Therapeutic Potential of Exosomes Derived from Adipose Tissue-Sourced Mesenchymal Stem Cells in the Treatment of Neural and Retinal Diseases

Therapeutic agents that are able to prevent or attenuate inflammation and ischemia-induced injury of neural and retinal cells could be used for the treatment of neural and retinal diseases. Exosomes derived from adipose tissue-sourced mesenchymal stem cells (AT-MSC-Exos) are extracellular vesicles that contain neurotrophins, immunoregulatory and angio-modulatory factors secreted by their parental cells. AT-MSC-Exos are enriched with bioactive molecules (microRNAs (miRNAs), enzymes, cytokines, chemokines, immunoregulatory, trophic, and growth factors), that alleviate inflammation and promote the survival of injured cells in neural and retinal tissues. Due to the nano-sized dimension and bilayer lipid envelope, AT-MSC-Exos easily bypass blood–brain and blood–retinal barriers and deliver their cargo directly into the target cells. Accordingly, a large number of experimental studies demonstrated the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases. By delivering neurotrophins, AT-MSC-Exos prevent apoptosis of injured neurons and retinal cells and promote neuritogenesis. AT-MSC-Exos alleviate inflammation in the injured brain, spinal cord, and retinas by delivering immunoregulatory factors in immune cells, suppressing their inflammatory properties. AT-MSC-Exos may act as biological mediators that deliver pro-angiogenic miRNAs in endothelial cells, enabling re-vascularization of ischemic neural and retinal tissues. Herewith, we summarized current knowledge about molecular mechanisms which were responsible for the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases, emphasizing their therapeutic potential in neurology and ophthalmology.     

Historical changes in hydrology,geomorphology, and floodplain vegetation of the Willamette River,Oregon

Historical trends in hydrology, geomorphology, and floodplain vegetation provide fundamental contexts for designing future management of large rivers, an area of fluvial research extensively informed by studies of historical channel dynamics. Changes in hydrology, channel structure, floodplain forests, and large wood were documented for the 273‐km main stem of the Willamette River from 1850 to present. Reduced sediment supply and frequency and magnitude of floods have decreased channel mobility and incised channels, leading to fewer gravel bars, islands, and side channels. Human alteration of channel morphology, vegetation, and bank hardening has exacerbated channel simplification caused by reductions in floods, sediment supply, and inputs of wood. A substantial number of floodplain channels reoccupied remnants of previous active channels inundated during recent floods, demonstrating functional but often forgotten role of historical geomorphic structure in modern floodplains and flood processes. In most reaches, area of floodplain forests in 1990 was only 10% to 25% of the area of forests in 1850. Abundance of wood in the wetted channel was generally greater in reaches with higher abundances of floodplain forests. Future trajectories will be influenced by legacies of the historical river but increasingly will reflect evolution of a new river shaped by human development, changing climate, and emerging hydrogeomorphic and vegetation processes. Understanding historical characteristics and anticipating future rates and patterns of ecosystem change provide fundamental contexts for restoring biophysical processes and structure in a large floodplain river.     

Particulate emission rates for unpaved shoulders along a paved road

OBJECTIVE: To study the effect of agricultural change and subsequent social change on the nutritional situation of 4 communities of different regions and climates, that since the 70's have changed from traditional corn production to commercial sorghum production. MATERIAL AND METHODS: A new dietetic and clinical survey (1996) was performed to follow-up the changes in the 4 communities studied 12 years before (1984). RESULTS: The food consumption pattern continued changing, with more dietary diversification, better protein quality and less corn consumption. The child nutrition status on average was better. This happened in spite of the fact that the sorghum production was in a crisis and the communities partially returned to corn production, diversified production or migrated from the communities. CONCLUSIONS: In spite of first abandoning traditional corn production and later having problems with the commercial product (sorghum), the communities are still improving their nutrition. This is mostly due to implementing certain survival strategies, to receiving support from the people from the community who migrated and to a better food availability.     

Prior episodes of sodium depletion increase the need-free sodium intake of the rat.

