Singularities, Lax degeneracies and Maslov indices of the periodic Toda chain

The n-particle periodic Toda chain is a well known example of an integrable but nonseparable Hamiltonian system in R^{2n}. We show that Sigma_k, the k-fold singularities of the Toda chain, ie points where there exist k independent linear relations amongst the gradients of the integrals of motion, coincide with points where there are k (doubly) degenerate eigenvalues of representatives L and Lbar of the two inequivalent classes of Lax matrices (corresponding to degenerate periodic or antiperiodic solutions of the associated second-order difference equation). The singularities are shown to be nondegenerate, so that Sigma_k is a codimension-2k symplectic submanifold. Sigma_k is shown to be of elliptic type, and the frequencies of transverse oscillations under Hamiltonians which fix Sigma_k are computed in terms of spectral data of the Lax matrices. If mu(C) is the (even) Maslov index of a closed curve C in the regular component of R^{2n}, then (-1)^{\mu(C)/2} is given by the product of the holonomies (equal to +/- 1) of the even- (or odd-) indexed eigenvector bundles of L and Lmat.Comment: 25 pages; published versio

Отношение жителей мегаполиса к репродуктивному донорству (на примере Екатеринбурга)

Аbstract. The paper presents the findings of a population survey conducted in the city of Ekaterinburg in 2019 (1300 respondents). The study aimed at measuring the citizens' awareness about reproductive donation and their attitudes to different types of reproductive donation in general and in connection with the specificity of reproductive material. The data were analyzed in the context of Goffman's concept of social stigma and the results of similar works by other authors. The majority of the respondents are aware of reproductive donation and have a positive attitude towards it. The level of awareness, as well as the prevalence of positive attitudes, depends on the specificity of the reproductive material. The most wellknown and accepted technology is sperm donation, while the most controversial is embryonic donation. More than half of the respondents (52%) consider the embryo a human being, and 47% have a negative attitude towards embryo donation. Perceptions of embryo status are correlated with gender, family history, and religious beliefs. Most of the respondents say that they themselves are not ready to become donors of genetic material, and the main motive of those who become a reproductive donor is financial interest. The study reveals a clear gap between the general attitudes towards donation, when it is perceived in abstract, and situations of personal relatedness to the field of reproductive donation. In the latter case, the attitude towards reproductive donation becomes much more positive. The results of the study strongly suggest that the involvement of third parties in the parenting process is ethically and psychologically ambiguous, and it requires further study together with the position of the involved parties. Since Ekaterinburg, on the one hand, demonstrates trends inherent in capital cities, and on the other, has a clear regional specificity, this data may reflect the current attitude of the population of all large Russian cities towards reproductive donation. © 2021 Russian Public Opinion Research Center, VCIOM. All rights reserved

Global Dimension of Polynomial Rings in Partially Commuting Variables

For any free partially commutative monoid $M(E,I)$, we compute the global dimension of the category of $M(E,I)$-objects in an Abelian category with exact coproducts. As a corollary, we generalize Hilbert's Syzygy Theorem to polynomial rings in partially commuting variables.Comment: 11 pages, 2 figure

Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function

Background Human S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins that are associated with many diseases including cancer, chronic inflammation and neurological disorders. S100A12 is an important factor in host/parasite defenses and in the inflammatory response. Like several other S100 proteins, it binds zinc and copper in addition to calcium. Mechanisms of zinc regulation have been proposed for a number of S100 proteins e.g. S100B, S100A2, S100A7, S100A8/9. The interaction of S100 proteins with their targets is strongly dependent on cellular microenvironment. Results The aim of the study was to explore the factors that influence S100A12 oligomerization and target interaction. A comprehensive series of biochemical and biophysical experiments indicated that changes in the concentration of calcium and zinc led to changes in the oligomeric state of S100A12. Surface plasmon resonance confirmed that the presence of both calcium and zinc is essential for the interaction of S100A12 with one of its extracellular targets, RAGE – the Receptor for Advanced Glycation End products. By using a single-molecule approach we have shown that the presence of zinc in tissue culture medium favors both the oligomerization of exogenous S100A12 protein and its interaction with targets on the cell surface. Conclusion We have shown that oligomerization and target recognition by S100A12 is regulated by both zinc and calcium. Our present work highlighted the potential role of calcium-binding S100 proteins in zinc metabolism and, in particular, the role of S100A12 in the cross talk between zinc and calcium in cell signaling

