New laboratory criteria of the autoimmune inflammation in pulmonary sarcoidosis and tuberculosis.

Sarcoidosis and tuberculosis have many clinical and laboratory similarities, which allowed researchers to assume the presence of common pathogenetic mechanisms in the development of both diseases. Recently, much attention has been paid to investigate the autoimmune origins in these pathologies. The aim of this study is to find out the characteristics of the autoinflammatory immune response in sarcoidosis and tuberculosis. In patients with sarcoidosis (n = 93), tuberculosis (n = 28), and in healthy donors (n = 40), the serum anti-MCV concentration was measured by ELISA, and B cell subpopulations were analyzed by flow cytometry. Based on the results obtained, the formula ([B-naïve%]\[B-memory%]) * ([B-CD38%] + [B-CD5%]) / [anti-MCV] was described. The increase in the calculated index by more than 5 units with a sensitivity of 80.00% and a specificity of 93.10% (AUC = 0.926) suggest the presence of the autoimmune component, which is more typical for sarcoidosis, rather than tuberculosis patients and may serve as a diagnostic criterion.

Imbalance in B cell and T Follicular Helper Cell Subsets in Pulmonary Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease that develops due to the Th1, Th17 and Treg lymphocytes disturbance. There is an assumption, that B cells and follicular T-helper (Tfh) cells may play an important role in this disorder, as well as in several other autoimmune diseases. The aim of this study was to determine CD19+ B cells subset distribution in the peripheral blood and to define disturbance in the circulating Tfh cells subsets in patients with sarcoidosis. The prospective comparative study was performed in 2016-2018, where peripheral blood B cell subsets and circulating Tfh cell subsets were analyzed in 37 patients with primarily diagnosed sarcoidosis and 35 healthy donors using multicolor flow cytometry. In the results of our study we found the altered distribution of peripheral B cell subsets with a predominance of "naïve" (IgD + CD27-) and activated B cell (Bm2 and Bm2') subsets and a decreased frequency of memory cell (IgD+ CD27+ and IgD- CD27+) in peripheral blood of sarcoidosis patients was demonstrated. Moreover, we found that in sarcoidosis patients there are increased levels of B cell subsets, which were previously shown to display regulatory capacities (CD24+++ CD38+++ and CD5 + CD27-). Next, a significantly higher proportion of CXCR5-expressing CD45RA - CCR7+ Th cells in patients with sarcoidosis in comparison to the healthy controls was revealed, that represents the expansion of this memory Th cell subset in the disease. This is the first study to demonstrate the association between the development of sarcoidosis and imbalance of circulating Tfh cells, especially CCR4- and CXCR3-expressing Tfh subsets. Finally, based on our data we can assume that B cells and Tfh2- and Tfh17-like cells - most effective cell type in supporting B-cell activity, particularly in antibody production - may be involved in the occurrence and development of sarcoidosis and in several other autoimmune conditions. Therefore, we can consider these results as a new evidence of the autoimmune mechanisms in the sarcoidosis development.

[Psychological Characteristics of Patients With Stress-induced Arterial Hypertension: a Violation of the Regulation of Emotions as a Central Link of Pathogenesis].

