Predictive role of quantification of myocardial fibrosis using delayed contrast-enhanced magnetic resonance imaging in nonischemic dilated cardiomyopathies: a systematic review and meta-analysis

Aim. The present study aims to provide a systematic review and meta-analysis to investigate the prognostic role of assessing the severity of myocardial fibrosis using delayed contrast-enhanced magnetic resonance imaging in nonischemic dilated cardiomyopathies.Material and methods. We searched PubMed, Google Scholar for studies that examined the predictive value of quantifying late gadolinium enhancement (LGE) areas in patients with nonischemic dilated cardiomyopathy. Unadjusted hazard ratios (HR) from studies with similar scoring criteria were pooled for meta-analysis.Results. Nine studies were retrieved from 782 publications for this systematic review and meta-analysis. In total, 2389 patients (mean age, 51,9 years; mean follow-up, 39,3 months) were included in the analysis. Meta-analysis showed the extent of LGE was associated with an increased risk of arrhythmic end point (HR: 1,09/1% LGE; 95% CI: 1,02-1,18; p=0,01), major adverse cardiovascular events (HR: 1,07/1% LGE; 95% CI: 1,01-1,13; p=0,03) and all-cause mortality (HR: 1,09/1% LGE; 95% CI: 1,04-1,13; p<0,0001).Conclusion. The severity of LGE by cardiac magnetic resonance predicts arrhythmic events (ventricular arrhythmia and sudden death), major adverse cardiovascular events and all-cause mortality. Assessment of LGE can be used as an effective tool for stratifying risk in patients with nonischemic dilated cardiomyopathy

Kinetics of fragmentation and dissociation of two-strand protein filaments: Coarse-grained simulations and experiments.

While a significant body of investigations have been focused on the process of protein self-assembly, much less is understood about the reverse process of a filament breaking due to thermal motion into smaller fragments, or depolymerization of subunits from the filament ends. Indirect evidence for actin and amyloid filament fragmentation has been reported, although the phenomenon has never been directly observed either experimentally or in simulations. Here we report the direct observation of filament depolymerization and breakup in a minimal, calibrated model of coarse-grained molecular simulation. We quantify the orders of magnitude by which the depolymerization rate from the filament ends koff is larger than fragmentation rate k- and establish the law koff/k- = exp[(ε‖ - ε⊥)/kBT] = exp[0.5ε/kBT], which accounts for the topology and energy of bonds holding the filament together. This mechanism and the order-of-magnitude predictions are well supported by direct experimental measurements of depolymerization of insulin amyloid filaments.This research was supported by the ERC, EPSRC, BBSRC, and the Newman Foundation.This is the author accepted manuscript. The final version is available from the American Institute of Physics via http://dx.doi.org/10.1063/1.496236

Spinning and rotating strings for N=1 SYM theory and brane constructions

We obtain spinning and rotating closed string solutions in AdS_5 \times T^{1,1} background, and show how these solutions can be mapped onto rotating closed strings embedded in configurations of intersecting branes in type IIA string theory. Then, we discuss spinning closed string solutions in the UV limit of the Klebanov-Tseytlin background, and also properties of classical solutions in the related intersecting brane constructions in the UV limit. We comment on extensions of this analysis to the deformed conifold background, and in the corresponding intersecting brane construction, as well as its relation to the deep IR limit of the Klebanov-Strassler solution. We briefly discuss on the relation between type IIA brane constructions and their related M-theory descriptions, and how solitonic solutions are related in both descriptions.Comment: 35 pages. Dedicated to the memory of Ian I. Kogan. References adde

Folded Three-Spin String Solutions in AdS_5 x S^5

We construct a spinning closed string solution in AdS_5 x S^5 which is folded in the radial direction and has two equal spins in AdS_5 and a spin in S^5. The energy expression of the three-spin solution specified by the folding and winding numbers for the small S^5 spin shows a logarithmic behavior and a one-third power behavior of the large total AdS_5 spin, in the long string and in the short string located near the boundary of AdS_5 respectively. It exhibits the non-regular expansion in the 't Hooft coupling constant, while it takes the regular one when the S^5 spin becomes large.Comment: 14 pages, LaTeX, no figures, a reference adde

