Photocurable polymethacrylate-silica nanocomposites: correlation between dispersion stability, curing kinetics, morphology and properties

A comprehensive study of model systems based on poly(ethylene glycol) dimethacrylate and two methacryloxy-modified silicas (Aerosil R7200 and R711) were investigated to find possible correlation between the stability of the monomer/silica dispersion, curing kinetics, composite morphology and physical and mechanical properties of the final hybrid material. The monomer/silica dispersions were cured photochemically. The investigated parameters: Zeta potential, polymerization rate and conversion, glass transition, surface roughness and mechanical properties were found to be synchronous; when plotted as function of silica content, they showed maxima or changes in the trend at the same filler loading. This threshold (optimum) silica content in the composition was about 5 wt.-% for the investigated systems. The results obtained are discussed in terms of the solvation cell (which influences dispersion stability) and the interphase layer formation as well as their changes below and above of the threshold filler content

Human bone marrow mesenchymal stem cell-derived extracellular vesicles attenuate neuroinflammation evoked by focal brain injury in rats

Background Ischemic stroke is the major cause of long-term severe disability and death in aged population. Cell death in the infarcted region of the brain induces immune reaction leading to further progression of tissue damage. Immunomodulatory function of mesenchymal stem cells (MSCs) has been shown in multiple preclinical studies; however, it has not been successfully translated to a routine clinical practice due to logistical, economical, regulatory, and intellectual property obstacles. It has been recently demonstrated that therapeutic effect of intravenously administered MSCs can be recapitulated by extracellular vesicles (EVs) derived from them. However, in contrast to MSCs, EVs were not capable to decrease stroke-induced neuroinflammation. Therefore, the aim of the study was to investigate if intra-arterial delivery of MSC-derived EVs will have stronger impact on focal brain injury-induced neuroinflammation, which mimics ischemic stroke, and how it compares to MSCs. Methods The studies were performed in adult male Wistar rats with focal brain injury induced by injection of 1 mu l of 50 nmol ouabain into the right hemisphere. Two days after brain insult, 5 x 10(5) human bone marrow MSCs (hBM-MSCs) labeled with Molday ION or 1.3 x 10(9) EVs stained with PKH26 were intra-arterially injected into the right hemisphere under real-time MRI guidance. At days 1, 3, and 7 post-transplantation, the rats were decapitated, the brains were removed, and the presence of donor cells or EVs was analyzed. The cellular immune response in host brain was evaluated immunohistochemically, and humoral factors were measured by multiplex immunoassay. Results hBM-MSCs and EVs transplanted intra-arterially were observed in the rat ipsilateral hemisphere, near the ischemic region. Immunohistochemical analysis of brain tissue showed that injection of hBM-MSCs or EVs leads to the decrease of cell activation by ischemic injury, i.e., astrocytes, microglia, and infiltrating leucocytes, including T cytotoxic cells. Furthermore, we observed significant decrease of pro-inflammatory cytokines and chemokines after hBM-MSC or EV infusion comparing with non-treated rats with focal brain injury. Conclusions Intra-arterially injected EVs attenuated neuroinflammation evoked by focal brain injury, which mimics ischemic stroke, and this effect was comparable to intra-arterial hBM-MSC transplantation. Thus, intra-arterial injection of EVs might be an attractive therapeutic approach, which obviates MSC-related obstacles

Users’ processing of online marketplace listings for high and low involvement goods

Purpose: To understand how users of online marketplaces process market signals in their decision making and whether this depends on if the good is of high or low involvement. Design/methodology/approach: The paper employs a mixed methods approach. Study 1 draws on an analysis of interviews with online marketplace users using hypothetical eBay purchases as stimuli, understanding how users conceptualize specific market signals and whether their importance varies depending on the type of purchase (high versus low involvement good). Study 2 tests hypotheses derived from signaling theory, using an eye tracking experiment. Findings: Price and photographs act as “fast and frugal” signals for inclusion in consideration sets for low involvement purchases, but consumers deem them insufficient for high involvement purchases where high-cost signals that help establish seller credibility are far more salient. Users pay relatively greater attention to costly market signals, which are beyond sellers’ direct control, for high involvement goods. Practical implications: The paper offers insights for sellers regarding the presentation of quality cues and strategies online marketplaces can employ to reduce information asymmetry. Originality/value: Drawing on and extending signaling theory, the paper introduces and confirms hypotheses for understanding users’ attention to market signals when making purchase decisions on online marketplaces. It identifies how the degree of involvement of a product affects the processing of market signals

