Vascular targeted optical theranostics: enhanced photoplethysmography imaging of laser-induced singlet oxygen effects.

The work considers a theranostic system that implements a multimodal approach allowing the simultaneous generation of singlet oxygen and visualization of the various parameters of the vascular bed. The system, together with the developed data processing algorithm, has the ability to assess architectural changes in the vascular network and its blood supply, as well as to identify periodic signal changes associated with mechanisms of blood flow oscillation of various natures. The use of this system seems promising in studying the effect of laser-induced singlet oxygen on the state of the vascular bed, as well as within the framework of the theranostic concept of treatment and diagnosis of oncological diseases and non-oncological vascular anomalies.

Polarized phonons carry angular momentum in ultrafast demagnetization.

Magnetic phenomena are ubiquitous in nature and indispensable for modern science and technology, but it is notoriously difficult to change the magnetic order of a material in a rapid way. However, if a thin nickel film is subjected to ultrashort laser pulses, it loses its magnetic order almost completely within femtosecond timescales1. This phenomenon is widespread2-7 and offers opportunities for rapid information processing8-11 or ultrafast spintronics at frequencies approaching those of light8,9,12. Consequently, the physics of ultrafast demagnetization is central to modern materials research1-7,13-28, but a crucial question has remained elusive: if a material loses its magnetization within mere femtoseconds, where is the missing angular momentum in such a short time? Here we use ultrafast electron diffraction to reveal in nickel an almost instantaneous, long-lasting, non-equilibrium population of anisotropic high-frequency phonons that appear within 150-750 fs. The anisotropy plane is perpendicular to the direction of the initial magnetization and the atomic oscillation amplitude is 2 pm. We explain these observations by means of circularly polarized phonons that quickly absorb the angular momentum of the spin system before macroscopic sample rotation. The time that is needed for demagnetization is related to the time it takes to accelerate the atoms. These results provide an atomistic picture of the Einstein-de Haas effect and signify the general importance of polarized phonons for non-equilibrium dynamics and phase transitions.

Evolution of anti-modified protein antibody responses can be driven by consecutive exposure to different post-translational modifications.

BACKGROUND: Besides anti-citrullinated protein antibodies (ACPA), rheumatoid arthritis patients (RA) often display autoantibody reactivities against other post-translationally modified (PTM) proteins, more specifically carbamylated and acetylated proteins. Immunizing mice with one particular PTM results in an anti-modified protein antibody (AMPA) response recognizing different PTM-antigens. Furthermore, human AMPA, isolated based on their reactivity to one PTM, cross-react with other PTMs. However, it is unclear whether the AMPA-reactivity profile is "fixed" in time or whether consecutive exposure to different PTMs can shape the evolving AMPA response towards a particular PTM. METHODS: Longitudinally collected serum samples of 8 human individuals at risk of RA and 5 with early RA were tested with ELISA, and titers were analyzed to investigate the evolution of the AMPA responses over time. Mice (13 per immunization group in total) were immunized with acetylated (or carbamylated) protein (ovalbumin) twice or cross-immunized with an acetylated and then a carbamylated protein (or vice versa) and their serum was analyzed for AMPA responses. RESULTS: Human data illustrated dynamic changes in AMPA-reactivity profiles in both individuals at risk of RA and in early RA patients. Mice immunized with either solely acetylated or carbamylated ovalbumin (AcOVA or CaOVA) developed reactivity against both acetylated and carbamylated antigens. Irrespective of the PTM-antigen used for the first immunization, a booster immunization with an antigen bearing the other PTM resulted in increased titers to the second/booster PTM. Furthermore, cross-immunization skewed the overall AMPA-response profile towards a relatively higher reactivity against the "booster" PTM. CONCLUSIONS: The relationship between different reactivities within the AMPA response is dynamic. The initial exposure to a PTM-antigen induces cross-reactive responses that can be boosted by an antigen bearing this or other PTMs, indicating the formation of cross-reactive immunological memory. Upon subsequent exposure to an antigen bearing another type of PTM, the overall reactivity pattern can be skewed towards better recognition of the later encountered PTM. These data might explain temporal differences in the AMPA-response profile and point to the possibility that the PTM responsible for the initiation of the AMPA response may differ from the PTM predominantly recognized later in time.

