[Radiotherapy Indications in Patients with Hematological Malignancies During the Five Years Course of Modernized Center of Oncology and Radiotherapy Clinic in Pilsen]. / Indikace radioterapie u pacientu s hematologickými malignitami v prubehu peti let provozu modernizovaného centra Onkologické a radioterapeutické kliniky v Plzni.

Submitted: 27. 2. 2016.

Speciation and lability of Ag-, AgCl-, and Ag2S-nanoparticles in soil determined by X-ray absorption spectroscopy and diffusive gradients in thin films.

Long-term speciation and lability of silver (Ag-), silver chloride (AgCl-), and silver sulfide nanoparticles (Ag2S-NPs) in soil were studied by X-ray absorption spectroscopy (XAS), and newly developed "nano" Diffusive Gradients in Thin Films (DGT) devices. These nano-DGT devices were designed specifically to avoid confounding effects when measuring element lability in the presence of nanoparticles. The aging profile and stabilities of the three nanoparticles and AgNO3 (ionic Ag) in soil were examined at three different soil pH values over a period of up to 7 months. Transformation of ionic Ag, Ag-NP and AgCl-NPs were dependent on pH. AgCl formation and persistence was observed under acidic conditions, whereas sulfur-bound forms of Ag dominated in neutral to alkaline soils. Ag2S-NPs were found to be very stable under all conditions tested and remained sulfur bound after 7 months of incubation. Ag lability was characteristically low in soils containing Ag2S-NPs. Other forms of Ag were linked to higher DGT-determined lability, and this varied as a function of aging and related speciation changes as determined by XAS. These results clearly indicate that Ag2S-NPs, which are the most environmentally relevant form of Ag that enter soils, are chemically stable and have profoundly low Ag lability over extended periods. This may minimize the long-term risks of Ag toxicity in the soil environment.

Modulation of Macrophages Differentiation by Nanoscale-Engineered Geometric and Chemical Features.

Macrophage differentiation into M1 (inflammatory) and M2 (healing) phenotypes plays a vital role in determining the fate of biomaterials. The biophysical properties of the extracellular matrix are known to affect macrophage behavior. Mimicking these special biophysical properties of the extracellular matrix has led to increasing interest in biomaterial constructs with tailor-engineered surface nanotopographical and chemical properties. However, a significant gap of knowledge exists in the role played by the combinational effect of surface nanotopography and chemistry. To address this gap, we have fabricated nanoporous surfaces of controlled pore size (30, 65, and 200 nm) and lateral spacing with uniform outermost surface chemistry tailored with amines (NH2), carboxyl (COOH-) and hydrocarbon (CH3-) functionalities. We show that the combinatory effects of surface properties can direct the differentiation of macrophages to the pro-healing M2 phenotype. This is most evident on the surface featuring nanopores of 200 nm and -COOH functionality. Overall, the concentration of pro-inflammatory cytokines significantly decreases, while the concentration of anti-inflammatory cytokines increases many folds on nanotopographically, and chemically, modified surfaces compared to their planar counterparts. Our data provide pioneering knowledge that could provide pathways to tuning inflammatory and foreign body responses and instruct the design of tailor-engineered biomaterial implants to enable better clinical outcomes.

Preparation of gold nanoparticles in an aqueous medium using 2-mercaptosuccinic acid as both reduction and capping agent.

Monolayer protected gold nanoparticles with diameters above 10 nm were prepared by a simple, one step reaction in water. 2-mercaptosuccinic acid (MSA) was used both as reduction agent for hydrogen tetrachloroaurate (HAuCl4) and as stabilizing agent for the gold nanoparticles. Size distribution and surface chemistry were investigated by UV-Vis spectroscopy, scanning electron microscopy and Fourier Transform Infrared Spectroscopy. Particle size can be controlled by adjusting the molar portions of the reactants. The resulting particles are efficiently stabilized against aggregation when MSA is used in a concentration of 40% and above. Below a minimum MSA concentration a long-term particle growth is observed.

Correction: Rapid fabrication of functionalised poly(dimethylsiloxane) microwells for cell aggregate formation.