ASSESSMENT OF THE SENSITIVITY OF NEW CRITERIA FOR SYSTEMIC SCLEROSIS IN RUSSIAN PATIENT POPULATION

Systemic sclerosis (SS) is a progressive connective tissue disease, the prognosis of which largely depends on the time of adequate therapy initiation. Low sensitivity of the 1980 American College of Rheumatology (ACR) SS classification criteria for identifying patients with early stage of the disease, and with its limited form in particular, has necessitated revision of existing SS diagnostic standards and elaboration of more sensitive criteria that allow to establish the diagnosis when the first sign of the disease appear.Objective: to compare the sensitivity of the novel SS criteria of ACR and European League against Rheumatism (ACR/EULAR) 2013 and the 1980 ACR criteria in different stages of the disease.Subjects and methods. The investigation enrolled 302 patients who had been diagnosed by experts as having SS and followed up at the V.A. Nasonova Research Institute of Rheumatology in 2007–2013. The patients’ mean age was 49±13 years (18 to 80 years); male to female ratio – 1:9 (31 and 271), that of patients with diffuse and limited SS – 1:2 (105 and 197); mean duration of the disease from the first non-Raynaud’s syndrome was 8.2±7.0 years (6 months to 36 years). Physical examination, nailfold capillaroscopy, chest radiography or computed tomography, echocardiography for the determination of pulmonary artery systolic pressure and SS-specific antibodies evaluation were performed.Results. 273 (90%) patients fulfilled the novel ACR/EULAR 2013 SS criteria. 76 (25%) patients had skin thickening above the metacarpophalangeal (MPC) joints in both hands; 263 (87%) – finger skin thickening [70 (23%) – finger swelling, 192 (64%) – thickening of all fingers distal to the MPC joints], 141 (47%) – digital ischemia [79 (26%) – digital pitting scars, 20 (7%) – digital ulcers, 42 (14%) – digital pitting scars and ulcers], 134 (44%) – telangiectasias, 276 (91%) – capillaroscopic changes, 225 (78%) – pulmonary hypertension (PH) or interstitial lung disease (ILD) [15 (5%) – PH 185 (61%) – ILD, 35 (12%) – ILD and PH], 301 (99%) – Raynaud’s phenomenon, and 185 (61%) – SS autoantibodies [138 (46%) – anti-Scl-70 antibodies (a-Scl-70), 42 (14%) – anti-centromere antibodies (ACA), 5 (1.7%) – ACA and a-Scl-70]. 216 (72%) patients fulfilled 1980 ACR SS criteria, and all of them met the novel criteria. With the latter, SS could be additionally diagnosed in 57 more (18%) patients.Conclusion. The 2013 ACR/EULAR SS classification criteria have much higher sensitivity than the 1980 ACR criteria. The sensitivity of the novel criteria remained at the level of 90% in all, including the earliest, stages of the disease while the ACR criteria allowed to confirm diagnosis of SS in only half of patients with a disease duration of less than 1 year

IgG4-RELATED DISEASE. CLINICAL NOTES

IgG4-related diseases are a new nosological entity that encompasses a few previously known diseases. IgG4-related systemic disease is diagnosed if two or more affected organs are detected. This group of diseases has two similar signs: serological (elevated serum IgG4 subclass concentrations) and histological (organ and tissue infiltration from plasmo-cytes secreting IgG4, and eosinophils, and the development of fibrosclerosis and phlebitis obliterans). The paper describes two cases. In one case, a multisystemic disease was observed virtually at its onset whereas in the other this lesion was diagnosed several years after the natural course of the disease