Expression and Content of Protein LC3B in Gastric Cancer Tissue, Relationship with Expression of mTOR, AMPK in Gastric Cancer Tissue and HER2 and PD-L1 Status of the Tumor.

Analysis of HER2 status of the tumor and expression of mTOR, AMPK showed a decrease in mTOR mRNA level in HER2+ tumors in comparison with HER- status. The appearance of PD-L1+ transformed cells in the tumor was associated with increased expression of the LC3B gene and elevated content of the corresponding protein measured after treatment.

AKT/mTOR Signal Cascade and Expression of PD-1, PD-L1, and PD-L2 in Gastric Cancer.

The peculiarities of gastric cancer development associated with the expression levels of components of the AKT/mTOR signaling cascade and PD, PD-L1, PD-L2 have not yet been identified. We revealed the fundamental changes in the expression AKT/mTOR and PD receptors and their ligands associated with dissemination of gastric cancer. An increase in the mRNA level of all components of this cascade was demonstrated. The expression of mTOR and AKT decreased against the background of enhanced expression of PTEN phosphatase. The increase in the expression of PD-1 receptors and PD-L1 and PD-L2 ligands was most pronounced in patients with distant metastases.

Effect of the chemical structure of an equatorial ligand on the spin crossover properties of the Fe(III) complex with 4-styrylpyridine axial ligands.

In order to study the effect of the chemical structure of the equatorial ligand on the spin state of the Fe(iii) ion in complexes with invariable photoisomerizable 4-styrylpyridine axial ligands and different tetradentate Schiff bases, several new Fe(iii) complexes have been first synthesized, characterized, and studied by UV-vis, NMR, and EPR spectroscopies. The general chemical formula of the complexes is [Fe(SB)Sp2]BPh4·MeOH, where Sp is trans-4-styrylpyridine and SB are dianions of Schiff bases: salen, bzacen, and acen [salen = N,N'-ethylenebis(salicylaldimine) 1, acen = N,N'-ethylenebis(acetylacetonylideneimine) 2, and H2bzacen = N,N'-ethylenebis(benzoylacetonylideneimine) 3]. The results of the EPR and NMR measurements of the complexes both in the solid state and in solutions showed that the more methyl groups and less aromatic rings in the equatorial ligand, the more abrupt spin-crossover was observed in the complex. The dependence of the magnetic properties of the complexes on the state of matter and the presence of a solvent (powder, liquid solutions, and vitrified solutions) are noted.

Phase stabilization of an attosecond beamline combining two IR colors.

We present a phase-stabilized attosecond pump-probe beamline involving two separate infrared wavelengths for high-harmonic generation (HHG) and pump or probe. The output of a Ti:sapphire laser is partly used to generate attosecond pulses via HHG and partly to pump an optical parametric amplifier (OPA) that converts the primary Ti:sapphire radiation to a longer wavelength. The attosecond pulse and down-converted infrared are recombined after a more than 20-m-long Mach-Zehnder interferometer that spans across two laboratories and separate optical tables. We demonstrate a technique for active stabilization of the relative phase of the pump and probe to within 450 as rms, without the need for an auxiliary continuous wave (cw) laser. The long-term stability of our system is demonstrated with an attosecond photoelectron streaking experiment. While the technique has been shown for one specific OPA output wavelength (1560 nm), it should also be applicable to other OPA output wavelengths. Our setup design permits tuning of the OPA wavelength independently from the attosecond pulse generation. This approach yields new possibilities for studying the wavelength-dependence of field-driven attosecond electron dynamics in various systems.

Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.

