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Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85–1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63–0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08–1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04894877.

Human papillomavirus (HPV) is a small and non-enveloped deoxyribonucleic acid (DNA) virus that infected mucosal cells. This viral genome is composed of early and late genes. Late (L) encodes the L1 and L2 proteins. The structural protein L1 is located outside the virion. It contributes to the viral attachment mechanism; hence it becomes the target for multi-strain vaccine design. This review aims to discuss the potency of conserved L1 HPV region and the innovation of multi-strain vaccines for prevention strategies of HPV infection. Bioinformatics methods in vaccine design applied for identification of conserved sequences from databases, epitopes map, antigenicity test, prediction of similarity, and autoimmune level. The multi-strain vaccine innovation initiated in this review has more benefits compared to previous vaccines based on the level of vaccine coverage via conserved regions, potential of immune cell epitopes, antigenic properties, and possibility of autoimmune when produced. Therefore, the multi-strain HPV vaccines are predicted to be more effective than previous vaccines, including bivalent or quadrivalent. In conclusion, the strategy for expanding the prevention of HPV infection could be carried out by developing a new multi-strain-based vaccine by using conserved regions in L1 capsid from all virus strains to increase the protection.

Objectives: Erythropoietin (EPO) improved cardiac regeneration in experimental models of ischemic heart disease. A pilot trial found subcutaneously administered EPO to improve surrogate markers of left ventricular (LV) function in ischemic cardiomyopathy. This clinical study tests the feasibility and safety of the intramyocardial delivery route of a long-acting EPO-analogue (C.E.R.A.) in patients with ischemic cardiomyopathy. Methods: The ALSTER C.E.R.A. trial was a Phase II, open label, 1:1 randomized, single-center study testing intramyocardial injections of long-acting EPO analogue C.E.R.A. (C.E.R.A. NOGA: once 180 µg) using the NOGA XP system versus the subcutaneous application (C.E.R.A. SC: 30µg s.c./month for 6 months) in 59 symptomatic chronic heart failure (HF) patients with impaired LV function (ejection fraction (EF) £ 45%). Results: Follow-up up to three years with both clinical and imaging endpoints found intramyocardial delivery of C.E.R.A. to be feasible, safe and to possibly attenuate LV remodeling. Patients in the C.E.R.A. NOGA group showed stable parameter for LV end-diastolic diameter and volume (LVEDD and LVEDV), while C.E.R.A. SC patients had significant dilation of the LV (C.E.R.A. NOGA vs. SC, mean ± standard error of the mean: DLVEDD 0.02±0.1mm, p=0.8 vs. 0.3±0.09mm, p=0.0026; DLVEDV 10±15.9ml, p=0.5 vs. 34.8±11.3ml, p=0.0081; ∆EF 2.4±1.2%, p=0.045 vs. -1.6±1.1, p=0.1 respectively). NYHA class significantly improved and the hospitalization rate was numerically reduced in the C.E.R.A. NOGA group, while three-year mortality was identical. Conclusions: Intramyocardial injection of C.E.R.A. is feasible, safe and possibly attenuates LV remodeling in ischemic HF patients with LV dysfunction compared to the systemic application.

Organic light-emitting diodes (OLEDs) based on carbene-metal-amide (CMA) material are fabricated to investigate the fundamental processes that drive degradation in operational CMA OLEDs. The device lifetime of CMA OLEDs decreases rapidly with increased applied current density and implies a bimolecular degradation process. Photo- and electrical degradation studies of unipolar devices show that neither holes nor electrons are involved, and degradation is only driven by excitons. Probing of the recombination zone rationalises the degradation rate in OLEDs. We observe that the rate increases with the square of the exciton density and conclude that the degradation in CMA OLEDs is primarily driven by exciton-exciton annihilation.