Natural Killer Cell Cytotoxicity and Immunosuppressive Cytokines (IL-10, TGF-β1) in Patients with Gastric Cancer

Cytotoxic activity of NK cells was estimated as related to IL-10 and TGF-β1 serum levels and Helicobacter pylori infection in gastric cancer patients. Moreover, we sought to determine whether human gastric adenocarcinoma cells in vitro release IL-10, TGF-β1 or factor(s) affecting NK cytotoxicity. The studies were conducted on 42 patients with gastric cancer (14 with I-II stage—group 1; 28 with III-IV stage—group 2) and on 20 healthy volunteers. The cytotoxicity was tested on NK cells isolated from peripheral blood. IL-10 and TGF-β1 levels were determined by ELISA. H. pylori was detected in cultures of gastric mucosa biopsies and in direct preparations. In 71.4% patients of group 1 NK cytotoxicity and IL-10 serum levels remained within a normal range while in 68% patients of group 2 a marked decrease was noted in cytotoxic function of NK cells, accompanied by increased levels of IL-10 in serum. In turn, in most patients of either group, independently of NK cytotoxicity and stage grouping in the patients, elevated serum levels of TGF-β1 were detected. Presence of H. pylori infection manifested no relationship with NK cytotoxicity, IL-10, or the TGF-β1 serum levels. In cultures of tumour cells presence of IL-10 and TGF-β1 was demonstrated. Nevertheless, supernatants of the cultures did not change cytotoxic activity of NK cells. Development of gastric carcinoma is accompanied by markedly decreased cytotoxic function of NK cells and by elevated IL-10 and TGF-β1 serum levels. Gastric carcinoma cells may release IL-10, the suppressive activity of which may in a secondary manner decrease NK cytotoxicity

Ultrastructural features of supraspinal muscles in rabbits after long-term transcutaneous lateral electrical surface stimulation (LESS)

Lateral electrical surface stimulation is one of methods used in the therapy of the progressive form of idiopathic scoliosis (IS) in children and youth. However, there are data suggesting that this method may lead to serious adverse side effects, when used for a too long period of time per day. To clarify this issue, the present study was aimed at disclosing possible changes in the ultrastructural appearance of rabbit supraspinal muscles undergoing long-term stimulation (9 h per day, 3 months), an animal model successfully used to mimic the situation in humans. In comparison to the control animals, muscles of "overstimulated" rabbits exhibited clear signs of microscopical lesions, including depletion and disintegration of myofilaments, proliferation, dilatation and, sometimes, swelling of sarcoplasmic reticulum and/or mitochondria, as well as signs of destruction of the Z line. The above-mentioned abnormalities, especially the signs of degenerative processes associated with the Z line and the observed microlesions strongly suggest that the failure of the long-term LESS therapy of the IS may be attributable to these ultrastructural lesions

Assessing externalizing and internalizing behaviour in children: use of the motor behaviour checklist in a typical school-age Polish sample

The study was designed to investigate externalizing and internalizing behaviours in a typical school-aged sample of children (N=112) using the Polish version of the Motor Behaviour Checklist for Children. The instrument was translated into Polish and teachers observed and recorded the motor behaviour of their students in school settings during physical education and free play situations. Findings demonstrated a psychometrically robust application of the MBC in a Polish sample as well as gender differences in total externalizing scores. In addition, age was found to be significant correlated with internalizing scores and especially with the social interaction factor. Teachers reported boys as more inattentive and more hyperactive/impulsive than girls and more likely to display externalising symptoms connected with ADHD particularly in school settings. Findings underscore the importance of early diagnosis and have practical implications when designing behavioural management programs and educational interventions in school settings