GOAL: The study of emotional and personality characteristics of patients with hypertension in the workplace (HW) and comparative assessment of the effectiveness of antihypertensive therapy in these patients. MATERIAL AND METHODS: The study included 170 patients c hypertensive disease stage II, 1-2-th degree, aged 32-52 years, including 85 patients with and 85 patients without WAH, and 82 healthy subjects matched for age and sex. To carry out simulation of the situation of emotional intensity (level of claims assessment process - UE) and a modified version of the test Rosenzweig. Patients with WAH were randomized into 2 groups: patients of group 1 received bisoprolol, 2nd group -eprosartan. If target blood pressure (BP) in 2 weeks, all patients were added indapamide retard. At baseline and after 16 weeks of treatment was carried out daily monitoring of blood pressure and the working day. RESULTS: When modeling a situation of emotional intensity in patients with WAP become, compared with patients without a healthy and WAH, revealed (1) marked increase in systolic blood pressure - 16.1, 4.1 and 3.0 mmHg, respectively (p <0,001 ), (2) the dominance of motivation "avoid failure" (UP underestimated in 34.1% of cases, unformed UP - in 21.2% of cases, healthy - 14.6% and 3.7% of cases, cootvetstvenno, p<0,001 in patients without WAH - 20% and 11.8%, respectively, p<0,05). Patients with WAP become different from normal was significantly (p<0.05) the number of the selected blshim emotionally meaningful situations (9.7 and 7.8, respectively) and emotional descriptors (11 and 7, respectively). Patients with WAH differ significantly (p<0,05) more frequent than in healthy, the use of ineffective strategies of emotion regulation in an emotionally meaningful situations: the suppression of the expression of emotions (38.3 and 20.3%, respectively), rumination and disasterization (19 and 11.8%, respectively) and more rare - high performance: sequential actualization of new meanings (25.7 and 31.7%, respectively) and the strategy of interactive subject-subject transformations (12.6 and 25.2%, respectively). After 16 weeks of treatment showed a significant (p<0,001) reduction of blood pressure in the 1st and 2nd groups. The number of patients achieving target blood pressure, at 2, 4 and 6 weeks, respectively, was as follows: 14 in the bisoprolol group and 93 (100%), in the eprosartan group - 0, 52 (100%). Both groups showed significant (p <0,001) reduction in mean daytime and nighttime blood pressure in the weekdays and weekends. In the group of bisoprolol showed a significant (p <0,01) higher average daily decrease in systolic blood pressure in the working day, compared with eprosartan group (26.2 and 19.3 mm Hg, respectively). CONCLUSION: Patients with WAP become emotionally meaningful situations frequently resorted to repression of emotions, choose the inefficient strategies of emotion regulation, they noted the expressed reaction of BP in response to the emotional burden. Antihypertensive therapy based on bisoprolol, is highly effective and has advantages over circuit-based therapy with eprosartan.

A moment-based approach for DVH-guided radiotherapy treatment plan optimization.

The dose-volume histogram (DVH) is a clinically relevant criterion to evaluate the quality of a treatment plan. It is hence desirable to incorporate DVH constraints into treatment plan optimization for intensity modulated radiation therapy. Yet, the direct inclusion of the DVH constraints into a treatment plan optimization model typically leads to great computational difficulties due to the non-convex nature of these constraints. To overcome this critical limitation, we propose a new convex-moment-based optimization approach. Our main idea is to replace the non-convex DVH constraints by a set of convex moment constraints. In turn, the proposed approach is able to generate a Pareto-optimal plan whose DVHs are close to, or if possible even outperform, the desired DVHs. In particular, our experiment on a prostate cancer patient case demonstrates the effectiveness of this approach by employing two and three moment formulations to approximate the desired DVHs.

Controlling the dose distribution with gEUD-type constraints within the convex radiotherapy optimization framework.

Radiation therapy is an important modality in treating various cancers. Various treatment planning and delivery technologies have emerged to support intensity modulated radiation therapy (IMRT), creating significant opportunities to advance this type of treatment. However, one of the fundamental questions in treatment planning and optimization, 'can we produce better treatment plans relying on the existing delivery technology?' still remains unanswered, in large part due to the underlying computational complexity of the problem, which, in turn, often stems from the optimization model being non-convex. We investigate the possibility of including the dose prescription, specified by the dose-volume histogram (DVH), within the convex optimization framework for inverse radiotherapy treatment planning. Specifically, we study the quality of approximating a given DVH with a superset of generalized equivalent uniform dose (gEUD)-based constraints, the so-called generalized moment constraints (GMCs). As a bi-product, we establish an analytic relationship between a DVH and a sequence of gEUD values. The newly proposed approach is promising as demonstrated by the computational study where the rectum DVH is considered. Unlike the precise partial-volume constraints formulation, which is commonly based on the mixed-integer model and necessitates the use of expensive computing resources to be solved to global optimality, our convex optimization approach is expected to be feasible for implementation on a conventional treatment planning station.