Спектрометрия ионной подвижности N-метилимидазола и возможности его определения

Objectives. To determine the ion mobility of N-methylimidazole, establish the structure of ions corresponding to characteristic signals, and determine the detection limit of N-methylimidazole on the ion-drift detector Kerber.Methods. Ion mobility spectrometry was used to study the ionization processes. The enthalpies of the reactions of monomer and dimer ions were calculated in the ORCA 4.1.1 software by the B3LYP density functional method with a set of basic functions 6-31G (d, p).Results. The drift time and ion mobility values of N-methylimidazole were determined. A method for mathematical processing of spectra and a program for its implementation was developed. The changing peculiarities of the ion mobility spectrum during measurement at a given time were studied. According to the interpretation of the spectrum signals, the structure of the generated ions was proposed, and the enthalpies of ion formation were determined.Conclusions. The characteristic signal of the N-methylimidazole ion protonated at the nitrogen atom of the pyridine type was revealed. It was found that two signals in the ion mobility spectra of N-methylimidazole correspond to the presence of the monomer and dimer ions. The detection limit of N-methylimidazole on the ion-drift detector Kerber was determined, amounting to 3 pg.Цели. Определение значений ионной подвижности N-метилимидазола. Установление строения ионов, соответствующих характерным сигналам. Определение предела обнаружения N-метилимидазола на ионно-дрейфовом детекторе Кербер.Методы. Метод спектрометрии ионной подвижности был использован для исследования процессов ионизации. Энтальпии реакций мономерных и димерных ионов расчитаны в программе ORCA 4.1.1 методом функционала плотности B3LYP с набором базисных функций 6-31G(d,p).Результаты. Определены значения времени дрейфа и ионной подвижности N-метилимидазола. Разработана методика математической обработки спектров и программа для ее реализации. Изучены особенности изменения характера спектра ионной подвижности в процессе измерения в данный момент времени. Предложено строение генерируемых ионов в соответствии с интерпретацией сигналов спектра. Определены энтальпии образования ионов.Выводы. Выявлен характеристический сигнал иона N-метилимидазола, протонированного по атому азота пиридинового типа. Установлено, что два сигнала в спектрах ионной подвижности N-метилимидазола соответствуют наличию мономерной и димерной формы ионов. Определен предел обнаружения N-метилимидазола на ионно-дрейфовом детекторе Кербер, составляющий 3 пг

Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study.

Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure

Interrelations between viral load and cellular immunity in patients with COVID-19 of varying severity

Assessment of viral load levels in various biological samples taken from the respiratory tract can be an indicator of an ongoing process of active viral replication and may be used to monitor severe respiratory viral infections. The study of the relationship between SARS-CoV-2 viral load and immunological laboratory parameters is an important step in the search for clinical markers of COVID-19.The aim of this research was to quantify viral load in patients with COVID-19 and to identify the relation-ship between viral load and changes in the parameters of the cellular component of the immune system.A laboratory examination was carried out on 74 patients diagnosed with COVID-19, they were divided into 3 groups based on the severity of the disease: mild, moderate, severe. Total viral load in clinical samples was determined by the number of SARS-CoV-2 RNA copies per 100 copies of the reference RNaseP gene.     A comprehensive assessment of the cellular component of the immune system was performed using flow cytometry and direct monoclonal antibodies, and the IL-6, and C-reactive protein concentrations were determined.We revealed a relationship between the development of serious clinical conditions in the patients with COVID-19, and the levels of viral load. High levels of viral RNA in biological samples correlate with main indicators of the T cell component of the immune system associated with disease severity. In a subgroup of patients with an extremely high viral load, strong positive correlations were found between the relative numbers of cytotoxic lymphocytes (CD3+CD8+), activated T lymphocytes (CD3+HLA-DR+), as well as absolute and relative numbers of activated B lymphocytes and NK cells (CD3-CD25+).Laboratory monitoring of the cellular component of the immune system, along with the assessment of viral loads, should improve  early assessment of clinical condition in the patients with COVID-19. Changes   in expression levels of activation markers on immune cells can be potentially viewed as indicators of recovery during COVID-19