Langerhans cells: Central players in the pathophysiology of atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. AD is a highly complex disease with different subtypes. Many elements of AD pathophysiology have been described, but if/how they interact with each other or which mechanisms are important in which patients is still unclear. Langerhans cells (LCs) are antigen-presenting cells (APCs) in the epidermis. Depending on the context, they can act either pro- or anti-inflammatory. Many different studies have investigated LCs in the context of AD and found them to be connected to all major mechanisms of AD pathophysiology. As APCs, LCs recruit other immune cells and shape the immune response, especially adaptive immunity via polarization of T cells. As sentinel cells, LCs are primary sensors of the skin microbiome and are important for the decision of immunity versus tolerance. LCs are also involved with the integrity of the skin barrier by influencing tight junctions. Finally, LCs are important cells in the neuro-immune crosstalk in the skin. In this review, we provide an overview about the many different roles of LCs in AD. Understanding LCs might bring us closer to a more complete understanding of this highly complex disease. Potentially, modulating LCs might offer new options for targeted therapies for AD patients.

Contemporary Management and Prognostic Factors of Arrhythmia Recurrence in Patients with High-Energy Discharge of Cardiac Implantable Electronic Devices.

Background and Objectives: Understanding the underlying causes of implantable cardioverter-defibrillator (ICD) discharges is vital for effective management. This study aimed to evaluate the characteristics of patients admitted following ICD discharge, focusing on myocardial ischemia as a potential exacerbating factor and potential risk factors for VT recurrence. Materials and Methods: This retrospective, single-center study included 81 patients with high energy discharge from cardiac implantable electronic device admitted urgently to the cardiology department from 2015 to 2022. The exclusion criterion was ST-segment elevation acute coronary syndrome. Data were collected anonymously from electronic medical records. Patients were categorized based on coronary angiography, percutaneous angioplasty, presence of significant stenosis, recurrent ventricular tachycardia (VT), and catheter ablation. Clinical variables, including demographic data, echocardiographic parameters, and pharmacotherapy, were analyzed. The primary endpoint was the recurrence of VT during in-hospital stay. Results: Among 81 patients, predominantly male (86.4%), with a mean age of 63.6 years, 55 (67.9%) had coronary artery disease (CAD) as the primary etiology for ICD implantation. Coronary angiography was performed in 34 patients (42.0%) and showed significant stenosis (>50%) in 18 (41.8%) patients, while 8 (26.0%) individuals underwent percutaneous coronary intervention (PCI). Recurrent VT occurred in 21 subjects (26.3%), while ventricular catheter ablation was performed in 36 patients (44.0%). Referral for urgent coronary angiography was associated with presence of diabetes (p = 0.028) and hyperlipidemia (p = 0.022). Logistic regression analysis confirmed NYHA symptomatic class (OR 4.63, p = 0.04) and LVH (OR 10.59, p = 0.049) were independently associated with relapse of VT. CAD patients underwent catheter ablation more frequently (p = 0.001) than those with dilated cardiomyopathy. Conclusions: The study showed a low referral rate for coronary angiography among patients with ICD discharge. Presence of LVH and preexisting symptomatic class influence arrhythmia recurrence. Understanding these associations can guide personalized management strategies for ICD recipients.

Functional Mitral Regurgitation in Patients with Preserved Ejection Fraction Qualified for Pulmonary Vein Isolation: A Negative Prognostic Factor for Catheter Ablation Efficacy.

Background and Objectives: Functional mitral regurgitation (F-MR) observed in patients with atrial fibrillation could affect the effectiveness of the sinus rhythm restoring procedures. The aim of the study was to evaluate the impact of F-MR on pulmonary vein isolation (PVI) efficacy in patient with preserved ejection fraction (EF). Materials and Methods: One hundred and thirty-six patients with EF ≥ 50% (65.4% males; mean age 56 ± 11 years) with symptomatic paroxysmal or persistent AF qualified for PVI were enrolled into the study. F-MR assessment was performed in transthoracic (TTE) and transesophageal (TEE) echocardiography before the PVI procedure. PVI efficacy was evaluated in three-month and long-term follow-up. Results: F-MR was diagnosed in 74.3% patient in transthoracic echocardiography (TTE) (trace: 26.5%, mild: 43.4%, moderate: 3.7%, severe 0.7%) and 94.9% in transesophageal echocardiography (TEE) (trace: 17.6%, mild: 59.6%, moderate: 16.2%, severe: 1.5%). The PVI three-month efficacy was 75.7% in the three-month and 64% in the long-term observation. Severe F-MR in TEE at baseline was associated with lower three-month PVI efficacy (p = 0.012), while moderate to severe F-MR in TEE was related to inefficient PVI assessed in long-term follow-up (p = 0.041). Conclusions: Significant F-MR confirmed by TEE predicts three-month as well as long-term PVI efficacy.