Evaluation of antimicrobial resistance of Helicobacter pylori in the last 15 years in West Poland

Increasing resistance to drugs represents a serious problem in treatment of infections with Helicobacter pylori, providing cause of frequent therapeutic failures. Present study aimed at analysis of changes in resistance of H. pylori to antibiotics in West Poland within the recent 15 years. 108 strains of H. pylori were analysed, isolated from gastric mucosa of adult patients. Group 1 involved 66 strains isolated in years of 1998/1999. Group 2 comprised 42 isolates obtained in years of 2013/2014. Susceptibility to amoxicillin (AMX), clarithromycin (CL), tetracycline (TC) and metronidazole (MTZ) was determined by E-test (AB Biodisc). All strains on both studied groups were susceptible to AMX. In group 1 all strains proved to be susceptible to TC, while 9% and 36% of tested strains were resistant to CL and MTZ, respectively. By contrast, in group 2, 31% and 83% of strains were resistant to CL and MTZ, respectively. In parallel, 14% strains were found to be resistant to TC (according to EUCAST interpretations). In West Poland, within recent 15 years a dramatic increase was noted in H. pylori strains resistant to metronidazole. In parallel, a significant increase was noted in proportion of strains resistant to clarithromycin

People with diabetes need a lower cut-off than others for depression screening with PHQ-9

Aims: This study evaluated the psychometric characteristics of the Polish version of the PHQ-9 in detecting major depression (MDD) and ‘MDD and/or dysthymia’ in people with and without type 2 diabetes. Methods: Participants were randomly selected from a diabetes outpatient facility (N = 216) and from among patients admitted to a medical center and psychiatric hospital (N = 99). The participants completed the PHQ-9. The Hamilton Depression Rating Scale and the Mini International Neuropsychiatric Interview were used to identify the presence of psychiatric symptoms. The optimal cut-offs for PHQ-9 in people with and without type 2 diabetes were investigated based on two methods: 1) Youden’s index which identifies cut-off points useful in scientific research; 2) a second method of two-stage screening for depressive disorders to provide guidance for clinical practice. Results: The Polish version of the PHQ-9 is a reliable and valid screening tool for depression in people with and without type 2 diabetes. An optimal cut-off of ≥ 7 was indicated by Youden’s index and ≥ 5 by the two-stage method for screening for MDD and ‘MDD and/or dysthymia’ in the group with type 2 diabetes. A cut-off of ≥ 11 was optimal for screening for both MDD and ‘MDD and/or dysthymia’ among people without diabetes (Youden’s index). The two-stage approach suggested a ≥ 10 score for screening for MDD and ≥ 9 for screening for ‘MDD and/or dysthymia’ in people without diabetes. Conclusions: A lower cut-off score of the PHQ-9 is recommended for people with type 2 diabetes as compared to the general population

Origins left, right and centre: increasing the number of initiation sites in the Escherichia coli chromosome

© 2018 by the authors. The bacterium Escherichia coli contains a single circular chromosome with a defined architecture. DNA replication initiates at a single origin called oriC. Two replication forks are assembled and proceed in opposite directions until they fuse in a specialised zone opposite the origin. This termination area is flanked by polar replication fork pause sites that allow forks to enter, but not to leave. Thus, the chromosome is divided into two replichores, each replicated by a single replication fork. Recently, we analysed the replication parameters in E. coli cells, in which an ectopic origin termed oriZ was integrated in the right-hand replichore. Two major obstacles to replication were identified: (1) head-on replication–transcription conflicts at highly transcribed rrn operons, and (2) the replication fork trap. Here, we describe replication parameters in cells with ectopic origins, termed oriX and oriY, integrated into the left-hand replichore, and a triple origin construct with oriX integrated in the left-hand and oriZ in the right-hand replichore. Our data again highlight both replication–transcription conflicts and the replication fork trap as important obstacles to DNA replication, and we describe a number of spontaneous large genomic rearrangements which successfully alleviate some of the problems arising from having an additional origin in an ectopic location. However, our data reveal additional factors that impact efficient chromosome duplication, highlighting the complexity of chromosomal architecture

The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends.

Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson's disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies