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Background: Resting full-cycle ratio (RFR) is an alternative to fractional flow reserve (FFR) for the evaluation of borderline coronary artery lesions. Although FFR and RFR results are discordant in some cases, factors associated with the discordance remain unclear. The role of coronary microvascular dysfunction (CMD) is discussed as a potential mechanism to explain these discrepancies., Aim: The study aimed to assess concordance between RFR and FFR in a real-life cohort from a high-volume center regarding the role of CMD., Methods: Consecutive patients with borderline coronary lesions undergoing coronary functional testing for chronic coronary syndromes were included in the study. Measurements of RFR and FFR were performed alongside additional coronary flow reserve (CFR), resistance reserve ratio (RRR), and an index of microcirculatory resistance (IMR) measurements. CMD was defined according to the current guideline by either IMR ≥25 or CFR ≤2.0 in vessels with no significant stenosis., Results: Measurements were performed in 157 coronary arteries, in 101 patients, with a median age of 66 y., 74% male, with prior history of arterial hypertension (96%), dyslipidaemia (91%), and diabetes (40%). The median value of vessel diameter stenosis was 45% according to QCA.Overall, FFR and RFR values were significantly correlated ( r = 0.66, p < 0.001), where positive FFR/negative RFR and negative FFR/positive RFR were observed in 6 (3.8%) and 38 (24.2%) of 157 vessels. The RFR/FFR discrepancy was present in 44 (28%) of measurements. CMD was confirmed in 28 (64%) of vessels with discrepant RFR/FFR and in 46 (41%) of vessels with concordant results ( p = 0.01). In discordant RFR/FFR vessels, as compared to concordant ones, significantly lower values of CFR [median 1.95 (IQR: 1.37, 2.30) vs. 2.10 (IQR: 1.50, 3.00), p = 0.030] and RRR [median 2.50 (IQR: 1.60, 3.10) vs. 2.90 IQR (1.90, 3.90), p = 0.048] were observed.Main predictors of RFR/FFR discrepancy in a univariate regression analysis were: higher age of patients [OR = 1.06 (1.01; 1.10), p = 0.010], presence of CMD [OR = 2.51 (1.23; 5.25), p = 0.012], lower CFR [OR = 1.64 (1.12; 2.56), p = 0.018], and lower RRR values [OR = 1.35 (95% CI: 1.03; 1.83), p = 0.038]., Conclusion: In discrepant RFR/FFR vessels, CMD is more prevalent than in concordant RFR/FFR measurements, which can be driven by lower CFR or RRR values. Further research is needed to confirm this observation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Legutko, Niewiara, Guzik, Szolc, Podolec, Nosal, Diachyshyn, Zmudka and Kleczynski.)

Competing Interests: Conflict of interest: Authors have no conflict of interest.

Non-obstructive coronary artery disease occurs in 3.5-15% of patients presenting with acute myocardial infarction. This group of patients has a poor prognosis. Identification of factors that predict worse outcomes in myocardial infarction with non-obstructive coronary arteries (MINOCA) is therefore important. Patients with a diagnosis of MINOCA ( n = 110) were enrolled in this single-center, retrospective registry. Follow-up was performed 12, 24 and 36 months after discharge. The primary composite endpoint was defined as myocardial infarction, coronary revascularization, stroke or TIA, all-cause death, or hospital readmission due to any cardiovascular event. The mean age of the study group was 64.9 (± 13.5) years and 38.2% of patients were male. The occurrence of the primary composite endpoint was 36.4%. In a COX proportional hazards model analysis, older age ( p = 0.027), type 2 diabetes ( p = 0.013), history of neoplasm ( p = 0.004), ST-segment depression ( p = 0.018) and left bundle branch block/right bundle branch block ( p = 0.004) by ECG on discharge, higher Gensini score ( p = 0.022), higher intraventricular septum ( p = 0.007) and posterior wall thickness increases ( p = 0.001) were shown to be risk factors for primary composite endpoint occurrence. Our study revealed that several factors such as older age, type 2 diabetes, ST-segment depression and LBBB/RBBB in ECG on discharge, higher Gensini score, and myocardial hypertrophy and history of neoplasm may contribute to worse clinical outcomes in MINOCA patients.