Correction for 'Rapid fabrication of functionalised poly(dimethylsiloxane) microwells for cell aggregate formation' by A. Forget et al., Biomater. Sci., 2017, 5, 828-836.

Rapid fabrication of functionalised poly(dimethylsiloxane) microwells for cell aggregate formation.

Cell aggregates reproduce many features of the natural architecture of functional tissues, and have therefore become an important in vitro model of tissue function. In this study, we present an efficient and rapid method for the fabrication of site specific functionalised poly(dimethylsiloxane) (PDMS) microwell arrays that promote the formation of insulin-producing beta cell (MIN6) aggregates. Microwells were prepared using an ice templating technique whereby aqueous droplets were frozen on a surface and PDMS was cast on top to form a replica. By employing an aqueous alkali hydroxide solution, we demonstrate exclusive etching and functionalisation of the microwell inner surface, thereby allowing the selective absorption of biological factors within the microwells. Additionally, by manipulating surface wettability of the substrate through plasma polymer coating, the shape and profile of the microwells could be tailored. Microwells coated with antifouling Pluronic 123, bovine serum albumin, collagen type IV or insulin growth factor 2 were employed to investigate the formation and stability of MIN6 aggregates in microwells of different shapes. MIN6 aggregates formed with this technique retained insulin expression. These results demonstrate the potential of this platform for the rapid screening of biological factors influencing the formation and response of insulin-producing cell aggregates without the need for expensive micromachining techniques.

CATALOGIC 301C model - validation and improvement.

In Europe, REACH legislation encourages the use of alternative in silico methods such as (Q)SAR models. According to the recent progress of Chemical Substances Control Law (CSCL) in Japan, (Q)SAR predictions are also utilized as supporting evidence for the assessment of bioaccumulation potential of chemicals along with read across. Currently, the effective use of read across and QSARs is examined for other hazards, including biodegradability. This paper describes the results of external validation and improvement of CATALOGIC 301C model based on more than 1000 tested new chemical substances of the publication schedule under CSCL. CATALOGIC 301C model meets all REACH requirements to be used for biodegradability assessment. The model formalism built on scientific understanding for the microbial degradation of chemicals has a well-defined and transparent applicability domain. The model predictions are adequate for the evaluation of the ready degradability of chemicals.

Metabolic activation of chemicals: in-silico simulation.

The role of metabolism in prioritising chemicals according to their potential adverse health effects is extremely important given the fact that innocuous parents can be transformed into toxic metabolites. Our recent efforts in simulating metabolic activation of chemicals are reviewed in this work. The application of metabolic simulators to predict biodegradation (microbial degradation pathways), bioaccumulation (fish liver metabolism), skin sensitisation (skin metabolism), mutagenicity (rat liver S-9 metabolism) are discussed. The ability of OASIS approach to predict metabolism (toxicokinetics) and toxicity (toxicodynamics) of chemicals resulting from their metabolic activation in a single modelling platform is an important advantage of the method. It allows prioritisation of chemicals due to predicted toxicity of their metabolites.

Tuning and predicting the wetting of nanoengineered material surface.

The wetting of a material can be tuned by changing the roughness on its surface. Recent advances in the field of nanotechnology open exciting opportunities to control macroscopic wetting behaviour. Yet, the benchmark theories used to describe the wettability of macroscopically rough surfaces fail to fully describe the wetting behaviour of systems with topographical features at the nanoscale. To shed light on the events occurring at the nanoscale we have utilised model gradient substrata where surface nanotopography was tailored in a controlled and robust manner. The intrinsic wettability of the coatings was varied from hydrophilic to hydrophobic. The measured water contact angle could not be described by the classical theories. We developed an empirical model that effectively captures the experimental data, and further enables us to predict the wetting of surfaces with nanoscale roughness by considering the physical and chemical properties of the material. The fundamental insights presented here are important for the rational design of advanced materials having tailored surface nanotopography with predictable wettability.

Antibacterial properties of nitric oxide-releasing porous silicon nanoparticles.