Left atrial function in obese and non-obese patients undergoing percutaneous pulmonary vein isolation.

Obesity constitutes a risk factor for atrial fibrillation (AF) and modifies the efficacy of invasive AF treatment. Left atrial (LA) global longitudinal strain (GLS), which is measured using speckle-tracking echocardiography (STE), is one of the new methods that are helpful in evaluating the function of LA. The aim of the study was to evaluate LA function in obese and non-obese patients that were undergoing percutaneous pulmonary vein isolation (PVI) before and 6 months after the procedure. 89 patients (F/M: 31/58; mean age: 55.8 ± 9.8 years) with paroxysmal or persistent symptomatic AF that had been qualified for percutaneous PVI were prospectively enrolled in the study. Body mass index (BMI) constituted as a discriminating factor for the study groups: obese group: BMI ≥ 30 kg/m2 (29 patients, F/M: 13/16, mean age: 55.13 ± 10.1 years) and non-obese group BMI < 30 kg/m2 (60 patients, F/M: 18/42, mean age: 57.17 ± 9.0 years). Transthoracic echocardiography (TTE) with LA GLS and segmental longitudinal strain were analysed 1 day before and 6 months after PVI. PVI efficacy was evaluated 6 months after PVI via a seven-day Holter monitoring. Baseline analysis revealed significantly lower two-chamber (2-Ch) LA GLS in the obese patients compared to the non-obese subjects (- 10.55 ± 3.7 vs - 13.11 ± 5.1, p = 0.004). Segmental strain analysis showed no significant differences between the groups. The data that was obtained 6 months after PVI showed a significantly lower 4-Ch LA GLS in the obese patients compared to the non-obese subjects (- 11.04 ± 5.0 vs - 13.91 ± 4.2, p = 0.02), which was accompanied by a significantly lower segmental 4-Ch LA function in the obese patients (med-sept: - 11.66 ± 11.2 vs - 15.97 ± 5.3, p = 0.04; api-sept: - 9.04 ± 6.3 vs - 13.62 ± 6.5, p < 0.001; api-lat: - 7.62 ± 4.0 vs - 13.62 ± 6.5, p < 0.001; med-lat: -9.31 + - 7.9 vs - 15.04 + - 6.3, p = 0.003, global: - 11.04 + - 5.0 vs - 13.91 + - 4.2, p = 0.02). PVI efficacy was confirmed in 52 (58.4%) patients and was similar in both groups. Comparison of the baseline and 6-month strain revealed no differences in LA GLS in either group. Differences in LA GLS before and after the procedure (delta LA GLS) were not obesity dependent. Apical-septal and apical-lateral strain in the obese group, which were measured in 4-Ch view, were significantly lower after the procedure compared to the baseline (p < 0.001). Obese patients with paroxysmal AF were characterised by impaired LA GLS, which is persistent and was accompanied by segmental dysfunction after PVI at the 6-month follow-up. PVI efficacy was comparable between the obese and non-obese patients.

Functional tricuspid regurgitation and efficacy of electrical cardioversion in patients with atrial fibrillation and atrial functional mitral regurgitation.

