Treatment feasibility of a digital tool for brief self-help behavioural therapy for insomnia (FastAsleep)

Cognitive behavioural therapy for insomnia is efficacious and recommended for insomnia, but availability is scarce. Cognitive behavioural therapy for insomnia self-help interventions could increase availability, especially if unguided. Optimizing cognitive behavioural therapy for insomnia methods and system user-friendliness, we developed a short, digital, self-help programme—FastAsleep—based on the behavioural components of sleep restriction and stimulus control. This study investigated its feasibility and preliminary effects. Thirty media-recruited participants with moderate to severe insomnia were assessed via telephone before using FastAsleep for 4 weeks, and were interviewed afterwards. Self-ratings with web questionnaires were conducted at screening, pre-, mid- and post-treatment, and at 3-month follow-up. Primary outcomes were feasibility (credibility, adherence, system user-friendliness and adverse effects), and secondary outcomes were changes in symptom severity (insomnia, depression and anxiety). Adherence was generally high, participants' feasibility ratings were favourable, and adverse effects matched previously reported levels for cognitive behavioural therapy for insomnia. Symptoms of insomnia decreased after the treatment period (Hedge's g = 1.79, 95% confidence interval = 1.20–2.39), as did symptoms of depression and anxiety. FastAsleep can be considered feasible and promising for alleviating insomnia symptoms among patients fit for self-care. Future controlled trials are needed to establish the efficacy of FastAsleep and its suitability in a stepped care model.     

Intraoperative retinal light damage reflected in electrophysiologic data

In a series of 30 unilaterally pseudophakic patients, electroretinograms and electrooculograms were recorded 6 months postoperatively. The unoperated on fellow eyes served as controls High intraoperative retinal light exposure (3.4–7.3 mW/cm², Zeiss OPMI 6 operating microscope) caused a substantial reduction of electrophysiologic potentials. Light protection prevented deterioration of electroretinogram and electro-oculogram potentials; reducing the bulb voltage, tilting the axis of illumination, filtering short wavelengths and the use of light shields resulted in 4-log-unit lower intensities (0.8–3.7 W/cm²).Abbreviations ACL anterior chamber lens - ECCE extracapsular cataract extraction - ICCE intracapsular cataract extraction - PCL posterior chamber lens     

Pharmacodynamic Evaluation of CCI-779, an Inhibitor of mTOR, in Cancer Patients.

CCI-779 is an ester of rapamycin and inhibitor of mammalian target of rapamycin (mTOR) currently in Phase II clinical development for the treatment of patients with cancer. CCI-779 interacts with mTOR and inhibits its kinase activity, resulting in inhibition of the mTOR-regulated translational controllers p70(s6) kinase and 4E-BP1. Ultimately, CCI-779 decreases the translation of mRNAs involved in the control of the cell cycle, resulting in cell cycle arrest. The objective of this study was to develop a method to determine the pharmacodynamic effects of CCI-779 suitable for use in clinical trials. Exposure of Raji lymphoblastoid cells to increasing concentrations of rapamycin resulted in a linear concentration-dependent inhibition of p70(s6) kinase activity, suggesting that p70(s6) kinase activity could be an appropriate marker for mTOR-interacting agents. In subsequent experiments, treatment of nude mice bearing the CCI-779 susceptible breast cancer cell line MDA-468 with a single dose of 10 mg/kg CCI-779 resulted in a >80% inhibition of p70(s6) kinase activity in peripheral blood mononuclear cells (PBMCs) 72 h after treatment. Importantly, the degree of p70(s6) kinase inhibition was identical in PBMCs and simultaneously collected tumor tissue, suggesting that the PBMCs are an adequate surrogate tissue for p70(s6) kinase activity in vivo. The intrasubject coefficient of variation of p70(s6) kinase activity measured in PBMCs collected from five healthy volunteers on days 1, 4, and 8 was 14%, indicating that p70(s6) kinase activity in PBMCs remains relatively stable over time. Finally, p70(s6) kinase activity was measured in PBMCs from nine patients with renal cell cancer treated with a single dose of 25, 75, or 250 mg of CCI-779 i.v. (three patients each). PBMCs were collected on days 2, 4, and 8 after CCI-779 treatment. In this small data set, eight of the nine patients had evidence of p70(s6) kinase activity inhibition after treatment that was independent of the administered dose. There was a significant linear association between time to disease progression and inhibition of p70(s6) kinase activity 24 h after treatment. In conclusion, these results indicate that the pharmacodynamic effects of CCI-779 can be determined using a p70(s6) kinase assay in PBMCs. This assay is currently being incorporated in Phase I and II studies with CCI-779 to determine its relationship with dose and plasma concentration of the agent and its value as a predictor of treatment efficacy.     

