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

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

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

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

Better use of data to improve parent satisfaction (BUDS): protocol for a prospective before-and-after pilot study employing mixed methods to improve parent experience of neonatal care

Introduction Having a baby that requires neonatal care is stressful and traumatic. Parents often report dissatisfaction with communication of clinical information. In the UK neonatal care data are recorded daily using electronic patient record systems (EPR), from which deidentified data form the National Neonatal Research Database (NNRD). We aim to evaluate the impact of sharing neonatal EPR data with parents, on parent-reported satisfaction, parent–staff interactions, staff workload and data completeness. Methods A prospective, before-and-after, mixed-method study. Participants are parents of inpatient babies (maximum 90) and staff in a tertiary neonatal intensive care unit, London, UK. The intervention was developed by former neonatal parents, neonatologists and neonatal nurses: a communication tool for parents comprising individualised, written, daily infant updates for parents, derived from EPR data. The intervention will be provided to parents over 6 weeks. Plan-Do-Study-Act cycles will inform the tool’s iterative development and improvement. The tool’s impact will be measured using a validated parent survey, staff survey, data completeness measures and interviews. Analysis Primary outcome: parent satisfaction ‘with communication of clinical information and involvement in care’. Secondary outcomes: parent–staff interactions, staff workload, data completeness. Baseline survey data will be obtained from clinical service evaluation preceding the intervention. Baseline data completeness will be derived from the NNRD. During the intervention, surveys will be administered biweekly and data completeness assessed daily. We will analyse outcomes using run charts and partially paired statistical tests. Parent and staff interviews will explore information exchange and the communication tool’s impact. Discussion This study will evaluate the impact of a parent co-designed intervention on communication with parents in neonatal care and the completeness of routinely recorded electronic clinical data. Better use of routinely recorded clinical data provides the opportunity to improve parent satisfaction and increase the research utility of such data, benefiting clinical care

UV-stable paper coated with APTES-modified P25 TiO2 nanoparticles

In order to inhibit the photocatalytic degradation of organic material supports induced by small titania (TiO2) nanoparticles, highly photocatalytically active, commercially available P25-TiO2 nanoparticles were first modified with a thin layer of (3-aminopropyl) triethoxysilane (APTES), which were then deposited and fixed onto the surface of paper samples via a simple, dip-coating process in water at room temperature. The resultant APTES-modified P25 TiO2 nanoparticle-coated paper samples exhibit much greater stability to UV-illumination than uncoated blank reference paper. Very little, or no, photo-degradation in terms of brightness and whiteness, respectively, of the P25-TiO2-nanoparticle-treated paper is observed. There are many other potential applications for this Green Chemistry approach to protect cellulosic fibres from UV-bleaching in sunlight and to protect their whiteness and maintain their brightness