INTRODUCTION: Atrial functional mitral regurgitation (afMR) is common in patients with atrial fibrillation (AF). The presence of functional tricuspid regurgitation (fTR), which arises as a secondary effect of afMR, has the potential to impact the effectiveness of procedures aimed at restoring normal heart rhythm. In this study, we sought to evaluate the efficacy of electrical cardioversion (CVE) in AF regarding the presence and degree of fTR in patients with afMR. MATERIAL AND METHODS: Retrospective analysis included 521 patients with persistent AF on optimal medical therapy undergoing CVE. 157 (30.1%) patients had afMR (characterized by left ventricle ejection fraction ≥ 50% and LA dilatation) and were divided into 2 groups: the group with fTR (107, 68.2%) and the group without fTR (50, 31.9%). RESULTS: Patients with afMR and fTR had a higher prevalence of metabolic syndrome (p = 0.02) and greater right atrial area (p < 0.01) compared to patients without fTR. The efficacy of CVE was lower in the group with fTR in comparison to patients with isolated afMR (82.2% vs. 94%; p = 0.048) and it was unrelated to the degree of fTR (p = 0.15) and RVSP (p = 0.56). The energy required for successful CVE was comparable regardless of the presence (p = 0.26) or severity of fTR (p = 0.94). CONCLUSIONS: The fTR frequently coexists with afMR and it significantly diminishes the effectiveness of CVE for treating AF. The degree of fTR does not appear to influence the efficacy of CVE.

Epidermal/Dermal Separation Techniques and Analysis of Cell Populations in Human Skin Sheets.

Human skin consists of three compartments, each endowed with a particular structure and the presence of several immune and nonimmune cells that together comprise a protective shield and orchestrate multiple processes in the skin. Appropriate processing of human skin samples acquired from healthy volunteers or patients is essential for successful analysis in basic, translational, and clinical research to obtain accurate and reliable results, despite differences between individuals. From the wide range of available assays and methods, it is necessary to select the suitable method for separation of skin compartments, which will provide preservation or high viability of skin cells or whole structures that will be analyzed or further processed. In this paper, we review and discuss skin separation methods and compare their features such as processing time, cell viability, location of the basement membrane after detachment of the epidermis from the dermis, and their application. Furthermore, we visualize different cell populations and structures in epidermal and dermal sheets using confocal microscopy. It is aimed to provide an overview of the optimal processing of human skin samples and their possible application.

Repeated Dose of Contrast Media and the Risk of Contrast-Induced Acute Kidney Injury in a Broad Population of Patients Hospitalized in Cardiology Department.

Contrast-induced acute kidney injury (CI-AKI) can lead to the development of chronic kidney disease (CKD) and impaired in-hospital and long-term outcomes among cardiac patients. The aim of this study was to evaluate the impact of repeated contrast media (CM) administration during a single hospitalization on the rate of CI-AKI. The study group (n = 138) comprised patients with different diagnoses who received CM more than once during hospitalization, while the control group (n = 153) involved CAD patients subject to a single CM dose. Following propensity score matching (PSM), both groups of n = 84 were evenly matched in terms of major baseline variables. CI-AKI was defined by an absolute increase in SCr ≥ 0.3 mg/dL or >50% relative to the baseline value within 48-72 h from the last CM dose. Patients in the study group were older, had a higher prevalence of diabetes and CKD, received a higher total volume of CM, had a lower left ventricular ejection fraction, lower prevalence of multivessel coronary artery disease (MV-CAD), and a trend towards a lower prevalence of arterial hypertension and smoking. SCr did not differ between the study and control groups at 72 h after the CM use. CI-AKI occurred in 18 patients in the study (13.0%) and in 18 patients (11.8%) in the control group (p = 0.741). The rate of CI-AKI was also comparable following the PSM (13.1% vs. 13.1%, p = 1.0). Logistic regression analysis revealed that CKD, diabetes mellitus, MV-CAD, age, and non-steroidal anti-inflammatory drugs use, but not repeated CM use, were independent predictors of CI-AKI.

Clinical Characteristics of Atrial Flutter and Its Response to Pharmacological Cardioversion with Amiodarone in Comparison to Atrial Fibrillation.