In this study, the antibacterial efficacy of NO-releasing porous silicon nanoparticles (pSiNPs) is reported. NO-releasing pSiNPs were produced via the conjugation of S-nitrosothiol (SNO) and S-nitrosoglutathione (GSNO) donors to the nanoparticle surfaces. The release of the conjugated NO caused by the decomposition of the conjugated SNO and GSNO was boosted in the presence of ascorbic acid. The released NO was bactericidal to Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), and eliminated bacterial growth within 2 h of incubation without compromising the viability of mammalian cells. These results demonstrate the advantages of NO-releasing pSiNPs for antibacterial applications, for example, in chronic wound treatment.

Controlled and sustained release of pharmaceuticals via single step solvent-free encapsulation.

Herein, we report a novel and solvent-free technique for the encapsulation of pharmaceuticals that allows achieving controllable release rates. This method utilizes the deposition of a plasma polymer coating of controlled chemistry and thickness on the outer surface of drug particles placed under continuous agitation.

Effect of Surface Chemical Functionalities on Collagen Deposition by Primary Human Dermal Fibroblasts.

Surface modification has been identified as an important technique that could improve the response of the body to implanted medical devices. Collagen production by fibroblasts is known to play a vital role in wound healing and device fibrous encapsulation. However, how surface chemistry affects collagen I and III deposition by these cells has not been systematically studied. Here, we report how surface chemistry influences the deposition of collagen I and III by primary human dermal fibroblasts. Amine (NH3), carboxyl acid (COOH), and hydrocarbon (CH3) surfaces were generated by plasma deposition. This is a practically relevant tool to deposit a functional coating on any type of substrate material. We show that fibroblasts adhere better and proliferate faster on amine-rich surfaces. In addition, the initial collagen I and III production is greater on this type of coating. These data indicates that surface modification can be a promising route for modulating the rate and level of fibrous encapsulation and may be useful in informing the design of implantable biomedical devices to produce more predictable clinical outcomes.

Plasma polymerised polyoxazoline thin films for biomedical applications.

Poly(2-oxazoline)s are emerging revolutionary biomaterials, exhibiting comparable and even superior properties to well-established counterparts. Overcoming current tedious wet synthesis methods, we report solvent-free and substrate independent, plasma polymerised nanoscale biocompatible polyoxazoline coatings capable of controlling protein and cell adhesion, and significantly reducing biofilm build up.

[Treatment of short esophageal stricture in children]. / Lechenie korotkikh striktur pishchevoda u detei.

The authors find it necessary to identify a nosological entity of short esophageal strictures, up to 1.5-2.0 cm long, from the specific features of their formation, clinical manifestations and from the possibility of widely using transesophageal methods of treatment. Among them, a procedure for intraesophageal compression of the scarring ring by using two types of devices in 64 patients was analysed. There was a positive result in 86% of the patients. The remaining children underwent surgical interventions: resection of an esophageal portion with esophagus-esophagus anastomosis and colesophagoplasty. No deaths were recorded. To objectivize the indications for either method of treatment, the authors recommend esophageal NMR tomography.

Laparoscopic vs open resection for rectal carcinoma--a prospective analysis.

UNLABELLED: In the recent years, laparoscopic surgery has established itself worldwide as a method of treatment for colorectal cancer. Several prospective randomized trials comparing laparoscopic with open resection of the colon, showing the advantages of laparoscopic surgery in terms of a shorter hospital stay, faster recovery of intestinal transit and physical activity in equivalent survival and recurrence rate. However, in many of the studies the data on laparoscopic resection for rectal cancer are scarce and it is still controversial. AIM: In this report, we aimed to make a comparative analysis of the clinical and oncological outcomes after laparoscopic and open rectal resection in patients with a rectal cancer. MATERIAL AND METHODS: We compare and analyze prospectively data from two groups of patients with rectal cancer--66 undergoing laparoscopic and 47 undergoing open rectal resection respectively. Both groups were selected with comparable demographic characteristics (gender, age, body mass index), ASA class (American Society of Anesthesiologists), tumor stage, type of neoadjuvant radiochemotherapy and operations. The data were statistically processed. RESULTS: The mean age was 61, body mass index ranged from 18 to 42. The frequency of conversion was 6.06%. Postoperative complications were similar in both groups, except for wound infection was lower for the laparoscopic group (p = 0.02). The laparoscopic group had a shorter hospital stay (7 and 5 days respectively p < 0.01), faster recovery of intestinal motility (3 and 4.5 days respectively, p < 0.001) compared with the open group. Three-year survival rate and the rate of local and late recurrences were identical in both groups. CONCLUSIONS: Laparoscopic surgery is applicable in the treatment of rectal cancer with similar oncologic outcomes compared with conventional surgery and has all the advantages of miniinvasive methods. There is a need for further randomized studies to refine the applicability of laparoscopic rectal resection for cancer.