Introduction: Inflammation plays a pivotal role in blood pressure regulation. Data on experimental models of hypertension and hypertensive patients reflect the imbalance between T regulatory (Treg) and Th17 effector cells (Th17)., Objectives: The aim of this study was to quantify peripheral blood Treg lymphocytes and Th17 subsets in individuals with primary hyperaldosteronism (PHA) and resistant hypertension (RHT) presenting with elevated blood pressure levels and augmented cardiovascular risk when compared with normotensive controls (CTRL)., Patients and Methods: Twenty CTRL participants, 21 patients with PHA, and 20 patients with RHT were enrolled. Plasma renin and angiotensin II, serum aldosterone concentration, ambulatory blood pressure monitoring (ABPM), echocardiography, clinical data, and phenotype of peripheral blood cells were assessed., Results: There were no statistically significant differences in terms of age and sex between the groups. Similar systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in ABPM were observed in individuals with PHA and RHT. PHA patients had lower angiotensin II and 4‑fold higher aldosterone concentrations than CTRL patients. Both, PHA and RHT were associated with cardiac hypertrophy and coronary artery disease. RHT patients presented a significantly higher CD4+IL‑17A+ T cell number when compared with PHA and CTRL ones. The number of CD4+CD25+FOXP3+ T cells did not differ between patients with secondary hypertension and normotensive controls. Finally, positive correlations between the data on 24 h SBP and the content of CD4+IL‑17A+ and CD4+CD25+FOXP3+ in the PHA were found., Conclusions: Elevated 24 h SBP in PHA was associated with the increased numbers of CD4+IL‑17 and CD4+CD25+FOXP3+ T cells.

Rationale: Guidelines of rare synchronous tumours treatment are often unavailable due to lack of wide prospective studies. Additionally, their management is not just a simple sum of coexisting tumours management and has to regard many circumstances like symptoms, age, comorbidities, advancement., Patient Concerns: Herein, we report a case of an 81-year-old woman who presented with bleeding from the prolapsed uterus., Diagnoses: Based on physical examination, that is, speculum examination, bimanual, and per rectum, followed by rectoscopy and histopathology, the diagnosis of cervical squamous cell carcinoma FIGO IIA2 in prolapsed uterus with anal canal adenocarcinoma cT1N0M0 was made., Interventions: Dominating complaint of bleeding from prolapsed cervix was managed with radical vaginal hysterectomy in conjunction with wide colpectomy preceded by laparoscopic pelvic and paraaortic lymphadenectomy. Due to the lack of consent for removal of the anus, only radiotherapy was applied instead., Outcomes: The patient underwent magnetic resonance image follow-up. No recurrence was found at 18 months., Lessons: Imaging is useful method of synchronous cancers diagnostics. These cancers may vary in aetiology and stage. Cervical cancer may be co-existing with another anogenital cancer. Therapy of synchronous cancers should be individualized taking into account patient's consent, age, physical condition, and comorbidities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study's primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon., Methods: Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) < 60 mmHg) combined with a high inotrope score (> 10). Data for long-term mortality were obtained from the population registration office., Results: PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) μg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) μg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034)., Conclusions: Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients., (© 2021. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: Survival after heart transplantation (HTX) is extended due to continuous improvement of medical care, allowing enough time for coronary artery vasculopathy to develop. Data on the clinical outcome of cardiac transplantation patients after percutaneous coronary intervention (PCI) are still not extensively explored. The aim of our study was to assess whether heart transplantation itself compromises the outcome in patients undergoing percutaneous coronary intervention and to assess survival rates as well as major cardiovascular complications in heart transplant recipients who had undergone PCI., Material and Methods: Thirty-three heart transplant recipients who had undergone PCI in the years 2005 to 2015 in a single center were matched by age, sex and main risk factors of arteriosclerosis with 33 controls without heart transplant history. Mean age of patients was 54.6 ±11.4 years in the HTX group and 58.8 ±10.8 years in controls. Median time from heart transplant to PCI was 13 years (4.4-22 years). Case and control groups did not differ in terms of standard risk factors of coronary artery disease, apart from chronic kidney disease, which was present in 70% of patients after heart transplantation, and dyslipidemia, which was present in 91% of control subjects., Results: Patients after HTX had worse survival compared to controls ( p = 0.04). When adjusted for comorbidities in the Cox regression model, there was no significant difference in survival between cardiac transplant recipients and the control group (HR = 1.06; 95% CI: 0.10-11.24). Chronic renal disease was a significant predictor of all-cause mortality (HR = 29.9; 95% CI: 2.3-393). Considering other endpoints, HTX patients had considerably higher incidence of severe bleeding compared to the control group (27% vs. 3%, p < 0.05)., Conclusions: There was no significant difference in myocardial infarction rate, revascularization or hospitalization rates., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia & Banach.)