To investigate the relationship between epicardial adipose tissue (EAT) volume and distribution and the parameters of global cardiac and regional left atrial (LA) sympathetic activity in patients with atrial fibrillation (AF). The data of the 45 consecutive patients scheduled for an index catheter ablation (CA) for AF were analyzed. Total and peri-atrial EAT volumes were measured by cardiac CT. Parameters of global cardiac sympathetic activity and discrete sympathetic regions around LA were assessed by 123I-mIBG SPECT/CT. The patients were followed up for AF recurrences assessment during 12 months after CA. A total of 133 (mean per patient 2.96 ± 1.07) discrete 123I-mIBG uptake areas (DUAs), corresponding to typical anatomical locations of LA ganglionated plexi (GP), were identified. Peri-atrial EAT volume was associated with the number of DUAs (regression estimate, 5.1 [95% CI, 0.3–9.9], p = 0.03). There was no statistically significant association between either total or peri-atrial EAT volumes and risks of AF recurrence. The washout rate (WR) was associated with reduced risk of AF recurrence (HR = 0.95; 95% CI 0.92–0.99; p = 0.01), while left ventricular (LV) myocardium 123I-mIBG summed defect score (SDS) was linked to increased hazards of AF recurrence (HR = 1.04; 95% CI 1.01–1.08; p = 0.03). Peri-atrial EAT volume is associated with regions of sympathetic activity corresponding to typical anatomical locations of LA GP. The WR was associated with reduced risk of AF recurrence while LV myocardial SDS was linked to increased hazards of AF recurrence.

This article provides the results of study of mineral plant nutrition systems based on the "Lignohumate" fertilizer and assessment of their impact on productivity indicators and grapes quality. 4 and 6-fold treatment sys-tems in conditions of irrigation and without irrigation were studied. Research was carried out during 2018–2020 on grape varieties Moldova and Muscat rosoviy in the condi-tions of the Republic of Crimea. A positive influence of vegetation treatments with the "Lignohumate" fertilizer on yield of variety Moldova was discovered. It increased in irri-gation conditions by 11.6% (4-fold pro-cessing) and 17.0% (6-fold processing), in conditions without irrigation the yield in-creased by 6.8 and 11.3% respectively; yield of Muscat rosoviy variety gained 13.5%. Maximum mass concentration of sugars was observed in Moldova grapes after 6-fold pro-cessing system without irrigation (192.3 g / dm3) and when irrigated (195.7g / dm3); Mus-cat rosoviy had an increase in mass concentra-tion of sugars by 3.8%; treatments helped to improve organoleptic characteristics of Mol-dova variety grapes by 9.2-22.4%; the grapes that were tested with irrigation and 6-fold foliar feeding (9.3 pts) got the highest mark; to increase chlorophyll content in Moldova variety by 14.4%, in Muscat rosoviy - 7.7%. The proportion of the effect of the drug var-ied in the range from 56.2% to 93.4%, de-pending on the experiment variation. There was a decrease in cultivating cost of Moldova variety under the 6-fold processing conditions on dry land by 10.1%, while cultivating on irrigated land the cost decreased by 14.0%. The cost of cultivating the Muscat rosoviy variety is reduced by 11.1%. The profitability of cultivation of the Moldova variety increas-es by 23.4 - 69.5% depending on the mineral nutrition system, the Muscat rosoviy variety - by 27.3%. The work was conducted in ac-cordance with the agreements reg. № CITS (Center of Information Technologies and Sys-tems): АААА-А20-120052590012-3.

Objectives This study sought to determine the impact of adjunctive renal sympathetic denervation to catheter ablation in patients with atrial fibrillation (AF) and history of hypertension. Background There are limited data regarding the impact of upstream adjunctive renal sympathetic denervation (RSDN) to pulmonary vein isolation (PVI) in patients with symptomatic atrial fibrillation (AF) and hypertension. Methods The data for this study were obtained from 2 prospective randomized pilot studies, the HFIB (Adjunctive Renal Denervation to Modify Hypertension and Sympathetic tone as Upstream Therapy in the Treatment of Atrial Fibrillation)-1 (n = 30) and HFIB (Adjunctive Renal Denervation to Modify Hypertension and Sympathetic tone as Upstream Therapy in the Treatment of Atrial Fibrillation)-2 (n = 50) studies, and we performed a meta-analysis including all published studies comparing RSDN+PVI versus PVI alone up to January 25, 2020, in patients with AF and hypertension. Results At 24 months, AF recurrence occurred in 53% and 38% in the PVI and PVI+RSDN groups (p = 0.43) in the HFIB-1 study, respectively, and 27% and 25% in the PVI and PVI+RSDN groups (p = 0.80) in the HFIB-2 study, respectively. When combined in a meta-analysis including 6 studies (n = 725), adjunctive RSDN significantly decreased the risk of AF recurrence (risk ratio [RR]: 0.68; 95% confidence interval [CI]: 0.55 to 0.83; p = 0.0002; I2 = 0%) when compared with PVI. Six renal artery complications occurred in the HFIB-1 study and none occurred in the HFIB-2 study with RSDN. However, in the meta-analysis, there were no significant differences in overall complications between both groups (RR: 1.43; 95% CI: 0.63 to 3.22; p = 0.40; I2 = 7%). When compared with baseline, RDSN significantly reduced the systolic blood pressure (–12.1 mm Hg; 95% CI: –20.9 to –3.3 mm Hg; p Conclusions The pilot HFIB-1 and HFIB-2 studies did not demonstrate a benefit with RSDN as an adjunctive upstream therapy during PVI. However, in the meta-analysis, adjunctive RSDN to PVI appears to be safe, and improves clinical outcomes in AF patients with a history of hypertension.