Surgical treatment of benign diseases of the gastroesophageal junction in clinic of endoscopic surgery at MMA during the period 2005-2012: pathophysiology, surgical techniques and trends of their use.

UNLABELLED: Treatment of the diseases of the gastroesophageal junction is one of the serious problems faced by gastroenteorologist and surgeons. In contrast to the proton pump inhibitors (PPI) surgery achieves a long symptoms free period. Laparoscopic surgery has its advantages as an alternative to conventional surgery. The purpose of this study was to compare the obtained results from patients treated with laparoscopic surgical methods to the results of the patients treated with conventional surgery and conservative treatment with PPI. MATERIALS AND METHODS: The present study includes 99 patients: 90 patients with diaphragmatic hernia and gastroesophageal reflux disease (GERD), 8 patients with achalasia and a benign stricture of the lower third of the esophagus. All patients were operated by laparoscopic techniques. 72% of the 99 patients were women and 28% men. The average age of patients was 62 years. RESULTS: The majority of our patients had mixed hiatal hernia--55.5%, followed by axial (23.3%) and hiatal (13.3%). The most common method we used was anterior fundoplication (85.5%), we used the Nissen fundoplication in 7.8% of the patients, crurorhaphy with mesh in 4.4% and plain crurorhaphy in 2.2%. All patients had a mild postoperative period. Analgesia with prophenid is done only in the first 24 hr. The average hospital stay of the patients was 3 days. CONCLUSIONS: Partial laparoscopic fundoplication is a method of choice for the anti-reflux surgery compared to conventional surgery and drug therapy. Dysphagia is rare in patients with anterior fundoplication and is easily influenced by conservative treatment, that's why is our preferred method.

Simulation of chemical metabolism for fate and hazard assessment. III. New developments of the bioconcentration factor base-line model.

The new development of the bioconcentration factor (BCF) base-line model of Dimitrov et al. [SAR QSAR Environ. Res. 6 (2005), pp. 531-554] is presented. The model applicability domain was expanded by enlarging the training set of the model up to 705 chemicals. The list of chemical-dependent mitigating factors was expanded by including water solubility of chemicals. The original empirical term for estimating ionization of chemicals was mechanistically analysed using two different approaches. In the first one, the ionization potential of chemicals was estimated based on the acid dissociation constant (pK(a) ). This term was found to be less adequate for inclusion in the ultimate BCF model, due to overestimating ionization of chemicals. The second approach, estimating the ionization as a ratio between distribution and partition coefficients (log P and log D), was found to be more successful. The new ionization term allows modelling of chemicals with both acidic and basic functionalities and chemicals undergoing different degrees of ionization. The significance of the different mitigating factors which can reduce the maximum bioconcentration potential of the chemicals was re-formulated and model parameters re-evaluated.

Surface-plasmon-mediated single-molecule fluorescence through a thin metallic film.

We demonstrate that fluorescence of single molecules in the nanometric vicinity of a thin gold film can be effectively excited and detected through the film with an epi-illumination scanning confocal microscope. A full theoretical treatment of the fluorescence signal indicates that both excitation and emission are surface-plasmon mediated. Remarkably, the number of photons detectable from chromophores perpendicular to the interface is enhanced by the presence of the metal.