BACKGROUND: Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists ≤40 (YOs). METHODS: A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were carried out to identify factors associated with burnout. RESULTS: Total of 737 surveys (all ages) were collected from 41 European countries. Countries were divided into six regions. Results from 595 (81%) YOs were included (81% medical oncologists; 52% trainees, 62% women). Seventy-one percent of YOs showed evidence of burnout (burnout subdomains: depersonalization 50%; emotional exhaustion 45; low accomplishment 35%). Twenty-two percent requested support for burnout during training and 74% reported no hospital access to support services. Burnout rates were significantly different across Europe (P < 0.0001). Burnout was highest in central European (84%) and lowest in Northern Europe (52%). Depersonalization scores were higher in men compared with women (60% versus 45% P = 0.0001) and low accomplishment was highest in the 26-30 age group (P < 0.01). In multivariable linear regression analyses, European region, work/life balance, access to support services, living alone and inadequate vacation time remained independent burnout factors (P < 0.05). CONCLUSIONS: This is the largest burnout survey in European Young Oncologists. Burnout is common amongst YOs and rates vary across Europe. Achieving a good work/life balance, access to support services and adequate vacation time may reduce burnout levels. Raising awareness, support and interventional research are needed.

Gouy phase shift for annular beam profiles in attosecond experiments.

Attosecond pump-probe measurements are typically performed by combining attosecond pulses with more intense femtosecond, phase-locked infrared (IR) pulses because of the low average photon flux of attosecond light sources based on high-harmonic generation (HHG). Furthermore, the strong absorption of materials at the extreme ultraviolet (XUV) wavelengths of the attosecond pulses typically prevents the use of transmissive optics. As a result, pump and probe beams are typically recombined geometrically with a center-hole mirror that reflects the larger IR beam and transmits the smaller XUV, which leads to an annular beam profile of the IR. This modification of the IR beam can affect the pump-probe measurements because the propagation that follows the reflection on the center-hole mirror can strongly deviate from that of an ideal Gaussian beam. Here we present a detailed experimental study of the Gouy phase of an annular IR beam across the focus using a two-foci attosecond beamline and the RABBITT (reconstruction of attosecond beating by interference of two-photon transitions) technique. Our measurements show a Gouy phase shift of the truncated beam as large as 2π and a corresponding rate of 50 as/mm time delay change across the focus in a RABBITT measurement. These results are essential for attosecond pump-probe experiments that compare measurements of spatially separated targets.

[Improving renal cancer care].

The article reviews the rates of incidence, late diagnosis and mortality from kidney cancer in Primorsky Krai. The authors address the issues of improving primary and specialized medical care by introducing a three-level health care system and restructuring of hospital beds. They propose a new medical technology for assessing the individual risk of kidney cancer and present a program of measures and organizational modules for prevention, early diagnosis and reduction of mortality from kidney cancer.

Attosecond dynamical Franz-Keldysh effect in polycrystalline diamond.

Short, intense laser pulses can be used to access the transition regime between classical and quantum optical responses in dielectrics. In this regime, the relative roles of inter- and intraband light-driven electronic transitions remain uncertain. We applied attosecond transient absorption spectroscopy to investigate the interaction between polycrystalline diamond and a few-femtosecond infrared pulse with intensity below the critical intensity of optical breakdown. Ab initio time-dependent density functional theory calculations, in tandem with a two-band parabolic model, accounted for the experimental results in the framework of the dynamical Franz-Keldysh effect and identified infrared induction of intraband currents as the main physical mechanism responsible for the observations.

[Current approaches to diagnosing and treating eosinophilic granulomatosis with polyangiitis: The 2015 international guidelines].

The 2015 international guidelines for the diagnosis and treatment of eosinophilic granulomatosis with polyangiitis, formerly known as the Churg-Strauss syndrome, are detailed and an attempt is made to expand an evidence base, by attracting more recent available publications. The new guidelines should not be regarded as final standards; these are primarily to extend the possibilities of choosing a personified management strategy for patients with eosinophilic granulomatosis with polyangiitis and to serve as the starting point for further in-depth investigations.

Ah-receptor-independent stimulation of hepatoma 27 culture cell proliferation by polycyclic aromatic hydrocarbons.