BackgroundTo estimate the utility of pre-procedural CT-radiomic analysis of epicardial adipose tissue (EAT), and to identify patients at risk for isolated atrial fibrillation (AF) recurrence after catheter ablation (CA).MethodsThe study population (63 patients) consisted of study group (Group 1) and comparative group (Group 2). 43 patients with isolated AF referred for CA. Before CA, all of them underwent multidetector computed tomography coronary angiography. Segmentation and subsequent radiomic analysis of EAT were performed on calcium scoring series of 3D DICOM images using by 3D-Slicer. ResultsEpicardial adipose tissue in patients with isolated AF had a distinct radiomic phenotype. Thus, 45 of 93 calculated radiomic parameters of EAT, as well as EAT volume and attenuation, were significantly different between patients with isolated AF (Group 1) and persons without any arrhythmia (Group 2). Moreover, 17 radiomic parameters were significantly different in subgroups with and without AF recurrence (Group 1a and Group 1b). Multivariate regression analysis demonstrated that among all radiomic parameters only Gray Level Non-Uniformity Normalized (GLSZM) was an independent predictor of AF recurrence (OR 0.10027, 95%CI 1.0009-1.0044, p=0.002). ROC-curve analysis data showed that GLSZM >1227.4 indicates high probability of AF recurrence during 12 months (sensitivity 89.4 %, specificity 70.8 %, AUC: 0.809; p=0.001).ConclusionThe radiomic parameter GLSZM is associated with late AF recurrence after CA in patients with isolated AF. In current study GLSZM was a stronger predictor of isolated AF recurrence in multivariate analysis comparing with other established risk factors and EAT volume and attenuation.

Purpose. This multicenter, prospective registry evaluated the comparative safety and efficacy of left atrial appendage occlusion (LAAO) using the Watchman device (WD) and the Amplatzer Cardiac Plug (ACP) in patients with nonvalvular atrial fibrillation (NVAF) in real-world clinical practice in Russia. Methods. The study included data from 200 consecutive NVAF patients (66.8±7.8years, 44.5% female, median CHA2DS2VASc 4, median HAS-BLED 3) who had undergone LAAO implantation using WD (n=108) or ACP (n=92) from September 2015 to December 2017 in 5 medical centers in Russia. The primary safety endpoint was the procedure-related major adverse events, and the primary efficacy endpoint was the composite of thromboembolic events, device thrombosis, hemorrhagic events, and unexplained death during the 12-month follow-up. Results. Successful LAAO was performed in all 92 (100%) patients with ACP and 105 (97.2%) with WD (p=0.053). At 12 months, primary safety endpoint occurred in 6.5% of patients in the ACP group with no events in the WD group (6.5% vs. 0%,p=0.008). During the 12-month follow-up, the primary efficacy endpoint has occurred in 8.3% of patients in the WD group (n=9) and 1.1% of patients in the ACP group (n=1) (p=0.016). Conclusions. In this multicenter prospective registry, LAA closure with the WD was associated with significantly higher thromboembolic events rate in NVAF patients. Patients, receiving the ACP, had more procedure-related major adverse events. However, further multicenter studies are necessary to evaluate these findings.