Clinical significance of collchicine in pharmacotherapy of cardiovascular pathology in patients with hyperuricemia in rheumatic diseases

For a long time, there has been scientific debate about the appropriateness of prescribing drugs to lower the level of uric acid in patients without clinical manifestations of gout. Long-term hyperuricemia is known to be the cause of gout and gouty arthritis. However, an increased level of uric acid is often found in a number of other diseases (metabolic syndrome, kidney disease, cardiovascular disease, psoriasis). Clinical evidence suggests that uric acid-lowering therapy slows the progression of cardiovascular disease and chronic kidney disease. And, if in rheumatological practice this issue still remains a subject of discussion, then the cardiological community by 2019 has clearly defined the indications for starting urate-lowering therapy. The Consensus on the Management of Patients with Hyperuricemia and High Cardiovascular Risk strongly recommends that the practitioner prescribe drugs to control hyperuricemia in hypertensive patients. The need to control the level of uric acid is reflected in the relevant sections of the Clinical Guidelines for the Management of Patients with Arterial Hypertension, 2020. This article provides a review of the literature on the etiology, pathophysiology, pharmacotherapy of hyperuricemia in patients with cardiovascular and rheumatic diseases. A separate section is devoted to scientific studies of the effects of colchicine in advanced therapy for CVD and RD. A clinical case of observation of a patient with newly diagnosed psoriatic arthritis, hyperuricemia, high cardiovascular risk is presented. The peculiarity of this clinical case is the onset of the disease after orthopedic surgery on the knee joints, high comorbidity and poor tolerance of standard basic therapy. The use of colchicine stabilized the patient’s condition. Thus, in clinical practice, it is necessary to take into account the role of hyperuricemia in the pathogenesis of inflammation in cardiovascular pathology. Colchicine may be the drug of choice for patients with hyperuricemia at high cardiovascular risk

Risk factors for osteoporosis in patients with rheumatoid arthritis

Aim of the study was to investigate risk factors for osteoporosis (OP) in patients with rheumatoid arthritis (RA). Material and methods. We observed 110 patients with a verified diagnosis of RA. RA was diagnosed based on the 2010 EULAR/ACR clinical classification. All patients with RA were divided into 2 groups: with ОP (53 patients) and without ОP signs (57 patients). Bone mineral density (BMD) was assessed by dual-energy X-ray densitometry (DEXA), the diagnosis was made on the basis of WHO recommendations. All patients underwent a standard clinical and laboratory examination, in addition the following parameters were studied: 25-OH vitamin D, C-terminal telopeptide of type I collagen (CTX-1), N-terminal propeptide of procollagen I (P1NP) content in the blood, the ratio of calcium to urine creatinine. Results. We found a statistically significant relationship between the presence of ОP and the following clinical signs: patient weight (р = 0.014), duration of RA course (р = 0.024), and the presence of erosive changes (р = 0.014). In addition, a relationship was found between the presence of OP and lower BMD in the Ward area (Ward) and the greater trochanter area (Troch) (р < 0.0001). It was also shown that taking glucocorticosteroid drugs for more than 3 months significantly increases the risk of developing ОP (р < 0.0001). Conclusions. Identification of risk groups for patients at risk for the development of OP is of great practical importance. The factors given in the article can be adjusted towards normalization in order to reduce the degree of possible risk, which is quite feasible in practice

Фотодинамическая терапия экпериментальной саркомы М-1 крыс с фотосенсибилизатором борированным хлорином

