression to increase the availability of iron; the downregulation of hepcidin is mediated by erythroferrone (ERFE) secreted by erythroblasts. Erythroblasts also express transferrin receptor 2 (TFR2); however, the possible role of TFR2 in hepcidin downregulation is unclear. The purpose of the study was to correlate liver expression of hepcidin with the expression of ERFE and TFR2 in murine bone marrow and spleen at 4, 16, 24, 48, 72 and 96 h following administration of a single dose of EPO. Splenic Fam132b expression increased 4 h after EPO injection; liver hepcidin mRNA was decreased at 16 h. In the spleen, expression of TFR2 and transferrin receptor (TFR1) proteins increased by an order of magnitude at 48 and 72 h after EPO treatment. The EPO-induced increase in splenic TFR2 and TFR1 was associated with an increase in the number of Tfr2- and Tfr1-expressing erythroblasts. Plasma exosomes prepared from EPO-treated mice displayed increased amount of TFR1 protein; however, no exosomal TFR2 was detected. Overall, the results confirm the importance of ERFE in stress erythropoiesis, support the role of TFR2 in erythroid cell development, and highlight possible differences in the removal of TFR2 and TFR1 from erythroid cell membranes.     

In Situ Hydroxyapatite Synthesis Enhances Biocompatibility of PVA/HA Hydrogels

Bone tissue engineering tries to simulate natural behavior of hard tissues. This study aimed to produce scaffolds based on polyvinyl alcohol (PVA) and hyaluronic acid (HA) with hydroxyapatite (HAp) incorporated in two different ways, by in situ synthesis and physical mixing of pre-prepared HAp. In situ synthesis resulted in calcium deficient form of HAp with lower crystallinity. The proliferation of human osteoblast-like cells MG-63 proved to be better in the scaffolds with in situ synthesized HAp compared to those with physically mixed pre-prepared HAp. For scaffolds with PVA/HA/HAp ratio 3:1:2, there was significantly higher initial adhesion (p = 0.0440), as well as the proliferation in the following days (p < 0.001). It seemed to be advantageous improve the properties of the scaffold by in situ synthesizing of HAp directly in the organic matrix.     

Serum concentrations of neutral and phenolic organohalogens in pregnant women and some of their infants in The Netherlands

As part of a large European Union (EU)-funded comparative toxicology and human epidemiology study, EU-Compare, a selection of organohalogen compounds (OHCs) was analyzed in maternal serum, collected at the 35th week of pregnancy, and in cord serum of a number of their infants to determine maternal concentrations and to investigate the extent of transplacental transfer of these compounds. Eight neutral OHCs were analyzed: one polychlorinated biphenyl (PCB: CB-153),4,4'-DDE, five polybrominated diphenyl ethers (PBDEs: BDE-47, BDE-99, BDE-100, BDE-153, and BDE-154), and hexabromocyclododecane (HBCDD). Five phenolic OHCs were analyzed: three hydroxylated PCBs (40H-CB-107, 40H-CB-146, and 40H-CB-187), one hydroxylated PBDE (60H-BDE-47), and pentachlorophenol (PCP). All OHCs, except 60H-BDE-47, were present in maternal and cord serum. The historically identified OHCs showed the highest concentration: 4,4'-DDE (median value 89 ng/g lipid in maternal serum and 68 ng/g lipid in cord serum) and PCP (median value 970 pg/g serum in maternal serum and 1500 pg/g serum in cord serum). HBCDD and the PBDEs were present at much lower concentrations. We conclude that OHCs are present in the serum of pregnant women, and all compounds tested are transferred over the placenta. Because transfer is occurring at a critical stage of infant development, investigation of the health impact is urgent.     

