Analysis of Transferrin in the Urine of Patients with Bladder Cancer Using Nanobodies.

It is known that the saturation ratio of transferrin (Tf) with iron in human blood is an important clinical parameter. Specific antibodies can be used to analyze subtle changes in the relative abundance of different forms of transferrin potentially associated with a pathological process. Recently, the authors of this study were able to obtain and characterize highly specific single-domain antibodies (nanobodies) that predominantly recognize the iron-saturated (holo-Tf) or iron-unsaturated (apo-Tf) form of transferrin. In this work, under conditions closer to physiological than in the previous experiments, we further demonstrated that these unique nanobodies have extremely high differential binding specificity for different forms of Tf in different human biological fluids. Using these nanobodies, we were able to analyze for the first time relative abundance of the transferrin forms in urine samples from the patients with bladder cancer (BC). We have shown that increase in the concentration of total Tf in the urine samples normalized for creatinine is associated with the degree of progress and growth of malignancy of BC. In the samples of healthy donors and in the early stages of BC (G1), Tf is detected in much smaller amounts (compared to the later stages) and only with additional concentration of the studied samples. For most of the studied urine samples from the BC patients, it is expected (as previously shown in the case of Tf in the blood of terminal ovarian cancer patients) that the concentration of apo-Tf is clearly higher than holo-Tf, especially in the case of the most advanced muscle-invasive BC. It was a surprise for us that approximately equal amounts of apo-Tf and holo-Tf were found in the urine samples of some patients with BC. We hypothesized that the holo-Tf fraction in this case could be largely represented by the "secondary complexes" formed by apo-Tf in combination with ions other than Fe3+, which accumulate in the urine of some cancer patients and are able to bind to apo-Tf, changing its conformation towards holo-Tf. By using inductively coupled plasma mass spectroscopy (ICP-MS), we obtained first results confirming our hypothesis. Preparation of the holo-Tf in these urine samples was found to be highly enriched in zinc and nickel. Also, relative enrichment in cadmium has been observed in this preparation, but at much lower concentrations. The obtained data indicate that the used nanobody, while recognizing predominantly the iron-saturated form of transferrin (holo-Tf), is also capable of binding transferrin in association with other metal ions that are different from iron. This ability could potentially open up new possibilities for investigation of relative abundance of various metal ions in association with transferrin in human biological fluids in normal and pathological conditions.

Nonlinear Propagation and Filamentation on 100 Meter Air Path of Femtosecond Beam Partitioned by Wire Mesh.

High-intensity (∼1 TW/cm2 and higher) region formed in the propagation of ∼60 GW, 90 fs Ti:Sapphire laser pulse on a ∼100 m path in air spans for several tens of meters and includes a plasma filament and a postfilament light channel. The intensity in this extended region is high enough to generate an infrared supercontinuum wing and to initiate laser-induced discharge in the gap between the electrodes. In the experiment and simulations, we delay the high-intensity region along the propagation direction by inserting metal-wire meshes with square cells at the laser system output. We identify the presence of a high-intensity region from the clean-spatial-mode distributions, appearance of the infrared supercontinuum wing, and occurrence of the laser-induced discharge. In the case of free propagation (without any meshes), the onset of the high-intensity zone is at 40-52 m from the laser system output with ∼30 m extension. Insertion of the mesh with 3 mm cells delays the beginning of the high-intensity region to 49-68 m with the same ∼30 m extension. A decrease in the cell size to 1 mm leads to both delay and shrinking of the high-intensity zone to 71-73 m and 6 m, respectively. Three-dimensional simulations in space confirm the mesh-induced delay of the high-intensity zone as the cell size decreases.

LIFE QUALITY OF EMPLOYEES OF THE NORTH-EASTERN FEDERAL UNIVERSITY (YAKUTSK).

OBJECTIVE: The aim of the study evaluate the quality of life of employees of the North Eastern Federal University. PATIENTS AND METHODS: Materials and methods: The respondents to the WHO QoL 100 questionnaire were 37 teachers and 32 support staff with an average age of 44 years. RESULTS: Results and conclusions: There is a higher correlation between assessments of overall satisfaction with the quality of life and individual areas in the group of surveyed teachers compared to the group of support staff. Comparison of the parameters of the QOL areas of teachers of NEFU with the data of similar surveys of universities in Central Russia revealed a higher assessment of such areas as the "environment", the "physical" sphere among the Yakutia's. These results indicate the adaptability of NEFU employees to environmental conditions. Also, among the respondents of the Yakutia's, there was revealed a great significance for the QOL of such a subsphere as support for relatives, friends and colleagues.

Genotype/allelic combinations as potential predictors of myocardial infarction.