The proliferative effect of some compounds that are aryl hydrocarbon (Ah) receptor ligands was studied on hepatoma 27 cells with absent expression of Ah receptor. Compounds of the polycyclic aromatic hydrocarbon (PAH) class benzo/a/pyrene, 3-methylcholanthrene, 7,12-dimethylbenz/a/anthracene, and benzo/e/pyrene as well as ß-naphthoflavone (ß-NF) and chlorinated hydrocarbon Aroclor 1254 were studied. It was found that carcinogenic PAH and ß-NF stimulate cell proliferation both under conditions of standard serum content and in a medium with low serum content. More efficient stimulation of proliferation was observed in the case of low serum content. Aroclor 1254 and benzo/e/pyrene did not stimulate cell proliferation. Stimulation of proliferation was accompanied by activation of the ERK1/2-dependent MAP-kinase cascade. Benzo/a/pyrene caused a decrease in the number of cells in G1 phase of the cell cycle and increase in number of cells in G2/M phases under conditions of cell growth in media with low serum content. Carcinogenic PAH and ß-NF activated transcription factor AP-1, and in this case activation was more pronounced in cells grown in medium with low serum content. A possible mechanism of activation of proliferation by an Ah receptor-independent pathway is discussed.

Vital staining of nerve structures with fluorescent dyes and optical determination of acetylcholine in the somatic muscle of the earthworm Lumbricus terrestris.

Experiments with fluorescent dyes showed that high concentrations of K(+) ions in the medium depolarize the membrane and enhance exo-endocytosis in nerve structures, which is accompanied by an increase in acetylcholine concentration in the somatic muscle of earthworm. In the presence of BAPTA and without Ca(2+) exo-endocytosis is sharply decelerated, the level of acetylcholine in the muscle decreases, but remains relatively high.

[Immunocytochemical identification of synaptotagmin 1, syntaxin 1, N-type Ca(2+)-channel and nicotinic cholinoreceptor in motor neuromuscular junctions of earthworm somatic muscle Lumbricus terrestris].

The somatic muscle of earthworm contains myoneural synapses forming clusters of "synaptic buttons". In these "buttons", the proteins syntaxin 1, synaptotagmin 1 and alpha 1B subunit of the Ca(2+)-channel of N-type were identified. We suppose that "synaptic buttons" contain a limited number of active zones due to their small size (1-2 microm) and the pattern of distribution of proteins of exo-endocytotic cycle. The postsynaptic membrane of cholinetgic synapses contains nicotinic acetylcholine receptors capable to bind alpha-bungarotoxin. The area of location of receptors on postsynaptic membrane is strictly limited to the region of synaptic contact.

[Activation of transcription factor NF-kappaB by carcinogenic polycyclic aromatic hydricarbons].

Effect of carcinogenic polycyclic aromatic hydrocarbons (PAH) benzo(a)pyrene (BP) and 3-methylcholanthrene (MC) on transcription factor NF-kappaB activation was studied. The determination of NF-kappaB activity was performed by two different methods: determination of mRNA expression of NF-kappaB-dependent I-kappaB gene, and determination of transcription activity of co-transfected with the plasmid containing the luciferase reporter gene under the NF-kappaB-sensitive promoter. As a subject of inquiry the hepatoma cell cultures HepG2 expressed Ah receptor and G27 not expressed Ah receptor were used. BP and MC weekly enhanced NF-kappaB activity in proliferating HepG2 cells. The enhance of NF-kappaB activity was significantly higher in resting cells. NF-kappaB activation by BP and MC in hepatoma G27 cells was significantly higher in hepatima G27 cells than in HepG2 cells both in proliferating and resting cells. The role of Ah receptor in PAH action on NF-kappaB activation is discussed.

[Investigation vesicle cycle in nerve formations in somatic muscle of the earthworm Lumbricus terrestris].

