Subsynovial connective tissue development in the rabbit carpal tunnel

The carpal tunnel contains the digital flexor tendons and the median nerve, which are embedded in a unique network of fibrovascular interconnected subsynovial connective tissue (SSCT). Fibrous hypertrophy of the SSCT and subsequent adaptations in mechanical response are found in patients with carpal tunnel syndrome (CTS), but not much is known about the development of the SSCT. This observational study describes the morphological development of SSCT using histology and ultramicroscopy in an animal model at four time points between late-term fetuses through adulthood. A transition

Autocatalytic role of molecular hydrogen in copper-catalyzed transfer hydrogenation of ketones

Catalytic transfer hydrogenation of ketones and aldehydes is generally accepted to follow a dehydrogenation-hydrogenation mechanism on copper, which makes the increased hydrogenation rate and selectivity rather puzzling. Using first-principles microkinetics on a Cu(111) surface, we show that, rather than a dehydrogenation-hydrogenation mechanism, there is also direct proton transfer between the sacrificial alcohol and the reacting ketone. The ketone is hydrogenated to a stable alkoxy intermediate using surface hydrogen. This alkoxy intermediate is subsequently hydrogenated to the alcohol product via direct proton transfer from the sacrificial alcohol, also forming a sacrificial alkoxy intermediate. To close the catalytic cycle, the sacrificial alkoxy species dehydrogenates, forming its corresponding ketone. We also observed a surprising catalytic effect of molecular hydrogen, which can be explained by the rate-controlling step in transfer hydrogenation: the direct hydrogenation of the ketone to its alkoxy intermediate by surface hydrogen. Under all realistic reaction conditions, this step has the highest degree of rate control

Perfect-information games with lower-semicontinuous payoffs

We prove that every multiplayer perfect-information game with bounded and lower-semicontinuous payoffs admits a subgame-perfect epsilon-equilibrium in pure strategies. This result complements Example 3 in Solan and Vieille [Solan, E., N. Vieille. 2003. Deterministic multi-player Dynkin games. J. Math. Econom. 39 911-929], which shows that a subgame-perfect epsilon-equilibrium in pure strategies need not exist when the payoffs are not lower-semicontinuous. In addition, if the range of payoffs is finite, we characterize in the form of a Folk Theorem the set of all plays and payoffs that are induced by subgame-perfect 0-equilibria in pure strategies

Fame and future of faecal transplantations - developing next-generation therapies with synthetic microbiomes

Peer reviewe

Atmospheric pressure plasma and depositions of antibacterial coatings

Healthcare-associated infections (HCAI) are complications of healthcare that result in elevated patient morbidity and mortality. HCAI present a huge financial burden for patients, hospitals and insurers due to extended hospitalisation and associated care. According to the estimations, in the US alone, HCAI affects approximately 2 million patients annually, of whom approximately 90.000 patients die, with an estimated annual cost estimated to range from 28 billion to 45 billion US$. [1] European Union is facing the similar situation, the European Centre for Disease Prevention and control (ECDC) advice that approximately 4.1 million acute care patients acquire a HCAI annually, with 37.000 deaths directly attributed to HCAI. With increasing prevalence of HCAI across European countries and threatening development of antimicrobial resistance to widely used antibiotics, there is a recognised need for novel approach in battle against this healthcare burden [2]. One of the approaches involves a development and fabrication of materials with antimicrobial properties. Usually, these are coatings with integrated antibacterial agent that is responsible for the elimination of microorganisms that come into contact with active surface. There is a variety of different antibacterial compounds integrated in such coatings, such as different antibiotics, chemical compounds, peptides. Recently, metal nanoparticles (NPs) have been increasingly used in designing coatings with antibacterial properties due to their large surface-to-volume ration, physiochemical properties and biological multi-target mechanism of actions. Besides all beneficial properties of NPs their emergence of cytotoxicity is limiting their practical applications in human body. [3-4] To overcome this drawback it is important to design a new class of antibacterial coatings with firmly embedded NPs that allows controlled release of antimicrobial agent into the microenvironment. Atmospheric pressure plasma technology has shown a big promise as an alternative and cost-efficient method for deposition of coatings with antibacterial properties. This contribution explores the potential of plasma-assisted approach for fabrication of antibacterial coatings, containing different metal NPs on medical textiles. Plasma-assisted deposition of coatings was carried out with so-called ˝sandwich technique˝, where nanoparticles were embedded between two layers in order to tailor the desirable ion release and to prolong antibacterial effect of fabrics. Antibacterial effects of different nano-coatings were tested against G+ and G- bacterial species, Staphylococcus aureus and Escherichia coli, respectively. Besides antibacterial properties, potential cytotoxic effects were also studied. The study demonstrates that atmospheric pressure plasma can be an efficient technique for deposition of antibacterial coatings containing metal NPs. Medical textiles with plasma-assisted nano-coatings showed effective antibacterial properties. The choice of proper metal antimicrobial agent and optimal concentration of NPs should be considered in regards to potential cytotoxic effects when these materials would be used in medical environments.info:eu-repo/semantics/publishedVersio

Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy

Exome sequencing revealed a homozygous missense mutation (c.317C>G [p.Arg106Pro]) in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations (c.199_201del [p.G1n67del] and c.810+1G>T) in an unrelated person with cone-rod dystrophy. Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.G1n67del variant forms of POC1B. Morpholino-oligonucleotide-induced knockdown of poc1b translation in zebrafish resulted in a dose-dependent small-eye phenotype, impaired optokinetic responses, and decreased length of photoreceptor outer segments. These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs. Yeast two-hybrid screening of a human retinal cDNA library revealed FAM161A as a binary interaction partner of POC1B. This was confirmed in coimmunoprecipitation and colocalization assays, which both showed loss of FAM161A interaction with p.Arg106Pro and p.G1n67del variant forms of POC1B. FAM161A was previously implicated in autosomal-recessive retinitis pigmentosa and shown to be located at the base of the photoreceptor connecting cilium, where it interacts with several other ciliopathy-associated proteins. Altogether, this study demonstrates that POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors

Antibacterial nanocomposites based on Ag NPs and HMDSO deposited by atmospheric pressure plasma

The development of new multifunctional coatings with antimicrobial properties has a special interest in several applications for pharmaceutical and medical products. This work reports on the deposition of antimicrobial coatings based on silver nanoparticles (Ag NPs) embedded in an organosilicon film onto woven and nonwoven textiles. The Ag nanoparticles admixed with hexamethyldisiloxane (HMDSO) vapours are introduced by means of an atomizer system in the remote discharge of an atmospheric pressure plasma source operating in argon. The chemical properties and the surface morphology of the coatings with antimicrobial potential are discussed.This work was performed within the M-ERA-NET project PlasmaTex, contract 31/2016/ UEFISCDI. The financial support from the Ministry of Research and Innovation under the Nucleus contract 4N/2016 is gratefully acknowledged.info:eu-repo/semantics/publishedVersio

Control over imidazoquinoline immune stimulation by pH-degradable poly(norbornene) nanogels

The reactivation of the innate immune system by toll-like receptor (TLR) agonists holds promise for anticancer immunotherapy. Severe side effects caused by unspecific and systemic activation of the immune system upon intravenous injection prevent the use of small-molecule TLR agonists for such purposes. However, a covalent attachment of small-molecule imidazoquinoline (IMDQ) TLR7/8 agonists to pH-degradable polymeric nanogels could be shown to drastically reduce the systemic inflammation but retain the activity to tumoral tissues and their draining lymph nodes. Here, we introduce the synthesis of poly(norbornene)-based, acid-degradable nanogels for the covalent ligation of IMDQs. While the intact nanogels trigger sufficient TLR7/8 receptor stimulation, their degraded version of soluble, IMDQ-conjugated poly(norbornene) chains hardly activates TLR7/8. This renders their clinical safety profile, as degradation products are obtained, which would not only circumvent nanoparticle accumulation in the body but also provide nonactive, polymer-bound IMDQ species. Their immunologically silent behavior guarantees both spatial and temporal control over immune activity and, thus, holds promise for improved clinical applications

Double Dielectric Barrier (DBD) plasma-assisted deposition of chemical stabilized nanoparticles on polyamide 6,6 and polyester fabrics

The development of new multifunctional textiles containing nanoparticles (NPs) has had a special interest in several applications for pharmaceutical, medical, engineering, agricultural, and food products.[1-2] Cu, Zn and especially Ag NPs exhibit strong antibacterial activities on a broad spectrum of bacteria.[3-5] Most of the antimicrobial textiles coated with NPs are not able to perform a controlled release of the antibiotic species. Thus, the immobilization of NPs in the substrate or its inclusion in polymeric matrix is essential to control the NPs antibiotic effect with time. Dielectric barrier discharge (DBD) plasma technology is one of the most effective non-thermal plasma sources.[6] However, an even dispersion and coating of NPs onto fabrics remain a challenge due to the high degree of aggregation of metal NPs.[7] Some capping agents were described to increase the suspension stability such as citrate and SDS.[8] In this work, Ag, Zn, and Cu NPs deposition on DBD plasma pre-treated polyamide 6,6 (PA66) and polyester (PES) were tested for the production of durable antibacterial textiles. SEM-EDX analysis and the effect of some NPs stabilizers (e.g. sodium citrate, sodium alginate and Polyvinyl alcohol (PVA)) was analysed by dynamic light scattering (DLS) in term of size, polydispersity index and zeta potential. XPS analyses prove the DBD efficacy in providing oxygen species onto the fabric’s surfaces. The SEM analyses prove the deposition of the Ag and Cu NPs onto the PES and PA66 fabrics. No zinc was detected. However, antimicrobial tests in PES shows that all the NPs have an antimicrobial effect but Cu and Zn show activity only in S. aureus and Ag only in E.coli. Cu shows a reasonable dispersion onto the fibres but PVP coated AgNPs display a high level of aggregation even after 1 hour of ultrasonic treatment. To solve instability and aggregation problems, NPs suspensions were prepared in different concentrations (1, 2.5 and 5 wt%) of citrate, alginate and PVA using water and ethanol as control by ultrasonic bath. In table 1 are resumed the best results obtained for each NP compared to water as control. Ethanol and PVA were disregarded due to the highest instability and lowest ζ potential, respectively. XPS, SEM and antimicrobial data shows lack in coating uniformity. It is clear that doesn't exist a univocal dispersant and concentration for all NPs. Despite the improving in ζ potentials and stability of the colloids, the obtained sizes still show a high degree of aggregation.info:eu-repo/semantics/publishedVersio