In order to find new informative predictors of myocardial infarction, we performed an analysis of genotype frequencies of polymorphic markers of SELE (rs2076059, 3832T > C), SELP (rs6131, S290 N), SELL (rs1131498, F206L), ICAM1 (rs5498, K469E), VCAM1 (rs3917010, c.928 + 420A > C), PECAM1 (rs668, V125L), VEGFA (rs35569394, -2549(18)I/D), CCL2 (rs1024611, -2518A > G), NOS3 (rs1799983, E298D), and DDAH1 (rs669173, c.303 + 30998A > G) genes in the group of Russian men with myocardial infarction (N = 315) and the control group of corresponding ethnicity, gender, and age (N = 286). Using Markov chain Monte-Carlo method (APSampler), we found genotype combinations associated with increased and decreased risk of myocardial infarction. The most significant associations were detected for PECAM1*V/V + DDAH1*C (OR = 4.17 CI 1.56-11.15 Pperm = 0.005) SELE*C + VEGFA*I + CCL2*G + VCAM1*A + NOS3*D (OR = 2.74 CI 1.66-4.52 Pperm = 2.09 × 10(-5)), and VEGFA*D/D + CCL2*A + DDAH1*C (OR = 0.44 CI 0.28-0.7 Pperm = 7.89 × 10(-5)) genotype combinations.

Polymorphisms of inflammatory markers and risk of essential hypertension in Tatars from Russia.

Essential hypertension (EH) is a common disease with a clear genetic component. Inflammation and endothelial dysfunction play a prominent role in the development of persistent blood pressure elevation. The aim of the current study was to detect an association between EH and polymorphic markers in genes encoding for molecules involved in the control of intercellular interactions during the inflammation process. We analysed SNPs in SELE, SELP, SELL, ICAM1, VEGFA, IL1B, IL6, IL10 and IL12B genes in a group of 534 men of Tatar ethnicity (217 patients with EH and 317 controls). Using a Markov chain Monte-Carlo-based approach (APSampler), we found genotype and allelic combinations associated with EH. The most significant associations were observed for SELE rs2076059*C-SELP rs6131*A-VEGFA -2549*I-IL1B rs16944*C (p = 3.42 × 10(-5), FDR q = 0.035) and SELE rs2076059*C-SELP rs6131*A-IL12B rs3212227*C-IL1B rs16944*C (p = 323 × 10(-4), FDR q = 0.035).

Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly.

BACKGROUND: Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome. AIMS: To identify a causative gene for SOPH syndrome. METHODS: Genomewide homozygosity mapping was conducted in 33 patients in 30 families. RESULTS: The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome. CONCLUSION: These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.

Rhaponticum uniflorum and Serratula centauroides Extracts Attenuate Emotional Injury in Acute and Chronic Emotional Stress.

In modern life, the use of plant stress-protectors has taken on particular significance due to the wide distribution of neurosis-like and neurotic diseases caused by neuroendocrine-immune system imbalance. Special attention has been paid to the plants containing ecdysteroids, i.e., hormone-like bioactive substances with high adaptogenic activity. The article deals with the study of bioactivity of two plant extracts as Rhaponticum uniflorum (L.) DC. and Serratula centauroides L. with a high content of ecdysteroids and phenolic compounds. The models of acute and chronic emotional stress in white rats were used to estimate the stress-protective activity of R. uniflorum and S. centauroides extracts. Both extracts showed the stress-protective effect via inhibiting the development of signs induced by single and long-term effects of stress factors. In acute stress, the development of Selye's triad signs was less pronounced against the background of the plant remedies introduction. In chronic stress, the extracts prevented the development of anxiety-depressive syndrome. Besides, R. uniflorum and S. centauroides extracts banned the development of stress-induced injuries in the brain cortex and had a neuroprotective effect on ischemia against chronic stress. The stress-protective effects of both plant extracts were based on a decrease of hyperactivation of the central stress-promoting systems (sympathoadrenal, hypothalamic-pituitary-adrenal) due to their GABA-mimetic effects. Peripheral mechanisms were connected with the inhibition of free radical oxidation processes and with an increase in the endogenous antioxidant system activity. Thus, R. uniflorum and S. centauroides extracts have a high potential to increase non-specific body resistance against acute and chronic emotional stress effects.

Case Report: Coil Occlusion of Two Congenital Coronary Cameral Fistulas Connecting Right and Left Circumflex Arteries to the Right Ventricle: An Innovative Stent-Assisted Technique.

