Determinants of prognosis and management of patients with pulmonary hypertension due to left heart disease: a systematic review

Patients with pulmonary hypertension (PH) associated with left heart disease usually have a complex comorbidity status and a postcapillary component of PH. The presence and identification of a combined post-/precapillary PH in a cohort of patients with left heart disease is reflected in the more pronounced structural and functional right ventricular changes due to higher pulmonary vascular resistance. Patients with combined post-/ precapillary PH have reduced exercise tolerance and PH phenotype similar to pulmonary arterial hypertension. Detection of combined PH is critical as it may influence the prognosis and management of patients. This review presents modern prognosis markers for patients with PH due to left heart disease, which can be used in clinical practice. The results of randomized clinical trials and pilot studies on the expansion of treatment options in group 2 patients, including the use of PAH-specific agents, were analyzed. The prospects for the treatment of this cohort of patients are discussed

ИННОВАЦИИ В ФИНАНСОВОЙ АНАЛИТИКЕ

In this paper as the main feature of innovation in the financial health of a company analyst view the shift to two circuits of key interests of owners of capital (financial stakeholders). Justifi ed by differences key financial systems within the contour ownership interest and the lender three projections: liquidity, the current economic efficiency and growth. In the paper as the main feature of the innovation in the analysis of the financial health of a company is considered a transition to the two circuits of the interests of the key owners of financial capital (financial stakeholders). Justifi ed differences of key financial indicator systems in the framework of the outline of the interests of the owner and the lender by three projections: liquidity, efficiency and the quality of growth. The examples of Russian companies have different interpretations of financial targets and indicators with a choice of activities.В статье как главная особенность инноваций в аналитике финансового здоровья компании рассматривается переход к двум контурам интересов ключевых владельцев капитала (финансовых стейкхолдеров). Обоснованы различия систем ключевых финансовых показателей в рамках контура интересов собственника и кредитора по трем проекциям: ликвидности, текущей экономической эффективности и роста. Приведены примеры российских компаний, по разному трактующих стоимостные цели и выбор показателей анализа деятельности

ФИНАНСОВЫЕ ИННОВАЦИИ В СТРАТЕГИЧЕСКОМ АНАЛИЗЕ БАНКОВСКОГО БИЗНЕСА

In paper we identified the financial innovations in the strategic analysis of bank business. On the real data analytical research is executed and empirical proofs of practical applicability of the new financial performance, allowing to create the mechanism of strategic management by shareholder value in bank are received. The received results can be used for monitoring of acceptance of managerial decisions from the party and in interests of owners of bankВ работе выявлены финансовые инновации в области стратегического анализа банковского бизнеса. На реальных данных выполнено аналитическое исследование и получены эмпирические доказательства практической применимости новых финансовых показателей, позволяющих создать механизм стратегического управления акционерной стоимостью в банке. Полученные результаты могут быть использованы для мониторинга принятия управленческих решений со стороны и в интересах собственников банка

Оценка селекционного материала межвидовых гибридов Allium ascalonicum L. и Allium cepa L.

Relevance. Shallots are an independent botanical species. It easily crosses with onions, has a medium-sized bulb, keeps well, gives rich greens. Shallot and onion hybrids have a higher yield, less nesting, and a large bulb mass. Work on the creation of interspecific hybrids of shallots and onions has been under way since 2000.Methods. The aim of the research was to study the hybrids of Allium ascalonicum L. x Allium cepa L. and Allium cepa L. x Allium ascalonicum L. by a complex of characters in comparison with their maternal forms. Samples from the Urals were taken as initial forms for hybridization.Results. 268 promising hybrids were obtained, of which 33 were selected for further study. The results of the study showed the advantage of hybrid forms, where shallots were the parent form. A significant advantage of hybrids over parental forms was revealed in terms of yield, average and maximum bulb weight.Актуальность. Лук шалот – самостоятельный ботанический вид. Он легко скрещивается с луком репчатым, имеет некрупную луковицу, хорошо хранится, дает богатую зелень. Гибриды шалота и репчатого имеют более высокую урожайность, меньшую гнездность, большую массу луковицы. Работа по созданию межвидовых гибридов шалота и репчатого ведется с 2000 года.Материал и методика. Целью исследований было изучение гибридов Allium ascalonicum L. х Allium cepa L. и Allium cepa L. х Allium ascalonicum L. по комплексу признаков в сравнении с их материнскими формами. В качестве исходных форм для гибридизации были взяты сортообразцы с Урала.Результаты. Получено 268 перспективных гибридов, из которых для дальнейшего изучения отобрано 33. Результаты исследования показали преимущество гибридных форм, где в качестве материнской формы был лук шалот. Существенное преимущество гибридов перед родительскими формами выявлено по признакам: урожайность, масса средней и максимальной луковицы

Фенотип пациентов с легочной гипертензией вследствие патологии левых отделов сердца: особенности патофизиологии и дифференциальной диагностики

The cohort of patients with postcapillary pulmonary hypertension (PH), associated with the left heart diseases, is the most numerous, but is still not fully understood. This review presents the pathophysiological aspects of the PH group 2 development as well as the influence of comorbid pathology on the course of the PH. The features of the differential diagnosis of post-capillary PH and combined post-/ precapillary PH, as well as methods of the differential diagnosis of these forms of PH with pulmonary arterial hypertension using modern non-invasive and invasive approaches are discussed.Наиболее многочисленной, при этом не до конца изученной остается когорта пациентов с посткапиллярной легочной гипертензией (ЛГ), ассоциированной с заболеваниями левых отделов сердца. В данном обзоре детально представлены патофизиологические аспекты развития ЛГ на фоне патологии левых отделов сердца на примере сердечной недостаточности с низкой/сохранной фракцией выброса, а также описано влияние коморбидной патологии на характер течения ЛГ. Обсуждены особенности дифференциального диагноза посткапиллярной и комбинированной (пост- и прекапиллярной) форм ЛГ, а также подходы к дифференциальному диагнозу данных форм ЛГ с легочной артериальной гипертензией с использованием современных неинвазивных и инвазивных подходов.