BACKGROUND: Unlike atrial fibrillation (AF), atrial flutter (AFl) is thought to be relatively refractory to pharmacological cardioversion (PC), but the evidence is scarce. The aim of this study was to evaluate the clinical characteristics and efficacy of the PC of AFl with amiodarone in comparison to AF. MATERIALS AND METHODS: This retrospective study covered 727 patients with urgent consult for AF/AFl in a high-volume emergency department between 2015 and 2018. AFl was diagnosed in 222 (30.5%; median age: 68 (62; 75) years; 65.3% men). In a nested case-control study, 59 control patients with AF, matched in terms of age and sex with 60 AFl patients, were subject to PC with amiodarone. The primary endpoint was return of sinus rhythm confirmed using a 12-lead ECG. RESULTS: The AFl population had a median CHA2DS2-VASc score of 3 (2; 4) and episode duration of 72 h (16; 120). In the AFl cohort, 36% of patients were initially subject to PC, 33.3% to electrical cardioversion (EC) and 40.5% to catheter ablation. In comparison to the AF group, the AFl patients required a longer hospitalization time, had a higher rate of EC (p < 0.001) and less frequent use of PC (p < 0.001) and, lower left ventricular ejection fraction (p < 0.001) and more pronounced cardiovascular risk factors. The efficacy of PC with amiodarone was significantly lower in AFl than AF group (39% vs. 65%, relative risk (RR) 0.60, p = 0.007). CONCLUSIONS: AFl patients shared a greater burden of comorbidities than AF patients, while the efficacy of PC in AFl was low. Patients should be initially managed with primary electrical cardioversion.

Positive left atrial remodeling in patients with paroxysmal atrial fibrillation after a successful radiofrequency pulmonary vein isolation.

BACKGROUND: A potential relationship between the initial left atrial (LA) echocardiographic parameters and LA remodeling after pulmonary vein isolation using (PVI) radiofrequency energy energy with effectiveness of this treatment was discussed. AIM: We aimed to determine the relationship between initial and post-follow-up transthoracic echocardiography- derived predictors of successful PVI in patients with paroxysmal atrial fibrillation (AF). METHODS: Eighty patients with paroxysmal AF (aged 58 [interquartile range, IQR, 50-63] years; male, 50 [62.5%]), hospitalized for the first PVI procedure were included. Before and after a minimum of 6 months of follow-up, clinical and echocardiographic evaluations were performed. LA morphological parameters (diameter, volumes, and other detailed LA parameters), as well as LA peak segmental and global longitudinal strains (PLS) and LA wall strain synchrony were assessed. RESULTS: In the whole group after the follow-up period, patients presented higher mean LA Volconduit. Patients with no AF recurrences had lower post-PVI LA volumes, higher LA ejection fraction, and LA expansion index when compared to the patients after ineffective PVI. Patients who maintained sinus rhythm after the PVI procedure were characterized by higher initial segmental strains: LA PLSbasal-inferior and PLSapical-septal, as well as higher LA wall strain dispersion over time. CONCLUSIONS: Some echocardiographic parameters related to LA morphology improve after successful PVI treatment. LA strains and wall strain dispersion over time are not related to LA remodeling after a successful PVI procedure. However, the baseline LA standard and novel echocardiographic parameters cannot be used for remote evaluation of the effectiveness of the PVI procedure.

Clinical characteristics and risk factors of in-hospital mortality among patients undergoing percutaneous pericardiocentesis.

Background: Percutaneous pericardiocentesis represents a salvage procedure in case of cardiac tamponade and diagnostic procedure in chronic pericardial effusion of unknown source. The study aimed to analyze the clinical characteristics of patients subject to pericardiocentesis and the predictors of in-hospital mortality. Methods: The study represents a registry that covered consecutive patients undergoing percutaneous pericardiocentesis from 2011 to 2022 in high-volume tertiary reference center. Electronic health records were queried to obtain demographic and clinical variables. The primary endpoint was in-hospital mortality, while secondary endpoint was the need for recurrent pericardiocentesis. Results: Out of 132 456 patients hospitalized in the prespecified period, 247 patients were subject to percutaneous pericardiocentesis (53.9% women; median age of 66 years) who underwent 273 procedures. In-hospital death was reported in 14 patients (5.67%), while recurrent pericardiocentesis in 24 patients (9.72%). Iatrogenic cause was the most common etiology (42.5%), followed by neoplastic disease (23.1%) and idiopathic effusion (14.57%). In logistic regression analysis in-hospital mortality was associated with myocardial infarction (MI)-related etiology (p = 0.001) and recurrent/persistent cardiogenic shock (p = 0.001). Conclusions: Iatrogenic etiology and neoplastic disease seem to be the most common indications for pericardiocentesis, while in-hospital mortality was particularly high in patients with spontaneous tamponade in the course of MI.