Thermoelastic study of a functionally graded annular fin with variable thermal parameters using semiexact solution

Abstract

In this paper, the thermoelastic behavior of a functionally graded material (FGM) annular fin is investigated. The material properties of the annular fin are assumed to vary radially. The heat transfer coefficient and internal heat generation are considered to be functions of temperature. A closed form solution of nonlinear heat transfer equation for the FGM fin is obtained using the homotopy perturbation method (HPM) which leads to nonuniform temperature distributions within the fin. The temperature field is then coupled with the classical theory of elasticity and the associated thermal stresses are derived analytically. For the correctness of the present closed form solution for the stress field, the results are compared with the ANSYS-based finite element method (FEM) solution. The present HPM-based closed form solution of the stress field exhibits a good agreement with the FEM results. The effect of various thermal parameters such as the thermogeometric parameter, conduction-radiation parameter, internal heat generation parameter, coefficient of variation of thermal conductivity, and the coefficient of thermal expansion on the thermal stresses are discussed. The results are presented in both nondimensional and dimensional form. The dimensional stress analysis discloses the suitability of FGM as the fin material in practical applications.     

Groundwater-surface water interactions and agricultural nutrient transport in a Great Lakes clay plain system

Nutrient export from agricultural land to surface waters is a significant environmental concern within the Great Lakes Basin (GLB). A field-based watershed-scale study was completed to investigate spatial and temporal variations of phosphorus and nitrate to assess nutrient transport pathways and groundwater-surface water interactions in an agriculturally dominated clay plain system. This was conducted in the 127 km² Upper Parkhill Watershed, near Lake Huron in southwestern Ontario, Canada. Data collection occurred from June 2018 to May 2019 via continuous sensor deployment and discrete sampling of stream water, groundwater, hyporheic zone, and tile drainage water. Samples were analyzed for various nutrient species (total, total dissolved, soluble reactive, and particulate phosphorus, and nitrate-N) to examine the hydrological dynamics of principal transport pathways of agriculturally-derived nutrients. Total phosphorus and nitrate concentrations in stream water ranged from 0.007 to 0.324 mg/L and 0.32 to 13.13 mg NO₃^?-N/L, respectively. Tile drainage water total phosphorous concentrations varied from 0.006 to 0.066 mg/L. Groundwater total dissolved phosphorus concentrations ranged from <0.003 to 0.085 mg/L. Transport of phosphorus through tile drainage was observed to be greater than through groundwater over the study period. No distinct relationship was observed between nutrient concentrations in the hyporheic zone and the vertical hydraulic gradient within this zone in the studied stream reach. Preliminary correlations were discerned between water quality observations and recognized land management practices. Given the elevated stream nutrient concentrations, these results are consequential for the continual improvement of strategies and programs devised to conserve water resources within the GLB.     

Chlorinated phenols in human milk

The paper deals with the contamination of human milk with chlorinated phenols. The average and median concentrations of the chlorophenols investigated ranged from 0.75 to 9.74 g.kg^–1 and from being not detectable to 5.62 g.kg^–1, respectively, for the different compounds. The highest average and median levels were found for pentachlorophenol and 2,4,5-trichlorophenol. The concentrations determined were below the permissible levels.     

3D-FE-Analysis of CT-specimens including viscoplastic material behavior and nonlocal damage

In order to describe the time-dependent inelastic behavior of steel structures up to failure, a material model is developed within the framework of thermodynamics considering viscoplastic material behavior, isotropic hardening, softening, and isotropic ductile damage. Since softening and damage lead to localization of deformations, the model is extended by a non-local implicit gradient formulation. An additional gradient equation is formulated for the local damage variable in order to achieve results independent of the finite-element discretization. The approach is verified by 3D-structural analysis of CT-specimens.     

Sound Velocity of Kaolin in the Temperature Range from 20 °C to 1100 °C

The sound velocity of Sedlec kaolin during heating from 20 °C to 1100 °C was investigated by modulated force thermomechanical analysis (mf-TMA). In the interval from 20 °C to 250 °C, the sound velocity increases which can be explained by liberation of the water molecules from pores and micropores. Dehydroxylation (450 °C to 650 °C) presents itself with a decrease of the sound velocity. After dehydroxylation, a two-step increase of the sound velocity was observed. The first step of the increase of the sound velocity is due to solid-state sintering at low temperatures. The second step starts at 950 °C as a consequence of the collapse of the metakaolinite structure. After the maximum, a steep increase of the sound velocity follows as a result of solid-state sintering.