Objective: Introduction: Index of microcirculatory resistance assessment is an invasive method of measuring coronary microcirculation function. Association between impaired microcirculatory function and higher rate of cardiovascular events was proven. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio seem to be a promising parameters to predict coronary microcirculatory disease in patients with chronic coronary syndrome. The aim: To determine neutrophil-lymphocyte ratio and platelet-lymphocyte ratio levels in patients with coronary microcirculatory disease and potential association with clinical outcome., Patients and Methods: Material and methods: 82 consecutive patients with mean age of 67 years, 67% male, were tested for presence of coronary microcirculatory disease using index of microcirculatory resistance. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were calculated based on admission full blood count. Follow-up with major adverse cardiac and cardiovascular events registration was performed (median 24 months)., Results: Results: The study showed significantly higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with coronary microcirculatory disease compared to control group (3.58±2.61 vs 2.54±1.09 and 164±87.9 vs 124±36.6 respectively). Higher level of platelet-lymphocyte ratio in patients with coronary microcirculatory disease results in worse MACCE-free survival. Optimal cut-off values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio to detect coronary microcirculatory disease were 3.2 and 181.3, respectively., Conclusion: Conclusions: Higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with increased index of microcirculatory resistance value. Platelet-lymphocyte ratio may be used as a predictor of worse outcome in patients with coronary microcirculatory disease.

Introduction: Long and diffuse coronary lesions (LDCLs) are routinely subjected to percutaneous management, but long‑term clinical outcomes and complication predictors with the use of contemporary stents and techniques remain undetermined., Objectives: The aim of the study was to address long‑term effects of percutaneous management of LDCLs, using contemporary devices and optimization techniques., Patients and Methods: Long and diffuse coronary lesion was defined as a lesion requiring an implantation of 30 mm or longer total stent(s) length (TSL) into one coronary artery (bailouts excluded). There were 290 LDCL interventions with the use of newer generation drug‑eluting stents (DESs; cobalt chromium everolimus- or zotarolimus-eluting stents) performed between January 2013 and January 2016., Results: The mean (SD) TSL was 55.5 (16.8) mm. The use of intravascular ultrasound / optical coherence tomography was 17.1%, rotablation, 6.9%, and noncompliant balloon, 88.9%. The median (range) follow‑up duration was 831 (390-1373) days. All‑cause mortality and cardiac death rates were 11.7% and 6.9%, respectively. The myocardial infarction (MI) rate was 6.6%, including target‑vessel MI in 4.1%. The rate of clinically‑driven repeat revascularization was 13.8%, and of definite or probable LDCL stent thrombosis, 7.2%. Overall patient‑oriented adverse event rate (any death, MI, or repeat revascularization) was 25.5%, and device‑oriented rate (cardiac death, target vessel‑MI, or target lesion restenosis), 13.4%. Adverse outcome predictors were chronic kidney disease, acute coronary syndrome as an indication for the procedure, chronic heart failure with reduced left ventricular ejection fraction, multivessel disease, and coexisting peripheral artery disease, but not lesion‑related factors, such as bifurcation, calcification, chronic total occlusion, or TSL., Conclusions: Adverse outcomes following contemporary LDCL management using newer generation DESs in routine clinical practice are associated with clinical patient characteristics rather than lesion characteristics or TSL. We identified high‑risk patient cohorts that may benefit from enhanced surveillance.

INTRODUCTION Air pollution is reaching alarming proportions worldwide; however, previous studies concerning the association between air pollution and myocardial infarction (MI) provided conflicting results. OBJECTIVES We evaluated a relationship between short‑term fluctuations in outdoor particulate matter (PM) and nitrogen dioxide (NO2) levels and the number of hospitalizations due to MI among the inhabitants of Kraków, Poland. PATIENTS AND METHODS Data on hospitalizations, daily pollutant concentrations, infections, and meteorological parameters were collected from December 2012 to September 2015. Data were assessed using a time‑series regression analysis with a distributed lag model. RESULTS An increase of 10 μg/m3 in PM2.5 levels was associated with a higher risk of hospital admission due to MI (odds ratio [OR], 1.32; 95% CI, 1.01-1.40; P = 0.0002). For PM10 the effect was observed only with a simultaneous decrease of 1ºC in the mean daily temperature (OR, 1.08; 95% CI, 1.01-1.17; P = 0.03). Significant effects were observed at lags 5 and 6. The effect of NO2 was significant at lags 0 and 1, but only in patients aged 70 years or older (OR, 1.13; 95% CI, 1.01-1.23; P = 0.007) and those with pulmonary disorders (OR, 1.12; 95% CI, 1.01-1.31; P = 0.01). CONCLUSIONS In all age groups, the short‑term elevation in PM2.5 levels was associated with an increased number of daily hospital admissions for MI, whereas for PM10 the effect was significant only with a simultaneous decrease in temperature. The effect of NO2 was observed only in older individuals and patients with pulmonary disorders. A negative clinical effect was more delayed in time in the case of exposure to PM than to NO2.