Interoperability of RTN1A in dendrite dynamics and immune functions in human Langerhans cells.

Skin is an active immune organ where professional antigen-presenting cells such as epidermal Langerhans cells (LCs) link innate and adaptive immune responses. While Reticulon 1A (RTN1A) was recently identified in LCs and dendritic cells in cutaneous and lymphoid tissues of humans and mice, its function is still unclear. Here, we studied the involvement of this protein in cytoskeletal remodeling and immune responses toward pathogens by stimulation of Toll-like receptors (TLRs) in resident LCs (rLCs) and emigrated LCs (eLCs) in human epidermis ex vivo and in a transgenic THP-1 RTN1A+ cell line. Hampering RTN1A functionality through an inhibitory antibody induced significant dendrite retraction of rLCs and inhibited their emigration. Similarly, expression of RTN1A in THP-1 cells significantly altered their morphology, enhanced aggregation potential, and inhibited the Ca2+ flux. Differentiated THP-1 RTN1A+ macrophages exhibited long cell protrusions and a larger cell body size in comparison to wild-type cells. Further, stimulation of epidermal sheets with bacterial lipoproteins (TLR1/2 and TLR2 agonists) and single-stranded RNA (TLR7 agonist) resulted in the formation of substantial clusters of rLCs and a significant decrease of RTN1A expression in eLCs. Together, our data indicate involvement of RTN1A in dendrite dynamics and structural plasticity of primary LCs. Moreover, we discovered a relation between activation of TLRs, clustering of LCs, and downregulation of RTN1A within the epidermis, thus indicating an important role of RTN1A in LC residency and maintaining tissue homeostasis.

Efficacy of Electrical Cardioversion in Relation to Occurrence and Type of Functional Mitral Regurgitation in Patients with Atrial Fibrillation.

Background: Recent studies have changed the perception of rhythm control in the treatment of atrial fibrillation (AF). Functional mitral regurgitation (fMR) can be both a cause and a consequence of AF and may influence rhythm restoration procedures. Materials and methods: A retrospective analysis included 182 consecutive patients with AF on optimal medical therapy (OMT) undergoing electrical cardioversion (CVE). Based on transthoracic echocardiography, the study group was divided into 20 (11%) patients without mitral regurgitation (MR) and 132 (82%) with fMR 77 (58%) with atrial fMR (afMR; left ventricle ejection fraction (LVEF) ≥ 50%, left atrial (LA) dilatation) and 55 (42%) and with ventricular fMR (vfMR; LVEF < 50%). Patients with severe and organic MR were excluded from the study. Results: vfMR patients had a greater incidence of kidney failure (p = 0.01) and coronary heart disease (p = 0.02); more frequent use of diuretics during hospitalization (p < 0.01); greater LA diameter and area (p < 0.01; p < 0.01) than afMR patients. CVE efficiency was high in all four groups (84−95%). The presence and type of fMR did not affect the efficacy of CVE (p = 0.2; p = 0.9) and did not require the use of more energy (p = 0.4; p = 0.8). The independent predictor of successful CVE was the amount of white blood cells (OR 0.74, p < 0.05). Conclusions: Efficacy of CVE is high among AF patients on OMT regardless of the incidence and type of fMR. Subclinical inflammation should be excluded before elective CVE because it may decrease its efficacy.

Heart failure and the risk of left atrial thrombus formation in patients with atrial fibrillation or atrial flutter.

