Interventions for Persons with Mild Cognitive Impairment (MCI) An Evidence-Based Practice Project

This Evidence-Based Practice (EBP) project addressed the following question: What occupational therapy and multidisciplinary/interprofessional interventions are most effective for addressing mild cognitive impairment (MCI) to improve occupational performance, functional cognition, participation, well-being, quality of life, and caregiver burden

Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis _ state of the art

Fibrosis represents a major global disease burden, yet a potent antifibrotic compound is still not in sight. Part of the explanation for this situation is the difficulties that both academic laboratories and research and development departments in the pharmaceutical industry have been facing in re-enacting the fibrotic process in vitro for screening procedures prior to animal testing. Effective in vitro characterization of antifibrotic compounds has been hampered by cell culture settings that are lacking crucial cofactors or are not holistic representations of the biosynthetic and depositional pathway leading to the formation of an insoluble pericellular collagen matrix. In order to appreciate the task which in vitro screening of antifibrotics is up against, we will first review the fibrotic process by categorizing it into events that are upstream of collagen biosynthesis and the actual biosynthetic and depositional cascade of collagen I. We point out oversights such as the omission of vitamin C, a vital cofactor for the production of stable procollagen molecules, as well as the little known in vitro tardy procollagen processing by collagen C-proteinase/BMP-1, another reason for minimal collagen deposition in cell culture. We review current methods of cell culture and collagen quantitation vis-à-vis the high content options and requirements for normalization against cell number for meaningful data retrieval. Only when collagen has formed a fibrillar matrix that becomes cross-linked, invested with ligands, and can be remodelled and resorbed, the complete picture of fibrogenesis can be reflected in vitro. We show here how this can be achieved. A well thought-out in vitro fibrogenesis system represents the missing link between brute force chemical library screens and rational animal experimentation, thus providing both cost-effectiveness and streamlined procedures towards the development of better antifibrotic drugs

Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine

Idiopathic pulmonary fibrosis (IPF) is characterized by activation and injury of epithelial cells, the accumulation of connective tissue and changes in the inflammatory microenvironment. The bone morphogenetic protein (BMP) inhibitor protein gremlin-1 is associated with the progression of fibrosis both in human and mouse lung. We generated a transgenic mouse model expressing gremlin-1 in type II lung epithelial cells using the surfactant protein C (SPC) promoter and the Cre-LoxP system. Gremlin-1 protein expression was detected specifically in the lung after birth and did not result in any signs of respiratory insufficiency. Exposure to silicon dioxide resulted in reduced amounts of lymphocyte aggregates in transgenic lungs while no alteration in the fibrotic response was observed. Microarray gene expression profiling and analyses of bronchoalveolar lavage fluid cytokines indicated a reduced lymphocytic response and a downregulation of interferon-induced gene program. Consistent with reduced Th1 response, there was a downregulation of the mRNA and protein expression of the anti-fibrotic chemokine CXCL10, which has been linked to IPF. In human IPF patient samples we also established a strong negative correlation in the mRNA expression levels of gremlin-1 and CXCL10. Our results suggest that in addition to regulation of epithelial-mesenchymal crosstalk during tissue injury, gremlin-1 modulates inflammatory cell recruitment and anti-fibrotic chemokine production in the lung.Peer reviewe

Rapid thermal characterization of graphene oxide-nanocalorimetry as a pathway for novel insights in tribology

The use of solid lubricants such as graphene, graphene oxide, and other nanoparticles have gained notable attention in the tribological community to reduce friction and wear thus aiming at improved energy efficiency and sustainability. Tribological experiments unify rather extreme conditions such as high contact pressures, small contact areas, relative sliding motion, and rapid heating. This combination leads to mechanically- and/or thermally induced chemical, structural and microstructural modifications of the lubricating nanoparticles during rubbing thus altering their material’s properties. Due to the high sensitivity, we propose nanocalorimetry as the method of choice to shed more light on the thermally-induced processes and changes. As a model material for solid lubricants, we explore the transitions of graphene oxide under heating with 1000 °C/s up to 600 °C using quasi-adiabatic nanocalorimetry. We identify a strong exothermic runaway reaction at 317 °C. This runaway is preceded by exothermic reactions between 75–125 °C, which are correlated with the release of intercalated species and the formation of CO and CO$_{2}$

First-Principles Calculations of Thermoelectric Properties of IV–VI Chalcogenides 2D Materials

A first-principles study using density functional theory and Boltzmann transport theory has been performed to evaluate the thermoelectric (TE) properties of a series of single-layer 2D materials. The compounds studied are SnSe, SnS, GeS, GeSe, SnSe2, and SnS2, all of which belong to the IV–VI chalcogenides family. The first four compounds have orthorhombic crystal structures, and the last two have hexagonal crystal structures. Solving a semi-empirical Boltzmann transport model through the BoltzTraP software, we compute the electrical properties, including Seebeck coefficient, electrical conductivity, power factor, and the electronic thermal conductivity, at three doping levels corresponding to 300 K carrier concentrations of 1018, 1019, and 1020 cm−3. The spin orbit coupling effect on these properties is evaluated and is found not to influence the results significantly. First-principles lattice dynamics combined with the iterative solution of phonon Boltzmann transport equations are used to compute the lattice thermal conductivity of these materials. It is found that these materials have narrow band gaps in the range of 0.75–1.58 eV. Based on the highest values of figure-of-merit ZT of all the materials studied, we notice that the best TE material at the temperature range studied here (300–800 K) is SnSe