INTRODUCTION    Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. OBJECTIVES    We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). PATIENTS AND METHODS    The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor 1α (SDF1α), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. RESULTS    Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and SDF1α levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between SDF1α and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. CONCLUSIONS    Circulating ADMA levels indicate medial arterial calcification in patients with CKD.

Our ability to predict the identity of future invasive alien species is largely based upon knowledge of prior invasion history. Emerging alien species-those never encountered as aliens before-therefore pose a significant challenge to biosecurity interventions worldwide. Understanding their temporal trends, origins, and the drivers of their spread is pivotal to improving prevention and risk assessment tools. Here, we use a database of 45,984 first records of 16,019 established alien species to investigate the temporal dynamics of occurrences of emerging alien species worldwide. Even after many centuries of invasions the rate of emergence of new alien species is still high: One-quarter of first records during 2000-2005 were of species that had not been previously recorded anywhere as alien, though with large variation across taxa. Model results show that the high proportion of emerging alien species cannot be solely explained by increases in well-known drivers such as the amount of imported commodities from historically important source regions. Instead, these dynamics reflect the incorporation of new regions into the pool of potential alien species, likely as a consequence of expanding trade networks and environmental change. This process compensates for the depletion of the historically important source species pool through successive invasions. We estimate that 1-16% of all species on Earth, depending on the taxonomic group, qualify as potential alien species. These results suggest that there remains a high proportion of emerging alien species we have yet to encounter, with future impacts that are difficult to predict., Competing Interests: The authors declare no conflict of interest.

Species distribution models are scarcely applicable to invasive species because of their breaking of the models' assumptions. So far, few mechanistic, semi-mechanistic or statistical solutions like dispersal constraints or propagule limitation have been applied. We evaluated a novel quasi-semi-mechanistic approach for regional scale models, using historical proximity variables (HPV) representing a state of the population in a given moment in the past. Our aim was to test the effects of addition of HPV sets of different minimal recentness, information capacity and the total number of variables on the quality of the species distribution model for Heracleum mantegazzianum on 116000 km2 in Poland. As environmental predictors, we used fragments of 103 1×1 km, world- wide, free-access rasters from WorldGrids.org. Single and ensemble models were computed using BIOMOD2 package 3.1.47 working in R environment 3.1.0. The addition of HPV improved the quality of single and ensemble models from poor to good and excellent. The quality was the highest for the variants with HPVs based on the distance from the most recent past occurrences. It was mostly affected by the algorithm type, but all HPV traits (minimal recentness, information capacity, model type or the number of the time periods) were significantly important determinants. The addition of HPVs improved the quality of current projections, raising the occurrence probability in regions where the species had occurred before. We conclude that HPV addition enables semi-realistic estimation of the rate of spread and can be applied to the short-term forecasting of invasive or declining species, which also break equal-dispersal probability assumptions.

Although research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations across regions and taxa. Using a novel database of 45,813 first records of 16,926 established alien species, we show that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970-2014). Inter-continental and inter-taxonomic variation can be largely attributed to the diaspora of European settlers in the nineteenth century and to the acceleration in trade in the twentieth century. For all taxonomic groups, the increase in numbers of alien species does not show any sign of saturation and most taxa even show increases in the rate of first records over time. This highlights that past efforts to mitigate invasions have not been effective enough to keep up with increasing globalization.

The knotweed taxa Fallopia japonica, F. sachalinensis and their interspecific hybrid F. × bohemica are some of the most aggressive invaders in Europe and North America and they are serious threats to native biodiversity. At the same time, they constitute a unique model system for the creation of hybrids and studies of the initiation of evolutionary processes. In the presented study, we focused on (i) examining genetic diversity in selected populations of three Fallopia taxa in the invaded (Poland) and native ranges (Japan), (ii) establishing genome size and ploidy levels and (iii) identifying ribosomal DNA (rDNA)-bearing chromosomes in all of the taxa from the invaded range. We found that the genetic diversity within particular taxa was generally low regardless of their geographical origin. A higher level of clonality was observed for the Polish populations compared to the Japanese populations. Our study suggests that the co-occurrence of F. sachalinensis together with the other two taxa in the same stand may be the source of the higher genetic variation within the F. × bohemica hybrid. Some shift towards the contribution of F. japonica alleles was also observed for selected F. × bohemica individuals, which indicates the possibility of producing more advanced generations of F. × bohemica hybrids. All of the F. sachalinensis individuals were hexaploid (2n = 6x = 66; 2C = 6.01 pg), while those of F. japonica were mostly octoploid (2n = 8x = 88; 2C = 8.87 pg) and all of the F. × bohemica plants except one were hexaploid (2n = 6x = 66; 2C = 6.46 pg). Within the chromosome complement of F. japonica, F. sachalinensis and F. × bohemica, the physical mapping of the rDNA loci provided markers for 16, 13 and 10 chromosomes, respectively. In F. × bohemica, a loss of some of rDNA loci was observed, which indicates the occurrence of genome changes in the hybrid., Competing Interests: The authors have declared that no competing interests exist.

Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES(-/-) knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES(-/-)), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8(+) and double-negative CD3(+)CD4(-)CD8(-) T cells in perivascular space and reduced vascular oxidative stress while FoxP3(+) T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = -0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.-Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension., (© The Author(s).)

Cardiovascular diseases, and in particular coronary artery disease (CAD), are the leading causes of death in Europe and represent around 50% of overall mortality. Numerous cardiovascular markers have been proposed in relation to cardiovascular risk prediction, in relation to cardiac and vascular and cerebral events. Chemokines which regulate immune cell vascular chemotaxis, including CCL5/RANTES are points of great interest. We hypothesized that chemokine RANTES level measured in peripheral blood may be associated with severity of atherosclerosis in patients with stable angina undergoing coronary angiography. RANTES and interleukin 18 (IL-18) levels were measured by ELISA. Classical and novel cardiovascular risk factors like brachial flow mediated dilation and intima-media thickness were analyzed in the context of chemokine levels and severity of atherosclerosis. Study included 62 consecutive patients with coronary atherosclerosis demonstrated by coronary angiography, (mean age 59.3 years (S.D. = 7.4)), divided into two groups: group I with lower severity of atherosclerosis, (n = 45) and group 2 with severe CAD (n = 17) based on coronary angiography. Groups were well balanced for classic risk factors for atherosclerosis. Mean RANTES level were significantly higher in patients in group I (67.9 ng/ml, S.E.M. = 3.97) than in group II (50.5 ng/ml, S.E.M. = 7.49; P = 0.03). In contrast, IL-18 levels were similar in both groups (255 pg/ml in group I and 315 pg/ml, S.E.M. = 40.91 in group I, P = 0.12), as well as hsCRP concentration (3.45 S.E.M. = 2.66 ng/ml and 4.69 ng/ml S.E.M.= 1.64 ng/ml respectively; P = 0.47). Flow-mediated dilatation (FMD) values have been significantly lower in group II than in group I (6.31; S.E.M. = 0.61; vs 4.41; S.E.M. = 0,56, respectively, P = 0.026), while nitroglycerine-mediated dilatation (NMD) did not differ, indicating more pronounced endothelial dysfunction. No significant correlations between chemokine RANTES levels and intima-media thickness (IMT), FMD measurements have been found in the total population studied. Chemokine RANTES level could become a useful marker of severity of coronary artery disease. Its lower levels were observed in patients with more diffuse disease. Elevated level of chemokine RANTES in patients with stable angina pectoris may evaluate patients to high risk group in plaque formation at early stages of atherosclerosis.

Unlabelled: Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2(-)) production in human AAA., Methods and Results: AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n=16) than in risk factor matched controls (n=16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2(-) in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size., Conclusions: Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients., (Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

We compared the variance of area and diameter significant stenosis measurement between quantitative computed tomography coronary angiography (QCTA) and quantitative invasive coronary angiography (QCA). Fifty patients presenting 65 significant coronary artery stenoses (≥70% area stenosis) in QCTA and QCA were included. Spearman's rank correlation revealed that area stenosis measurement by QCTA and QCA yields higher correlation than diameter stenosis and is highest for noncalcified and mixed lesions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Morbidities related to atherosclerosis, such as acute coronary syndromes (ACS) including unstable angina and myocardial infarction, remain leading causes of mortality. Unstable plaques are inflamed and infiltrated with macrophages and T lymphocytes. Activated dendritic cells interact with T cells, yielding predominantly Th1 responses involving interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), while the role of interleukin 17 (IL-17) is questionable. The expansion of CD28nullCD4 or CD8 T cells as well as pattern recognition receptors activation (especially Toll-like receptors; TLR2 and TLR4) is characteristic for unstable plaque. Inflammation modifies platelet and fibrin clot characteristics, which are critical for ACS. Understanding of the inflammatory mechanisms of atherothrombosis, bridging inflammation, oxidative stress and immune regulation, will allow for the detection of subjects at risk, through the use of novel biomarkers and imaging techniques including intravascular ultrasound, molecular targeting, magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Moreover, understanding the specific inflammatory pathways of plaque rupture and atherothrombosis may allow for immunomodulation of ACS. Statins and anti-platelet drugs are anti-inflammatory, but importance of immune events in ACS warrants the introduction of novel, specific treatments directed either on cytokines, TLRs or inflammasomes. While the prime time for the introduction of immunologically inspired diagnostic tests and treatments for atherosclerosis have not come yet, we are closer than ever before to finally being able to benefit from this vast body of experimental and clinical evidence. This paper provides a comprehensive review of the role of the immune system and inflammation in ACS.