SCLERODERMA SYSTEMATICA WITH INTERSTITIAL LUNG LESION: COMPARATIVE CLINICAL CHARACTERISTICSWITH PATIENTS WITHOUT LUNG LESION

Objective. To compare disease history data and clinical and laboratory parameters in patients with scleroderma systematica (SDS) with high-resolution computed tomography (HRCT)-verified interstitial lung lesion (ILL) versus those without lung involvement. Subjects and methods. An examination was made in 138 patients with SDS who had been consecutively admitted in 2006-2008, female/male ratio, 124 : 14; limited : diffuse : mixed forms, 78 : 40 : 20; mean age, 47±13 years; median disease duration, 6 (2.5 11) years. The history data (occupational hazards, smoking, respiratory diseases) and clinical manifestations of SDS and laboratory data were studied. The diagnosis of ILL was established on the basis of chest HRCT. Results. According to HRCT data, the signs of varying ILL were found in 82% of the patients with SDS. The duration of SDS was similar in the patients with and without lung involvement; but the latter were younger at the time of disease onset. There were no significant differences between the groups compared in history data, clinical forms of SDS, the frequency of involvement of visceral organs and systems. Crepitation was heard only in the patients with ILL. The frequency of respiratory manifestations increased with a larger number of the involved lung segments. The prevalence of ILL was found to be positively correlated with age at the onset of SDS (r=0.29;

STUDY OF THE EFFICIENCY AND SAFETY OF MYCOPHENOLATE MOFETIL THERAPY IN PATIENTSWITH SYSTEMIC SCLERODERMA

Interstitial lung disease (ILD) is one of the major causes of death in systemic scleroderma (SSD). Treatment of these patients remains difficult and controversial. Mycophenolate mofetil (MPM) has been in vitro shown to inhibit overproduction of type I collagen and hence may be effective against SSD. Objective: to study the efficiency and safety of MPM therapy in patients with SSD and clinically relevant ILD in an open-label prospective study. Subjects and methods. Ten patients with SSD (7 and 3 with its diffuse and limited forms, respectively) and ILD were given MPM in combination with glucocorticoids (mean daily dose was 10+4 mg). The mean MPM therapy duration was 11.4+1.3 months. The Rodnan total skin thickness score, flexion index, forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and European Scleroderma Study Group (EScSG) activity index were estimated and a 6-minute walk test (6MWT) was carried out before and after MPM therapy. Results. After therapy, the whole group showed a significant reduction in skin scores from 12.9+9.8 to 5.6+3.2 (p=0.036) and EScSG from 3.9+1.4 to 2.25+1.03 (p=0.015) and an increase in exercise tolerance from 446+155 to 535+78 m (p=0.03) as evidenced by 6MWT. The degree of flexion contractures decreased from 15+21 to 3.7+11.3 mm (p>0.05). FVC (77.8+18.7% versus 73.8+11.3%) and DLCO (45+14.4% versus 42+16.4%) were significantly unchanged. A 10% or more clinically significant fall was noted in FVC and DLCO in 3 and 1 patients, respectively. In the remaining patients, the lung functional test results remained stable. MPM tolerability was satisfactory. All the patients completed their course of treatment. Conclusion. Stabilization of lung function with higher exercise tolerance and significantly reduced skin density allow therapy with MPM in combination with low-dose glucocorticoids to be regarded as an effective and well-tolerated treatment in patients with ILD in the presence of SS

A Novel Inhibitor of Human La Protein with Anti-HBV Activity Discovered by Structure-Based Virtual Screening and In Vitro Evaluation

Background: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. Aims: This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. Methods: A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. Results: Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50 % with P,0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system prefix for active compounds screened by the library) were selected for evaluation. HBSC-11 was found to have an obvious inhibitory effect on hLa transcription and expression

Analysis of the interaction with the hepatitis C virus mRNA reveals an alternative mode of RNA recognition by the human La protein

Human La protein is an essential factor in the biology of both coding and non-coding RNAs. In the nucleus, La binds primarily to 3′ oligoU containing RNAs, while in the cytoplasm La interacts with an array of different mRNAs lacking a 3′ UUUOH trailer. An example of the latter is the binding of La to the IRES domain IV of the hepatitis C virus (HCV) RNA, which is associated with viral translation stimulation. By systematic biophysical investigations, we have found that La binds to domain IV using an RNA recognition that is quite distinct from its mode of binding to RNAs with a 3′ UUUOH trailer: although the La motif and first RNA recognition motif (RRM1) are sufficient for high-affinity binding to 3′ oligoU, recognition of HCV domain IV requires the La motif and RRM1 to work in concert with the atypical RRM2 which has not previously been shown to have a significant role in RNA binding. This new mode of binding does not appear sequence specific, but recognizes structural features of the RNA, in particular a double-stranded stem flanked by single-stranded extensions. These findings pave the way for a better understanding of the role of La in viral translation initiation