AIMS: The aim of the study was to evaluate the prevalence of left atrial thrombus (LAT) on transoesophageal echocardiography (TOE) in patients with atrial fibrillation or atrial flutter (AF/AFl) with reference to the presence of heart failure (HF) and its subtypes. METHODS AND RESULTS: The research is a sub-study of the multicentre, prospective, observational Left Atrial Thrombus on Transoesophageal Echocardiography (LATTEE) registry, which comprised 3109 consecutive patients with AF/AFl undergoing TOE prior to direct current cardioversion or catheter ablation. TOE parameters, including presence of LAT, were compared between patients with and without HF and across different subtypes of HF, including HF with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF). HF was diagnosed in 1336 patients (43%). HF patients had higher prevalence of LAT than non-HF patients (12.8% vs. 4.4%; P < 0.001). LAT presence increased with more advanced type of systolic dysfunction (HFpEF vs. HFmrEF vs. HFrEF: 7.4% vs. 10.5% vs. 20.3%; P < 0.001). Univariate analysis revealed that HFrEF (odds ratio [OR] 4.13; 95% confidence interval [95% CI]: 3.13-5.46), but not HFmrEF or HFpEF, was associated with the presence of LAT. Multivariable logistic regression indicated that lower left ventricular ejection fraction (OR per 1%: 0.94; 95% CI 0.93-0.95) was an independent predictor of LAT formation. Receiver operator characteristic analysis showed LVEF ≤48% adequately predicted increased risk of LAT presence (area under the curve [AUC] 0.74; P < 0.0001). CONCLUSION: The diagnosis of HFrEF, but neither HFmrEF nor HFpEF, confers a considerable risk of LAT presence despite widespread utilization of adequate anticoagulation.

Biomarkers of left atrial overload in obese and nonobese patients with atrial fibrillation qualified for electrical cardioversion.

BACKGROUND: Biomarkers of left atrial (LA) overload are considered factors affecting the efficacy of atrial fibrillation (AF) treatment. Increasing obesity rates contribute to a growing number of obese patients qualified for electrical cardioversion (CVE).Biomarkers of left atrial (LA) overload are considered as factors influencing efficacy of atrial fibrillation (AF) treatment. The increasing rate of obesity contributes to obese patients constituting a significant group of subjects qualified to electrical cardioversion (CVE). AIMS: The aim of the study was to evaluate serum concentrations of biomarkers of LA overload and their impact on the efficacy of CVE. METHODS: A total of 82 patients with persistent AF who underwent successful CVE were prospectively enrolled in the study. The study population was divided into the obese group (OG) and the nonobese group (NOG). The serum levels of the following biomarkers were measured on the day of admission and at follow­up: high­sensitivity C­reactive protein (hs­CRP), N­terminal pro­B­type natriuretic peptide, copeptin, galectin 3, growth differentiation factor 15 (GDF­15), and renalase. RESULTS: Baseline and follow­up hs­CRP levels were increased in the OG compared with the NOG. Four­week CVE efficacy was 38.8% in the OG and 60.6% in the NOG. Time of the observation, allocation to the groups, and CVE outcomes showed no associations with most LA biomarkers during follow­up. Baseline concentrations of 2 biomarkers of LA overload were associated with clinical characteristics of the study group, that is, log10 serum GDF­15 and log10 serum renalase levels correlated positively with the CHA2DS2­VASc score. CONCLUSIONS: Although obesity modifies the long­term efficacy of CVE, the OG and NOG did not differ significantly in most biomarkers of LA overload, except hs­CRP. The efficacy of CVE seems to be independent of the levels of biomarkers. A favorable procedure outcome did not affect their blood concentrations.

Distinct Distribution of RTN1A in Immune Cells in Mouse Skin and Lymphoid Organs.

The endoplasmic reticulum-associated protein reticulon 1A (RTN1A) is primarily expressed in neuronal tissues but was recently identified also specifically in cells of the dendritic cell (DC) lineage, including epidermal Langerhans cells (LCs) and dermal DCs in human skin. In this study, we found that in mice major histocompatibility complex class II (MHCII)+CD207+ LCs but not dermal DCs express RTN1A. Further, RTN1A expression was identified in CD45+MHCII+CD207+ cells of the lymph node and spleen but not in the thymus. Of note, RTN1A was expressed in CD207 low LCs in adult skin as well as emigrated LCs and DCs in lymph nodes and marginally in CD207 hi cells. Ontogeny studies revealed that RTN1A expression occurred before the appearance of the LC markers MHCII and CD207 in LC precursors, while dermal DC and T cell precursors remained negative during skin development. Analogous to the expression of RTN1A in neural tissue, we identified expression of RTN1A in skin nerves. Immunostaining revealed co-localization of RTN1A with nerve neurofilaments only in fetal but not in newborn or adult dermis. Our findings suggest that RTN1A might be involved in the LC differentiation process given its early expression in LC precursors and stable expression onward. Further analysis of the RTN1A expression pattern will enable the elucidation of the functional roles of RTN1A in both the immune and the nervous system of the skin.