Oral anticoagulation reduces the ischemic stroke risk in patients with nonvalvular atrial fibrillation (NVAF) but inherently increases the bleeding risk. Percutaneous left atrial appendage occlusio...

Remote magnetic navigation (RMN) can be safely and effectively utilized in patients with difficult cardiac arrhythmias and complex anatomy. Interruption of the inferior vena cava (IVC) is a rare congenital abnormality that results in the inability to use conventional femoral access in patients that require interventional procedures. The present case demonstrates the feasibility of left atrial flutter (LA) ablation using RMN via jugular approach in a patient with interruption of IVC. This article is protected by copyright. All rights reserved

OBJECTIVEIntracerebral convection-enhanced delivery (CED) has been limited to short durations due to a reliance on externalized catheters. Preclinical studies investigating topotecan (TPT) CED for glioma have suggested that prolonged infusion improves survival. Internalized pump-catheter systems may facilitate chronic infusion. The authors describe the safety and utility of long-term TPT CED in a porcine model and correlation of drug distribution through coinfusion of gadolinium.METHODSFully internalized CED pump-catheter systems were implanted in 12 pigs. Infusion algorithms featuring variable infusion schedules, flow rates, and concentrations of a mixture of TPT and gadolinium were characterized over increasing intervals from 4 to 32 days. Therapy distribution was measured using gadolinium signal on MRI as a surrogate. A 9-point neurobehavioral scale (NBS) was used to identify side effects.RESULTSAll animals tolerated infusion without serious adverse events. The average NBS score was 8.99. The average maximum volume of distribution (Vdmax) in chronically infused animals was 11.30 mL and represented 32.73% of the ipsilateral cerebral hemispheric volume. Vdmax was achieved early during infusions and remained relatively stable despite a slight decline as the infusion reached steady state. Novel tissue TPT concentrations measured by liquid chromatography mass spectroscopy correlated with gadolinium signal intensity on MRI (p = 0.0078).CONCLUSIONSProlonged TPT-gadolinium CED via an internalized system is safe and well tolerated and can achieve a large Vdmax, as well as maintain a stable Vd for up to 32 days. Gadolinium provides an identifiable surrogate for measuring drug distribution. Extended CED is potentially a broadly applicable and safe therapeutic option in select patients.

Background Pulmonary artery denervation (PADN) procedure has not been applied to patients with residual chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA). Objectives This study sought to assess the safety and efficacy of PADN using remote magnetic navigation in patients with residual CTEPH after PEA. Methods Fifty patients with residual CTEPH despite medical therapy at least 6 months after PEA, who had mean pulmonary artery pressure ≥25 mm Hg or pulmonary vascular resistance (PVR) > 400 dyn‧s‧cm−5 based on right heart catheterization were randomized to treatment with PADN (PADN group; n = 25) using remote magnetic navigation for ablation or medical therapy with riociguat (MED group; n = 25). In the MED group, a sham procedure with mapping but no ablation was performed. The primary endpoint was PVR at 12 months after randomization. Key secondary endpoint included 6-min walk test. Results After PADN procedure, 2 patients (1 in each group) developed groin hematoma that resolved without any consequences. At 12 months, mean PVR reduction was 258 ± 135 dyn‧s‧cm−5 in the PADN group versus 149 ± 73 dyn‧s‧cm−5 in the MED group, mean between-group difference was 109 dyn‧s‧cm−5 (95% confidence interval: 45 to 171; p = 0.001). The 6-min walk test distance was significantly increased in the PADN group as compared to distance in the MED group (470 ± 84 m vs. 399 ± 116 m, respectively; p = 0.03). Conclusions PADN in patients with residual CTEPH resulted in substantial reduction of PVR at 12 months of follow-up, accompanied by improved 6-min walk test.

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering. In a new strategy for increasing the availability of lungs for transplantation, human lungs declined for transplantation because of their poor quality can be recuperated by connecting them to the circulation of a pig.