Introduction: Varicose vein disease is one of the most common morbidities in the developed countries. Recent studies have shown that oxidative stress is increased in varicose veins (VV) and venous insufficiency. However, the exact mechanisms of oxidative stress in VV remain unknown., Objectives: The aim of the study was to measure superoxide anion production and analyze its enzymatic sources in VV in comparison with control human saphenous veins (HSV). Superoxide production was also compared between the proximal and distal segments of the veins., Patients and Methods: Proximal and distal segments of varicose veins (14 patients, aged 52 ±3.5 years) and control veins (15 patients, aged 56 ±4 years) were obtained during VV removal or elective coronary artery bypass graft surgery, respectively. Subjects were matched for age, sex, and the major risk factors for atherosclerosis. Superoxide was measured by lucigenin-enhanced chemiluminescence (5 μmol/l) in the presence and absence of oxidase inhibitors., Results: Superoxide production was increased in VV compared with control HSV. This increase was particularly evident in the distal segments of VV. There was a significant correlation between superoxide production in the proximal and distal segments of HSV but not of VV. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and uncoupled nitric oxide synthase (NOS) were the major sources of superoxide in VV, because their inhibitors greatly attenuated superoxide production in VV., Conclusions: NADPH oxidases and NOS could represent valuable drug targets for pharmacological treatment and prevention of varicose vein disease. Oxidative stress may provide a link between endothelial dysfunction, inflammation, and immune activation and the development of chronic venous dysfunction.

Objectives: This study sought to examine the expression and activity of the calcium-dependent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in human atherosclerotic coronary arteries., Background: The NOX-based NADPH oxidases are major sources of reactive oxygen species (ROS) in human vessels. Several NOX homologues have been identified, but their relative contribution to vascular ROS production in coronary artery disease (CAD) is unclear; NOX5 is a unique homolog in that it is calcium dependent and thus could be activated by vasoconstrictor hormones. Its presence has not yet been studied in human vessels., Methods: Coronary arteries from patients undergoing cardiac transplantation with CAD or without CAD were studied; NOX5 was quantified and visualized using Western blotting, immunofluorescence, and quantitative real-time polymerase chain reaction. Calcium-dependent NADPH oxidase activity, corresponding greatly to NOX5 activity, was measured by electron paramagnetic resonance., Results: Both Western blotting and quantitative real-time polymerase chain reaction indicated a marked increase in NOX5 protein and messenger ribonucleic acid (mRNA) in CAD versus non-CAD vessels. Calcium-dependent NADPH-driven production of ROS in vascular membranes, reflecting NOX5 activity, was increased 7-fold in CAD and correlated significantly with NOX5 mRNA levels among subjects. Immunofluorescence showed that NOX5 was expressed in the endothelium in the early lesions and in vascular smooth muscle cells in the advanced coronary lesions., Conclusions: These studies identify NOX5 as a novel, calcium-dependent source of ROS in atherosclerosis.