Prior episodes of sodium depletion increase the daily 3% NaCl intake of rats. They ingest large volumes and continue to do so for as long as 3 months after recovery from sodium deficit while eating sodium-rich food and while plasma sodium concentration and renal function are normal. The increased daily intake of sodium is, therefore, need-free. There is a marked sex difference in the need-free intake of 3% NaCl. Female rats drink more salt than do male rats when they are sodium replete and depletion naive. Repeated depletions raise the need-free intakes of both sexes but the effect is greater in females. Plasma concentrations of angiotensin II and aldosterone, which are markedly elevated by each episode of sodium depletion, return to basal levels between and after depletions, and are not the cause of the chronically increased need-free salt intake of the multi-depleted rat. These results suggest that the persistent increase in daily 3% NaCl intake that occurs in the rat with a history of repeated sodium depletions is a permanent, nonpathological increase in avidity for the taste of salty substances that results in life-long overconsumption of salt. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessment of psychopathy in a population of incarcerated adolescent offenders.

The reliability, validity, and factor structure of a modified version of the Psychopathy Checklist—Revised (PCL—R) for adolescents was investigated, completed using file information only, in a sample of incarcerated Black and White male adolescents. Interrater reliability and internal consistency were high, and confirmatory factor analyses and coefficients of congruence showed that the factor structure in this sample resembled the 2-factor solution found in adults. No significant racial differences were found for reliability or mean PCL—R scores. In addition, relationships between PCL—R scores and psychometric measures and behavioral indicators of maladjustment were similar to those previously found in adult populations. The construct of psychopathy, as defined by the PCL—R modified for use with adolescents, appears applicable to both Black and White adolescent male offenders. The study gives evidence for the structural and substantive validity of the modified PCL—R in this population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.     

Effect of drug loading on the properties of temperature‐responsive polyester–poly(ethylene glycol)–polyester hydrogels

Hydrogels that can undergo gelation upon injection in vivo are promising systems for the site‐specific delivery of drugs. In particular, some thermo‐responsive gels require no chemical additives but simply gel in response to a change from a lower temperature to physiological temperature (37 °C). The gelation mechanism does not involve covalent bonds, and it is possible that incorporation of drugs into the hydrogel could disrupt gelation. We investigated the incorporation of drugs into thermo‐responsive hydrogels based on poly(?‐caprolactone‐co‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(?‐caprolactone‐co‐lactide) (PCLA–PEG–PCLA). Significant differences in properties and in the response to incorporation of the anti‐inflammatory drug celecoxib (CXB) were observed as the PEG block length was varied from 1500 to 3000 g mol^?1. Linear viscoelastic moduli of a PCLA–PEG–PCLA hydrogel containing a 2000 g mol^?1 PEG block were least affected by the incorporation of CXB and this gel also exhibited the slowest release of CXB, so the incorporation of phenylbutazone, methotrexate, ibuprofen, diclofenac and etodolac was also investigated for this hydrogel. Different drugs resulted in varying degrees of syneresis of the hydrogels, suggesting that they interact with the polymer networks in different ways. In addition, the drugs had varying effects on the viscoelastic and compressive moduli of the gels. The results showed that the effects of drug loading on the properties of thermo‐responsive hydrogels can be substantial and depend on the drug. For applications such as intra‐articular drug delivery, in which the mechanical properties of the hydrogel are important, these effects should thus be studied on a case‐by‐case basis. © 2019 Society of Chemical Industry     

Green Roof Hydrological Modelling With GRU and LSTM Networks

Green Roofs (GRs) are increasing in popularity due to their ability to manage roof runoff while providing a number of additional ecosystem services. Improvement of hydrological models for the simulation of GRs will aid design of individual roofs as well as city scale planning that relies on the predicted impacts of widespread GR implementation. Machine learning (ML) has exploded in popularity in recent years, however there are no studies focusing on the use of ML in hydrological simulation of GRs. We focus on two types of ML-based model: long short-term memory (LSTM) and gated recurrent unit (GRU), in modelling GRs hydrological performance, with sequence input andsingle output (SISO), and synced sequence input and output (SSIO) architectures. Results of this paper indicate that both LSTM and GRU are useful tools for GR modelling. As the time window length (memory length, time step length of input data) increases, SISO appears to have a higher overall forecast accuracy. SSIO delivers the best overall performance, when the SSIO is close to, or even exceeds, the maximum window size.

     

Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation

Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8; MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001; Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001; Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required.