BACKGROUND: Coronary cameral fistulas (CCFs) are rare congenital malformations consisting of abnormal vascular connections between coronary arteries and cardiac chambers, often incidentally found during cardiac catheterizations. CASE SUMMARY: A 66-year-old female asymptomatic patient, without cardiovascular risk factors and a history of varicose veins lower extremities and coronavirus disease 2019 (COVID-19) pneumonia in December 2020, was diagnosed by coronary angiography with two large coronary cameral fistulas connecting the distal right coronary artery (RCA) and the distal left circumflex artery (LCx) to the right ventricle (RV). Additional imaging modalities such as two-dimensional transthoracic/transesophageal echocardiography and three-dimensional multidetector CT angiography were required to confirm the fistula's pathway (location, number, and size), which was difficult to delineate using selective coronary angiography alone. After heart team discussion, with the aim to reduce the risk of embolization, an innovative stent-assisted coil occlusion antegrade technique was used with optimal immediate results. DISCUSSION: Even though our otherwise asymptomatic patient was not the best suitable candidate for an interventional procedure (large vessels, multiple fistulas without distal narrowing, distal portion of the fistula not accessible with the closure device), the innovative stent-assisted fistula coil occlusion technique to stabilize the first coil and deploy safely the additional ones resulted to be key for successful and complete obliteration of the abnormal congenital vascular connections.

Chlorin e6-cholesterol conjugate and its copper complex. Simple synthesis and entrapping in phospholipid vesicles.

Synthesis of 13'[(cholest-5-en)-3beta-yloxyethoxycarbamoyl]-chlorin e6 starting from methylpheophorbide and 3beta(2-hydroxy)-ethoxycholest-5-ene is presented, as well as the preparation of related copper complex. Both conjugates obtained may be simply incorporated in phosphatidyl choline vesicles.

Artificial intelligence: Neural network model as the multidisciplinary team member in clinical decision support to avoid medical mistakes.

OBJECTIVE: The continuous uninterrupted feedback system is the essential part of any well-organized system. We propose aLYNX concept that is a possibility to use an artificial intelligence algorithm or a neural network model in decision-making system so as to avoid possible mistakes and to remind the doctors to review tactics once more in selected cases. METHOD: aLYNX system includes: registry with significant factors, decisions and results; machine learning process based on this registry data; the use of the machine learning results as the adviser. We show a possibility to build a computer adviser with a neural network model for making a choice between coronary aortic bypass surgery (CABG) and percutaneous coronary intervention (PCI) in order to achieve a higher 5-year survival rate in patients with angina based on the experience of 5107 patients. RESULTS: The neural network was trained by 4679 patients who achieved 5-year survival. Among them, 2390 patients underwent PCI and 2289 CABG. After training, the correlation coefficient (r) of the network was 0.74 for training, 0.67 for validation, 0.71 for test and 0.73 for total. Simulation of the neural network function has been performed after training in the two groups of patients with known 5-year outcome. The disagreement rate was significantly higher in the dead patient group than that in the survivor group between neural network model and heart team [16.8% (787/4679) vs. 20.3% (87/428), P = 0.065)]. CONCLUSION: The study shows the possibility to build a computer adviser with a neural network model for making a choice between CABG and PCI in order to achieve a higher 5-year survival rate in patients with angina.

Synthesis and Anti-Platelet Activity of Thiosulfonate Derivatives Containing a Quinone Moiety.

Thiosulfonate derivatives based on quinones were synthesized for studying "structure-activity relationship" compounds with an acylated and a free amino-group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed.

Ursodeoxycholic acid dose-dependently improves liver injury in rats fed a methionine- and choline-deficient diet.

AIM: The data on the beneficial effect of ursodeoxycholic acid (UDCA) in non-alcoholic steatohepatitis (NASH) are controversial. The difference of opinion is connected with UDCA dosage to be used. Therefore, we evaluated the dose-dependent efficacy of UDCA in experimental NASH. METHODS: Male Wistar rats were fed the methionine- and choline-deficient (MCD) diet for 10 weeks. Rats were administrated UDCA (10, 20, 40 and 80 mg/kg bodyweight intragastrically) after 6 weeks of the MCD diet. RESULTS: Animals fed the MCD diet developed severe steatohepatitis. Treatment with UDCA dose-dependently decreased liver damage, but only high-dose UDCA (80 mg/kg) significantly diminished ultrastructural changes in addition to preventing steatosis, ballooning and inflammatory changes in the liver. The activities of serum marker enzymes and the content of liver triglyceride and blood glucose were increased in MCD diet-fed rats, but decreased in all the UDCA-treated groups. Serum insulin concentration was decreased whereas the quantitative insulin sensitivity check index did not changed in MCD diet-fed groups. Serum tumor necrosis factor-α content was strongly increased after MCD diet and normalized in the UDCA-treated rats, with the most pronounced effect in the highest dose groups, 40 and 80 mg/kg. The contents of endogenous ethanol in blood and intestinal mucus were increased in MCD diet-fed rats which were significantly lowered by UDCA (40 and 80 mg/kg per day). CONCLUSION: The present data demonstrate a beneficial effect of UDCA that manifested by the decrease of liver steatosis, inflammatory signs and serum tumor necrosis factor-α content especially of the highest 40 and 80 mg/kg day doses.