Introduction: The PIA2 allele is present in about 20-30% of European population. This allele has been associated with resistance to the antithrombotic action of aspirin in healthy PIA2 carriers., Objectives: To evaluate the functional association of the PIA1/A2 polymorphism of beta3 intergrins with increased thrombin generation and platelet activation in patients with coronary artery disease (CAD), treated with low-dose aspirin and whether the effect of this polymorphism is modulated by statin administration., Patients and Methods: In 31 patients (25 M, 6 F) with CAD, aged 47 to 76 years, the thrombin-antithrombin complex generation (TAT) and the soluble form of CD40 ligand level (sCD40L) in blood collected every 60 seconds at sites of standardized microvascular injury were determined., Results: Coronary angiography revealed > or = 1 major epicardial artery stenosis (> or = 50%) in all patients. Genotyping determined 18 subjects homozygous for PIA1 and 13 PIA2 heterozygous carriers. Homozygous PIA1 subjects exhibited increased fibrinogen levels compared with PIA2 carriers (4.2 [IQ 2.39] g/l vs. 2.5 [0.73] g/l, p <0.05). Maximal TAT level observed 6 min after microvascular injury was higher in PIA2 carriers (p = 0.01). Maximal sCD40L did not differ between PIA1/A1 subjects and PIA2 carriers. The PIA2 allele did not alter the velocity of TAT production and sCD40L release. The analysis of the area under the concentration vs. time curve for TAT revealed that PIA2 carriers exhibited increased thrombin generation compared with PIA1A1 subjects (by 17.5%, p <0.05). Subjects treated with statins (n = 12) had lower TAT generation and sCD40L release than non-treated (by 20%, p <0.005 and 23%, p <0.005, respectively). This effect was not altered by the PIA2 presence., Conclusions: In a model of microvascular injury the PIA1/A2 polymorphism influenced thrombin formation but not platelet activation in CAD patients treated with low-dose aspirin. The PIA2 allele did not alter the beneficial effect of statins on blood coagulation.

Background: Oxidative stress plays important role in the pathogenesis of atherosclerosis and coronary artery disease (CAD). We aimed to determine the sources and selected molecular mechanisms of oxidative stress in CAD., Methods and Results: We examined basal and NAD(P)H oxidase-mediated superoxide (O2*-) production using lucigenin chemiluminescence, ferricytochrome c and dihydroethidium fluorescence in human coronary arteries from 19 CAD and 17 non-CAD patients undergoing heart transplantation. NAD(P)H oxidase subunits and xanthine oxidase expression were measured. Superoxide production was greater in coronary arteries from patients with CAD, even in vessels without overt atherosclerotic plaques, and was doubled within branching points of coronary arteries. Studies using pharmacological inhibitors and specific substrates showed that NAD(P)H oxidases (60%) and xanthine oxidase (25%) are primary sources of O2*- in CAD. Losartan significantly inhibited superoxide production in coronary arteries. NAD(P)H oxidase activity and protein levels of the NADPH oxidase subunits p22phox, p67phox, and p47phox were significantly increased in CAD, as were mRNA levels for p22phox and nox2, and no NAD(P)H oxidase subunit mRNA levels correlated with NAD(P)H oxidase activity in vessels from individual patients. Activity and protein expression of xanthine oxidase were increased in CAD, whereas xanthine dehydrogenase levels were not changed., Conclusions: Increased expression and activity of NAD(P)H oxidase subunits and xanthine oxidase, in part mediated through angiotensin II and PKC-dependent pathways, are important mechanisms underlying increased oxidative stress in human coronary artery disease.

This study was designed to investigate changes in aggregability of red blood cells of patients with essential hypertension and concomitant hypercholesterolemia (total cholesterol level > 5.0 mmol/l) following the use of angiotensin converting enzyme inhibitors (ACE-I) along with or without inhibitor of reductase HMG-CoA (statin). Under standard pharmacotherapy (beta-receptor anatgonist, calcium chanel antagonist, and diuretic) aggregability of RBC in hypertensive patients was significantly increased in spite of the treatment. However, in patients receiving additionally ACE-I spontaneous aggregation of RBC was attenuated. We found that antihypertensive therapy consisting of ACE-I along with statin improved erythrocyte aggregation nearly to the level of normotensive and normocholesterolemic patients. Interestingly, this improvement of blood rheology was observed prior to statin-induced lowering of total cholesterol.

Acute right ventricular infarction (RVI) is usually caused by proximal occlusion of the right coronary artery. RVI is frequent, as it occurs in as many as one out of every two left ventricular interior and/or posterior wall infarctions. The involvement of the right ventricle in acute myocardial infarction has been shown to be associated with an increased risk of life-threatening arrhythmias and sudden cardiac death. Clinical course of RVI can vary from being completely silent to cardiogenic shock (seen in 10-15% patients with inferior wall infarction). RVI diagnosis is based on clinical signs (hypotension and increased jugular venous pressure while pulmonary fields are clear), ECG (ST elevation by > or = 1 mm in V4R), echocardiography (right ventricular wall regional motion abnormalities and/or right ventricle distension, paradoxical motion of the interventricular septum, tissue Doppler), technetium pyrophosphate scanning with ventriculography, and invasive patient monitoring. In addition to its important diagnostic part, the invasive patient monitoring plays a key role in risk stratification and can dynamically guide the treatment (such as fluid loading). In most cases, successful reperfusion in the infarct-related artery territory can be achieved by interventional management (i.e. angioplasty) or--if the latter is not available--by thrombolytic therapy. Patients with arterial hypotension require volume expansion which is best guided by the central venous pressure (CVP; a measure of the right atrial pressure, RAP) and the pulmonary capillary wedge pressure (PCWP). If the hemodynamics does not improve despite optimal fluid loading, pharmacological (catecholamine infusion) or mechanical (intra-aortic balloon pump) circulatory assistance needs to be implemented. Patients with significant sinus bradycardia or 3rd degree AV block may require temporary cardiac pacing. In addition, inhalatory nitric oxide (iNO) has been shown to reduce right ventricular afterload in a selective manner and its potential clinical role is currently being evaluated. Within several months after RVI, the right ventricular performance improves in most patients, including those without successful reperfusion of IRA. Such patients, however, have an increased risk of complications (including sudden death) while the recovery of right ventricular function is slow.