On model of experimental sarcoma М-1 the efficiency of photodynamic therapy (PDT) has been studied with using as photosensitizer boronated chlorine. The doses of the last was 5 mg/kg of mass of an animal. A laser irradiation was spent at densities of energy 150 J/cm2 and power 0,25 V/cm2. Effect PDT was estimated by percent of animals with full regress of the tumor, to quantity of relapses, and in situation of the tumor growth by dynamic of coefficient of absolute it increase. Experiences have been lead on 6 pubertal rats. As the control not treated animals with tumor served. Researches have shown, that efficiency of PDT depends on a dose boronated chlorine and conditions of a laser irradiation. Представлены результаты изучения динамики накопления в опухоли и здоровых тканях и фотодинамической активности борированного хлорина у беспородных крыс с саркомой М-1. Показано, что индекс контрастности опухоль/здоровые ткани достигает своего максимального значения через 3,5 ч после внутрибрюшинного введения борированного хлорина в дозе 5 мг/кг. При про- ведении облучения (плотность энергии 150 Дж/см2, плотность мощности 0,25 Вт/см2) через 3,5 ч после введения фотосенсибилизатора в дозах 1,25; 2,5 и 5 мг/кг к 48-му дню наблюдения у всех животных зарегистрирована полная регрессия опухоли, что свидетельствует о высокой фотодинамической активности борированного хлорина.

Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients

Background: Various human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study was designed to determine the role of myocardial and plasmatic miR-21 in the maladaptive remodeling of the extracellular matrix induced by pressure overload in aortic stenosis (AS) patients and the clinical value of miR-21 as a biomarker for pathological myocardial fibrosis. Methods: In left ventricular biopsies from 75 AS patients and 32 surgical controls, we quantified the myocardial transcript levels of miR-21, miR-21-targets and ECM- and TGF-β-signaling-related elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS patients. In situ hybridization of miR-21 wasperformed in myocardial sections. Results: The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with controls and correlated directly with the echocardiographic mean transvalvular gradients. miR-21 overexpression was confined to interstitial cells and absent in cardiomyocytes. Using bootstrap validated multiple linear regression, the variance in myocardial collagen expression was predicted by myocardial miR-21 (70% of collagen variance) or plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK and PDCD4, and effectors of TGF-β signaling. Conclusions: Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis

LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association

<p>Abstract</p> <p>Background</p> <p>In patients with severe aortic stenosis (AS), long-term data tracking surgically induced effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiovascular MRI (CMR) offers the ability to serially track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability.</p> <p>Hypothesis</p> <p>We hypothesize that changes in LV structure and function following aortic valve replacement (AVR) are detectable by CMR and once triggered by AVR, continue for an extended period.</p> <p>Methods</p> <p>Tweny-four patients of which ten (67 ± 12 years, 6 female) with severe, but compensated AS underwent CMR pre-AVR, 6 months, 1 year and up to 4 years post-AVR. 3D LV mass index, volumetrics, LV geometry, and EF were measured.</p> <p>Results</p> <p>All patients survived AVR and underwent CMR 4 serial CMR's. LVMI markedly decreased by 6 months (157 ± 42 to 134 ± 32 g/m^<b>2</b>, p < 0.005) and continued trending downwards through 4 years (127 ± 32 g/m^<b>2</b>). Similarly, EF increased pre to post-AVR (55 ± 22 to 65 ± 11%,(p < 0.05)) and continued trending upwards, remaining stable through years 1-4 (66 ± 11 vs. 65 ± 9%). LVEDVI, initially high pre-AVR, decreased post-AVR (83 ± 30 to 68 ± 11 ml/m2, p < 0.05) trending even lower by year 4 (66 ± 10 ml/m^<b>2</b>). LV stroke volume increased rapidly from pre to post-AVR (40 ± 11 to 44 ± 7 ml, p < 0.05) continuing to increase non-significantly through 4 years (49 ± 14 ml) with these LV metrics paralleling improvements in NYHA. However, LVmass/volume, a 3D measure of LV geometry, remained unchanged over 4 years.</p> <p>Conclusion</p> <p>After initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. Via CMR, surgically induced benefits to LV structure and function are durable and, unexpectedly express continued, albeit markedly incomplete improvement through 4 years post-AVR concordant with sustained improved clinical status. This supports down-regulation of both mRNA and MMP activity acutely with robust suppression long term.</p