Evolutionary Classification of Homeodomains

Purpose and Methods: We performed multiple comparisons between available amino acid (aa) sequences of homeodomain(HOM)-containing proteins from a wide spectrum of animals to create an evolutionary classification of the proteins. Results: Based on results of statistical and special computational analyses of over 500 homeodomain aa sequences (HOMs) a novel system of concepts describing complex structural correlations between homologous proteins is proposed. This system includes such notions as differentiated isofunctionality of aa, chemotype, stereotype, local functional motifs, gradual conservativeness of aa positions, and group-specific domain patterns, as well as major categories of the evolutionary classification of HOMs (Division, Type, Branch, Class, Family, Series, Variety, Sort). Using this approach, a complete structural systematics of HOMs belonging to proteomes of eukaryotic animals is proposed. Conclusions: The proposed structural classification of HOMs is in full agreement with the bulk of experimental data revealing complex functional similarities and differences among HOMs in terms of their expression patterns in developing embryos. It turn, this classification can provide answers regarding homology among homeodomains when experimental data are conflicting.     

TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

AIM: To study polymorphisms in promotor regions of tumor necrosis factor (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), and TNF-238A/G (rs361525) in patients with age-related macular degeneration (AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients (82 women, 20 men; mean age 64.2±1.2y) with AMD and 100 healthy age- and sex-matched controls (82 women, 18 men; 60±1.4y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios (OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863CC/TNF-308GA and TNF-308GA/TNF-238GG genotypes were associated with the increased risk of AMD (OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complex analysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.     

Influence of the Carbidized Tungsten Surface on the Processes of Interaction with Helium Plasma

This paper presents the results of experimental studies of the interaction of helium plasma with a near-surface tungsten carbide layer. The experiments were implemented at the plasma-beam installation. The helium plasma loading conditions were close to those expected in the ITER divertor. The technology of the plasma irradiation was applied in a stationary type linear accelerator. The impact of the helium plasma was realized in the course of the experiment with the temperatures of ~905 °C and ~1750 °C, which were calculated by simulating heat loading on a tungsten monoblock of the ITER divertor under the plasma irradiation at the load of 10 MW/m² and 20 MW/m², respectively. The structure was investigated with scanning microscopy, transmitting electron microscopy and X-ray analysis. The data were obtained showing that the surface morphology changed due to the erosion. It was found that the carbidization extremely impacted the plasma–tungsten interaction, as the plasma–tungsten interaction with the carbide layer led to the carbon sputtering and partial diffusion towards to the depth of the sample. According to these results, WC-based tungsten carbide is less protected against fracture by helium than W and W₂C. An increase in temperature leads to much more extensive surface damage accompanied by the formation of molten and recrystallized flanges.     

UV Light Irradiation Effects in P-Doped Diamonds: Total Content Determination of Phosphorus Donors

Upon the UV light irradiation of single-crystal diamonds doped with phosphorus, several effects have been observed. The integral intensity of phosphorus lines in FTIR absorption spectra under UV radiation was increased. A saturation effect depending on the power of the laser radiation was demonstrated. Narrowing of the phosphorus lines, as well as the redistribution of the intensities in their doublets caused by the Jahn–Teller distortion of the donor ground state, was observed. It was found that these effects are associated with the decompensation of the phosphorus donors. An easy, fast, sensitive, and nondestructive, fully optical method for the determination of the total phosphorus donor’s concentration in semiconducting diamonds, as well as its compensation ratio, was proposed.     

Scattering Analysis of AlGaN/AlN/GaN Heterostructures with Fe-Doped GaN Buffer

The results of the study of the influence of Fe segregation into the unintentionally doped GaN channel layer in AlGaN/AlN/GaN heterostructures with Fe-doped GaN buffer layer on the electrical properties of two-dimensional electron gas are presented. A set of several samples was grown by metal-organic vapor-phase epitaxy and characterized by the van der Pauw method. The dependence of concentration and mobility of the two-dimensional electron gas on the channel layer thickness was analyzed theoretically by self-consistent solving of 1D Poisson and Schrödinger equations and scattering rate calculations within the momentum relaxation time approximation. It was found that both concentration and mobility decreases were responsible for the increase in the sheet resistance in the structures with a thinner channel layer, with a drop in mobility being not only due to ionized impurity scattering, but also due to a combined effect of weakening of screening, lower carrier energy and change in form-factors on scattering by interface roughness, dislocations and polar optical phonons.     

ITO Thin Films for Low-Resistance Gas Sensors

Indium tin oxide thin films were deposited by magnetron sputtering on ceramic aluminum nitride substrates and were annealed at temperatures of 500 °C and 600 °C. The structural, optical, electrically conductive and gas-sensitive properties of indium tin oxide thin films were studied. The possibility of developing sensors with low nominal resistance and relatively high sensitivity to gases was shown. The resistance of indium tin oxide thin films annealed at 500 °C in pure dry air did not exceed 350 Ohms and dropped by about 2 times when increasing the annealing temperature to 100 °C. Indium tin oxide thin films annealed at 500 °C were characterized by high sensitivity to gases. The maximum responses to 2000 ppm hydrogen, 1000 ppm ammonia and 100 ppm nitrogen dioxide for these films were 2.21 arbitrary units, 2.39 arbitrary units and 2.14 arbitrary units at operating temperatures of 400 °C, 350 °C and 350 °C, respectively. These films were characterized by short response and recovery times. The drift of indium tin oxide thin-film gas-sensitive characteristics during cyclic exposure to reducing gases did not exceed 1%. A qualitative model of the sensory effect is proposed.