Between January 1995 and December 2000, 222 consecutive patients underwent complete aortic root replacement in the Department of Cardiovascular Surgery of the Hertz- und Gefaess- Klinik- Bad Neustadt (Germany). At the exception of 2 cases, all patients received the modified Bentallde Bono procedure with total excision of the ascending aorta and direct reimplantation of the coronary ostia using button technique. During the follow-up period of up to 6 years in 3 patients, a periprosthetic aneurysm was diagnosed. In two patients with clinical symptoms and a fistula between the prosthetic lumen and the spurium aneurysm, a reoperation was performed. Due to the complete absence of clinical symptoms or a fistula connecting the prosthesis and the aneurysm or progress in size of the aneurysm during the follow-up period the third patient was treated conservatively. The choice of proper treatment of this complication is difficult and should be based on continuous investigation of clinical symptoms and various technical examinations.

A case of a 62 year old male with acute type De Bakey I aortic dissection is presented. The ascending aorta, aortic valve and total aortic arch replacement were performed. Additionally the proximal descending aorta was replaced using elephant trunk technique, to close the entrance of the dissection. There was no patent false lumen in distal descending aorta in postoperative findings.

TAP, the human homologue of the yeast protein Mex67p, has been proposed to serve a role in mRNA export in mammalian cells. We have examined the ability of TAP to mediate export of Rev response element (RRE)-containing human immunodeficiency virus (HIV) RNA, a well-characterized export substrate in mammalian cells. To do this, the TAP gene was fused in frame to either RevM10 or RevDelta78-79. These proteins are nonfunctional Rev mutant proteins that can bind to HIV RNA containing the RRE in vivo but are unable to mediate the export of this RNA to the cytoplasm. However, the fusion of TAP to either of these mutant proteins gave rise to chimeric proteins that were able to complement Rev function. Significantly, cotransfection with a vector expressing NXT1 (p15), an NTF2-related cellular factor that binds to TAP, led to dramatic enhancement of the ability of the chimeric proteins to mediate RNA export. Mutant-protein analysis demonstrated that the domain necessary for nuclear export mapped to the C-terminal region of TAP and required the domain that interacts with NXT1, as well as the region that has been shown to interact with nucleoporins. RevM10-TAP function was leptomycin B insensitive. In contrast, the function of this protein was inhibited by DeltaCAN, a protein consisting of part of the FG repeat domain of CAN/Nup214. These results show that TAP can complement Rev nuclear export signal function and redirect the export of intron-containing RNA to a CRM1-independent pathway. These experiments support the role of TAP as an RNA export factor in mammalian cells. In addition, they indicate that NXT1 serves as a crucial cellular cofactor in this process.

Health estimation was performed in 134 patients (where 67% were women), aged 17-70, mean 42 years, 2-3 years after surgical correction of atrial septal defect type II (ASD II). The study consists of clinical examination and self-estimation of the quality of life with help of a mall questionnaire, with return ratio of 90%. The improvement of health status was declared by 80% of patients, where 23% stated considerable improvement. While 15% did not confirm any significant changes and 5% noticed worsening quality of life status (mainly connected with postoperative pain). The physical condition improved similarly, with range of tolerable physical effort doubled. The frequency of dyspnea, chest pain and palpitation decreased from 72%, 67% and 87% to 47%, 43% and 47%, respectively, as well as their intensity. More over, the frequency of anxiety decreased from 70% to 62% with reduction of its intensity. Both, before and after surgery, the environmental estimation and self-estimation was very good (77% versus 78%, 78% versus 89%) respectively, and predominant were optimistic attitudes. Post-operative improvement of the quality of life correlating to the clinical state, confirms the suitableness of surgical correction of ASD II, independent of age.