The pathogenesis of colorectal cancer (CRC) is closely associated with the development of an antitumor immune response. An important role in the regulation of the immune response is given to regulatory T cells (Treg), which may interfere with the effective recognition and elimination of tumor cells. The aim of the work was to study the content of peripheral CD8+Treg cells in patients with CRC. Analysis of the membrane and intracellular expression of markers was performed by multicolor flow cytometry. In patients with CRC, an accumulation of peripheral CD8+ and CD4+Treg lymphocytes was observed at all stages of CRC. Along with this, there was a significant decrease in the number of activated T-helpers.

Based on the study of recent scientific literature devoted to neovascularization and angiogenesis in malignant neoplasms, it was concluded that there are many publications on each of the problems of tumor angiogenesis and vascularization. The formation of blood vessels in a tumor and certain aspects of the prognostic value of the severity of vascularization in almost all forms of cancer are considered. Special attention is paid to the peculiarities of angiogenesis in tumors of the female reproductive system. A large number of vessels in the tumor often indicates a poor prognosis. The influence of various factors on the initiation of angiogenesis and the process itself, as well as the possibility of suppressing such signals to slow down the formation of blood vessels and thus the development of the tumor are widely studied. The results of pharmacological suppression of tumor vessel formation demonstrate a good clinical outcome but one accompanied by a large number of severe adverse side effects. Such a significant amount of studies on each of the problems of tumor vascularization indicates the increasing importance of this area of oncology. At the same time, only a very small number of works are devoted to the study of the differences in angiogenesis and number of vessels between different parts of the tumor, as well as between the primary tumor node and its metastases. The refinement of the results is still to be done. It was noted that the expression of proangiogenic factors in metastases is usually higher than in the source of metastasis, and the expression in lymphogenous metastases is higher than in hematogenous ones.

Catheter navigation and 3-dimensional (3D) cardiac mapping are essential components of minimally invasive electrophysiological procedures.The purpose of this study was to develop a novel 3D mapping system (KODEX - EPD, EPD Solutions, Best, The Netherlands) that measures changing electric field gradients induced on intracardiac electrodes to enable catheter localization and real-time 3D cardiac mapping.We first validated the accuracy of the system's measurement and localization capabilities by comparing known and KODEX - EPD-measured distances and locations at 12 anatomical landmarks in both the atria and ventricles of 4 swine. Next, in vivo images of 3D porcine cardiac anatomy generated by KODEX - EPD and widely used CARTO 3 system (Biosense Webster, Inc., Diamond Bar, CA) were compared with gold standard computed tomography images acquired from the same animals. Finally, 3D maps of atrial anatomy were created for 22 patients with paroxysmal atrial fibrillation (Dielectric Unravelling of Radiofrequency ABLation Effectiveness trial).First, the mean error between known and measured distances was 1.08 ± 0.11 mm (P.01) and the overall standard deviation between known and measured locations in 12 areas of the porcine heart was 0.35 mm (P.01). Second, an expert comparison of 3D image quality revealed that KODEX - EPD is noninferior to CARTO 3. Third, the system enabled 3D imaging of atrial anatomy in humans, provided real-time images of atrioventricular valves, and detected important anatomical variations in a subset of patients.The KODEX - EPD system is a novel 3D mapping system that accurately detects catheter location and can generate high-resolution images without the need for preacquired imaging, specialty catheters, or a point-by-point mapping procedure.

The paper addresses V. Brusov-K. Balmont confusing relationship. The author cites the two poets’ correspondence, and V. Brusov’s verse «Ему же» (To Him) addressed to K. Balmont. The analysis reveals the two writers’ divergent approach to the notions of poetry and poetic skills.

The paper is devoted to the analysis of the problem of determining the source code author , which is of interest to researchers in the field of information security, computer forensics, assessment of the quality of the educational process, protection of intellectual property. The paper presents a detailed analysis of modern solutions to the problem. The authors suggest two new identification techniques based on machine learning algorithms: support vector machine, fast correlation filter and informative features; the technique based on hybrid convolutional recurrent neural network. The experimental database includes samples of source codes written in Java, C ++, Python, PHP, JavaScript, C, C # and Ruby. The data was obtained using a web service for hosting IT-projects – Github. The total number of source codes exceeds 150 thousand samples. The average length of each of them is 850 characters. The case size is 542 authors. The experiments were conducted with source codes written in the most popular programming languages. Accuracy of the developed techniques for different numbers of authors was assessed using 10-fold cross-validation. An additional series of experiments was conducted with the number of authors from 2 to 50 for the most popular Java programming language. The graphs of the relationship between identification accuracy and case size are plotted. The analysis of result showed that the method based on hybrid neural network gives 97% accuracy, and it’s at the present time the best-known result. The technique based on the support vector machine made it possible to achieve 96% accuracy. The difference between the results of the hybrid neural network and the support vector machine was approximately 5%.