Luminous spots with a diameter of 1-2 microm, which are clusters of "synaptic buds", were revealed in the muscular wall of the earthworm using endocytotic fluorescent dyes FM1-43, FM2-10 and FM4-64. Application of the membrane probe Dil that is capable of being subjected to anterograde axonal transport to abdominal ganglia of the nervous chain, and subsequent (in a day) staining of nerve formations by endocytotic dye FM4-64 showed complete imposition of the emission data of the dyes that fluoresce in different parts of the spectrum. Using fluorescent marker DiBAC4(3) showed an increased emission of neural elements with increasing concentration of K+ in the extracellular environment. Application of FM2-10 showed that the higher concentration of K+ in solution, and hence the depolarization of the nerve cells, the faster the upload of the dye, and vice versa, the process slowed down in the absence of K+ in the medium. The seizure and removal of FM2-10 were blocked in calcium-free solutions in the presence of Ca2+ buffers, BABTA or BABTA-AM, but only after a preliminary 40 min incubation. The processes of exo- and endocytosis occurred in the clusters of synaptic "buds" and were preserved in conditions of "rest". This vesicle cycle depends on membrane potential and concentration of K+ and Ca2+, and, it is very likely that the calcium sensor operates on the principle "all or nothing".

[Phosphorus and calcium metabolism and the cardiovascular system status in patients with early-stage chronic renal disease].

AIM: To define the impact of phosphorus and calcium metabolic disturbances in patients with early-stage chronic renal disease (CRD) on the cardiovascular system. SUBJECTS AND METHODS: The levels of phosphate (P), calcium, parathyroid hormone (PTH), 25(OH) vitamin D and 1,25(OH)2 vitamin D, serum lipidogram, carotid artery intima-media thickness (IMT), and X-ray degree of abdominal artery calcification (AAC) were determined and echocardiography, electrocardiography and blood pressure monitoring were made in 465 patients with Stages I-V CRD who did not receive renal replacement therapy (of them, 73.5% of the patients had early (I to III) stages). RESULTS: Blood 1,25(OH)2D was related inversely to left ventricular (LV) posterior wall thickness, blood pressure (BP), triglycerides, and the degree of AAC and correlated directly to the severity of LV diastolic dysfunction and inversely to IMT, the presence of coronary heart disease and heart failure (HF). ACC, LV hypertrophy, and arterial hypertension (AH) were more significant in patients with higher serum levels PTH and P. CONCLUSION: In patients with early-stage CRD, phosphorus and calcium metabolic disturbances promote the development of AH, vascular and cardiac valvular calcification, myocardial hypertrophy, and HF.

Development of a duplex real-time TaqMan PCR assay with an internal control for the detection of Mycoplasma gallisepticum and Mycoplasma synoviae in clinical samples from commercial and backyard poultry.

In this study, we report the development and validation of a duplex real-time polymerase chain reaction (PCR) assay with an internal control using TaqMan-labelled probes for the detection of Mycoplasma gallisepticum and Mycoplasma synoviae (duplex MGMS PCR). The MGMS PCR was highly specific with a sensitivity of 7 and 1 colony-forming units/ml for M. gallisepticum and M. synoviae, respectively, using dilution of pure culture that corresponds to 34 and 29 DNA copies per reaction. Validation of the assay was completed with 260 and 27 pooled samples (tracheal swabs) from commercial chickens and turkeys, respectively, with potential M. gallisepticum and M. synoviae involvement and 42 samples (palatine cleft swabs) from backyard geese and ducks. Using isolation as the gold standard, the MGMS PCR was more sensitive than isolation and the analytical sensitivity was 0.944 and 0.958 for M. gallisepticum and M. synoviae, respectively. In comparison with a gapA-based assay (gapA PCR) and a 16S rRNA-based assay (16S PCR) for M. gallisepticum and M. synoviae, respectively, the results agreed for 94.5% and 96.6%, respectively. The use of the internal control allowed monitoring of proper extraction and inhibition of amplification that was detected in 12 samples. The duplex MGMS PCR was shown to be superior to the presently reported real-time PCR assays in terms of combination of sensitivity, specificity and capacity of detection of more than one target in a single tube. In conclusion, the duplex MGMS PCR was highly specific, sensitive, and reproducible and could be used on clinical samples from commercial chickens, turkeys and backyard poultry including ducks and geese.