Effects of lecithin-based nanoemulsions on skin: Short-time cytotoxicity MTT and BrdU studies, skin penetration of surfactants and additives and the delivery of curcumin.

Surfactants are important ingredients in pharmaceutical and cosmetic formulations, as in creams, shampoos or shower gels. As conventional emulsifiers such as sodium dodecyl sulfate (SDS) have fallen into disrepute due to their skin irritation potential, the naturally occurring lecithins are being investigated as a potential alternative. Thus, lecithin-based nanoemulsions with and without the drug curcumin, known for its wound healing properties, were produced and characterised in terms of their particle size, polydispersity index (PDI) and zeta potential and compared to SDS-based formulations. In vitro toxicity of the produced blank nanoemulsions was assessed with primary human keratinocytes and fibroblasts using two different cell viability assays (BrdU and EZ4U). Further, we investigated the penetration profiles of the deployed surfactants and oil components using combined ATR-FTIR/tape stripping experiments and confirmed the ability of the lecithin-based nanoemulsions to deliver curcumin into the stratum corneum in tape stripping-UV/Vis experiments. All manufactured nanoemulsions showed droplet sizes under 250 nm with satisfying PDI and zeta potential values. Viability assays with human skin cells clearly indicated that lecithin-based nanoemulsions were superior to SDS-based formulations. ATR-FTIR tests showed that lecithin and oil components remained in the superficial layers of the stratum corneum, suggesting a low risk for skin irritation. Ex vivo tape stripping experiments revealed that the kind of oil used in the nanoemulsion seemed to influence the depth of curcumin penetration into the stratum corneum.

Renalase is associated with adverse left atrial remodelling and disease burden in patients with atrial fibrillation undergoing pulmonary vein isolation.

BACKGROUND: Renalase is a catecholamine-metabolising enzyme, but its possible association with atrial fibrillation (AF) remains unknown. AIM: We sought to evaluate plasma renalase concentration in patients with AF undergoing pulmonary vein isolation (PVI) with respect to AF clinical characteristics, left atrial (LA) remodelling, and PVI efficacy. METHODS: This case-control study included 69 patients (median age 58 years) with either paroxysmal (89%) or persistent (11%) AF, referred for PVI, and a control group consisting of 15 patients without AF, matched for age, sex, and comorbidi-ties. An evaluation of transthoracic echocardiography with LA speckle tracking and plasma renalase concentration using an enzyme-linked immunosorbent assay was performed. AF recurrence was defined as any AF episode on seven-day electro-cardiographic monitoring at six-month follow-up. RESULTS: Renalase level was higher in the study group than in the control group (mean 27.99 vs. 21.48 µg/mL, p = 0.004), but it was lower in patients with persistent AF (19.05 vs. 28.77 µg/mL; p = 0.023) and among patients with AF episodes di-rectly preceding PVI (24.50 vs. 29.66 µg/mL; p = 0.04). Renalase concentration within the first quartile was associated with higher mean heart rate (70 vs. 61 bpm, p = 0.029), greater AF burden (36.9% vs. 9.3%, p = 0.027), greater LA diameter (41.1 vs. 37.9 mm, p = 0.011), and a trend towards less negative global LA strain (-9.4 vs. -13.5, p = 0.082). Logistic regres-sion revealed that global four-chamber LA strain was the only independent predictor of renalase variability (p = 0.0045). Renalase concentration did not predict AF recurrence at six-month follow-up (area under curve [AUC] = 0.614, p = 0.216). CONCLUSIONS: Low renalase level may be associated with impaired rate control, higher AF burden, and advanced LA remodel-ling in AF patients undergoing PVI, but it does not predict sinus rhythm maintenance.