Background Expression of the Receptor for Advanced Glycation Endproducts (RAGE) initiates pro-inflammatory pathways resulting in lung destruction. We hypothesized that RAGE directed imaging demonstrates increased lung uptake in smoke-exposure. Methods After exposure to room air or to cigarette smoke for 4-weeks or 16-weeks, rabbits were injected with 99mTc-anti-RAGE F(ab’)2 and underwent Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging. Lung radiotracer uptake was calculated as percent injected dose (%ID). Lungs were dissected for gamma well counting and histological analysis. Results 99mTc-anti-RAGE F(ab’)2 SPECT/CT imaging demonstrated increased lung expression of RAGE with smoke exposure compared to room air control at 4-weeks: Room air right (R) 0.75 ± 0.38%ID, left (L) 0.62 ± 0.32%ID vs. Smoke exposed R 0.17 ± 0.03, L 0.17 ± 0.02%ID (p = 0.02 and 0.028, respectively). By 16-weeks of smoke exposure, the uptake decreased to 0.19 ± 0.05%ID R and 0.17 ± 0.05%ID L, significantly lower than 4-week imaging (p = 0.0076 and 0.0129 respectively). Staining for RAGE confirmed SPECT results, with the RAGE ligand HMGB1 upregulated in the macrophages of 4-week smoke-exposed rabbits. Conclusions RAGE-directed imaging identified pulmonary RAGE expression acutely in vivo in an animal model of emphysema early after smoke exposure, with diminution over time. These studies document the extent and time course of RAGE expression under smoke exposure conditions and could be utilized for disease monitoring and examining response to future RAGE-targeted therapies. Electronic supplementary material The online version of this article (10.1186/s12931-019-1064-4) contains supplementary material, which is available to authorized users.

The number of available donor organs limits lung transplantation, the only lifesaving therapy for the increasing population of patients with end-stage lung disease. A prevalent etiology of injury that renders lungs unacceptable for transplantation is gastric aspiration, a deleterious insult to the pulmonary epithelium. Currently, severely damaged donor lungs cannot be salvaged with existing devices or methods. Here we report the regeneration of severely damaged lungs repaired to meet transplantation criteria by utilizing an interventional cross-circulation platform in a clinically relevant swine model of gastric aspiration injury. Enabled by cross-circulation with a living swine, prolonged extracorporeal support of damaged lungs results in significant improvements in lung function, cellular regeneration, and the development of diagnostic tools for non-invasive organ evaluation and repair. We therefore propose that the use of an interventional cross-circulation platform could enable recovery of otherwise unsalvageable lungs and thus expand the donor organ pool., Gastric aspiration severely injures donor lungs, frequently making them unacceptable for transplantation. Here the authors show that an interventional cross-circulation platform enables the regeneration of severely damaged lungs in a swine model of gastric aspiration injury.

Introduction: A novel cardiac gamma camera utilizes the radiopharmaceutical Iodine-123-Meta-iodobenzylguanidine (123I-MIBG) to visualize cardiac sympathetic innervation. Physiological accumulation of123I-mIBG provides an anatomical quantitative determination of the structures of the autonomic nervous system (ANS) with discrete uptake areas (DUA) of sympathetic activity located in the left atrium (LA) corresponding to the main ganglionic plexi (GP) clusters that could not previously be visualized.Aim: to visualize the DUA of the heart in patients with paroxysmal atrial fibrillation (AF) and to assess the effect of radiofrequency ablation (RFA) on DUA in LA.Materials and Methods. Computed tomography (CT) of the heart and radionuclide imaging with123I-mIBG were performed in 15 patients with paroxysmal AF. The results of the study were combined with preliminary taken CT images to create a detailed anatomical map of the sympathetic activity of the heart. The processed images were combined with the 3D reconstruction of the LA, obtained with the navigation system (CARTO 3, CARTO RMT). In DUA, high-frequency stimulation (HFS) followed by RF ablation was performed using the current recommended parameters.Results. Forty-eight DUA (median 3 [3; 3]) were identified. Average activity of DUA was 1315 [1171; 1462] cnt / sec / ml. Positive response to HFS in the DUA was obtained in 8 (53.3 %) patients. Prior to ablation, no response was received to HFS in areas of LA outside the DUA. After ablation, there was no response to HFS in the DUA sites. At repeated scans 3 DUA (median 0 [0; 0]; pConclusion. In patients with AF, the areas of sympathetic activity in LA can be visualized by physiological localized uptake of123I-mIBG. Radiofrequency catheter ablation can target the identified sympathetic innervation structures in AF patients precisely and effectively.

ObjectivesThe association between obesity and atrial fibrillation (AF) is well-established. We aimed to evaluate the impact of index body mass index (BMI) on AF recurrence at 12 months following catheter ablation using propensity-weighted analysis. In addition, periprocedural complications and fluoroscopy details were examined to assess overall safety in relationship to increasing BMI ranges.MethodsBaseline, periprocedural and follow-up data were collected on consecutive patients scheduled for AF ablation. There were no specific exclusion criteria. Patients were categorised according to baseline BMI in order to assess the outcomes for each category.ResultsAmong 3333 patients, 728 (21.8%) were classified as normal (BMI 2), 1537 (46.1%) as overweight (BMI 25.5–29.0 kg/m2) and 1068 (32.0%) as obese (BMI ≥30.0 kg/m2). Procedural duration and radiation dose were higher for overweight and obese patients compared with those with a normal BMI (p=0.002 and p2led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429; p=0.011), while no significant correlation was found between overweight and normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112).ConclusionsPatients with a baseline BMI ≥30 kg/m2have a higher recurrence rate of AF following catheter ablation and therefore lifestyle modification to target obesity preprocedure should be considered in these patients.

The problems of chronic or noncommunicable diseases (NCD) that now kill around 40 million people each year require multiparametric combinatorial diagnostics for the selection of effective treatment tactics. This could be implemented using the biosensor principle based on peptide aptamers for spatial recognition of corresponding protein markers of diseases in biological fluids. In this paper, a low-cost label-free principle of biomarker detection using a biosensor system based on fluorometric registration of the target proteins bound to peptide aptamers was investigated. The main detection principle considered includes the re-emission of the natural fluorescence of selectively bound protein markers into a longer-wavelength radiation easily detectable by common charge-coupled devices (CCD) using a specific luminophore. Implementation of this type of detection system demands the reduction of all types of stray light and background fluorescence of construction materials and aptamers. The latter was achieved by careful selection of materials and design of peptide aptamers with substituted aromatic amino acid residues and considering troponin T, troponin I, and bovine serum albumin as an example. The peptide aptamers for troponin T were designed in silico using the «Protein 3D» (SPB ETU, St. Petersburg, Russia) software. The luminophore was selected from the line of ZnS-based solid-state compounds. The test microfluidic system was arranged as a flow through a massive of four working chambers for immobilization of peptide aptamers, coupled with the optical detection system, based on thick film technology. The planar optical setup of the biosensor registration system was arranged as an excitation-emission cascade including 280 nm ultraviolet (UV) light-emitting diode (LED), polypropylene (PP) UV transparent film, proteins layer, glass filter, luminophore layer, and CCD sensor. A laboratory sample has been created.

To investigate the relationship between epicardial adipose tissue (EAT) volume and distribution and the parameters of global cardiac and regional left atrial (LA) sympathetic activity in patients with atrial fibrillation (AF).The data of the 45 consecutive patients scheduled for an index catheter ablation (CA) for AF were analyzed. Total and peri-atrial EAT volumes were measured by cardiac CT. Parameters of global cardiac sympathetic activity and discrete sympathetic regions around LA were assessed byPeri-atrial EAT volume is associated with regions of sympathetic activity corresponding to typical anatomical locations of LA GP. The WR was associated with reduced risk of AF recurrence while LV myocardial SDS was linked to increased hazards of AF recurrence.