Lesional skin of seborrheic dermatitis patients is characterized by skin barrier dysfunction and correlating alterations in the stratum corneum ceramide composition.

Seborrheic dermatitis (SD) is a chronic inflammatory skin disease characterized by erythematous papulosquamous lesions in sebum rich areas such as the face and scalp. Its pathogenesis appears multifactorial with a disbalanced immune system, Malassezia driven microbial involvement and skin barrier perturbations. Microbial involvement has been well described in SD, but skin barrier involvement remains to be properly elucidated. To determine whether barrier impairment is a critical factor of inflammation in SD alongside microbial dysbiosis, a cross-sectional study was performed in 37 patients with mild-to-moderate facial SD. Their lesional and non-lesional skin was comprehensively and non-invasively assessed with standardized 2D-photography, optical coherence tomography (OCT), microbial profiling including Malassezia species identification, functional skin barrier assessments and ceramide profiling. The presence of inflammation was established through significant increases in erythema, epidermal thickness, vascularization and superficial roughness in lesional skin compared to non-lesional skin. Lesional skin showed a perturbed skin barrier with an underlying skewed ceramide subclass composition, impaired chain elongation and increased chain unsaturation. Changes in ceramide composition correlated with barrier impairment indicating interdependency of the functional barrier and ceramide composition. Lesional skin showed significantly increased Staphylococcus and decreased Cutibacterium abundances but similar Malassezia abundances and mycobial composition compared to non-lesional skin. Principal component analysis highlighted barrier properties as main discriminating features. To conclude, SD is associated with skin barrier dysfunction and changes in the ceramide composition. No significant differences in the abundance of Malassezia were observed. Restoring the cutaneous barrier might be a valid therapeutic approach in the treatment of facial SD.

Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial.

Facial seborrheic dermatitis (SD) is an inflammatory skin disease characterized by erythematous and scaly lesions on the skin with high sebaceous gland activity. The yeast Malassezia is regarded as a key pathogenic driver in this disease, but increased Staphylococcus abundances and barrier dysfunction are implicated as well. Here, we evaluated the antimicrobial peptide omiganan as a treatment for SD since it has shown both antifungal and antibacterial activity. A randomized, patient- and evaluator-blinded trial was performed comparing the four-week, twice daily topical administration of omiganan 1.75%, the comparator ketoconazole 2.00%, and placebo in patients with mild-to-moderate facial SD. Safety was monitored, and efficacy was determined by clinical scoring complemented with imaging. Microbial profiling was performed, and barrier integrity was assessed by trans-epidermal water loss and ceramide lipidomics. Omiganan was safe and well tolerated but did not result in a significant clinical improvement of SD, nor did it affect other biomarkers, compared to the placebo. Ketoconazole significantly reduced the disease severity compared to the placebo, with reduced Malassezia abundances, increased microbial diversity, restored skin barrier function, and decreased short-chain ceramide Cer[NSc34]. No significant decreases in Staphylococcus abundances were observed compared to the placebo. Omiganan is well tolerated but not efficacious in the treatment of facial SD. Previously established antimicrobial and antifungal properties of omiganan could not be demonstrated. Our multimodal characterization of the response to ketoconazole has reaffirmed previous insights into its mechanism of action.

Cardiac age detected by machine learning applied to the surface ECG of healthy subjects: Creation of a benchmark.

OBJECTIVE: The aim of the present study was to develop a neural network to characterize the effect of aging on the ECG in healthy volunteers. Moreover, the impact of the various ECG features on aging was evaluated. METHODS & RESULTS: A total of 6228 healthy subjects without structural heart disease were included in this study. A neural network regression model was created to predict age of the subjects based on their ECG; 577 parameters derived from a 12­lead ECG of each subject were used to develop and validate the neural network; A tenfold cross-validation was performed, using 118 subjects for validation each fold. Using SHapley Additive exPlanations values the impact of the individual features on the prediction of age was determined. Of 6228 subjects tested, 1808 (29%) were females and mean age was 34 years, range 18-75 years. Physiologic age was estimated as a continuous variable with an average error of 6.9 ± 5.6 years (R2 = 0.72 ± 0.04). The correlation was slightly stronger for men (R2 = 0.74) than for women (R2 = 0.66). The most important features on the prediction of physiologic age were T wave morphology indices in leads V4 and V5, and P wave amplitude in leads AVR and II. CONCLUSION: The application of machine learning to the ECG using a neural network regression model, allows accurate estimation of physiologic cardiac age. This technique could be used to pick up subtle age-related cardiac changes, but also estimate the reversing of these age-associated effects by administered treatments.

The association between body temperature and electrocardiographic parameters in normothermic healthy volunteers.

BACKGROUND: Previous studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis' objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers. METHODS: Data from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5-37.5°C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable. RESULTS: Mean age was 33.8 ± 17.5 years and mean body temperature was 36.6 ± 0.4°C. Body temperature was independently associated with age (standardized coefficient [SC] = -0.255, P < .001), female gender (SC = +0.209, P < .001), heart rate (SC = +0.231, P < .001), P-wave axis (SC = -0.051, P < .001), J-point elevation in lead V4 (SC = -0.121, P < .001), and QTcF duration (SC = -0.061, P = .002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = -0.121, P < .001) was independently associated with body temperature. CONCLUSION: Body temperature in normothermic healthy volunteers was associated with heart rate, P-wave axis, J-point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration.

Blood pressure-related electrocardiographic findings in healthy young individuals.

Purpose: Elevated blood pressure induces electrocardiographic changes and is associated with an increase in cardiovascular disease later in life compared to normal blood pressure levels. The purpose of this study was to evaluate the association between normal to high normal blood pressure values (90-139/50-89 mmHg) and electrocardiographic parameters related to cardiac changes in hypertension in healthy young adults.Methods: Data from 1449 volunteers aged 18-30 years collected at our centre were analyzed. Only subjects considered healthy by a physician after review of collected data with systolic blood pressure values between 90 and 139 mmHg and diastolic blood pressure values between 50 and 89 mmHg were included. Subjects were divided into groups with 10 mmHg systolic blood pressure increment between groups for analysis of electrocardiographic differences. Backward multivariate regression analysis with systolic and diastolic blood pressure as a continuous variable was performed.Results: The mean age was 22.7 ± 3.0 years, 73.7% were male. P-wave area, ventricular activation time, QRS-duration, Sokolow-Lyon voltages, Cornell Product, J-point-T-peak duration corrected for heart rate and maximum T-wave duration were significantly different between systolic blood pressure groups. In the multivariate model with gender, body mass index and cholesterol, ventricular rate (standardized coefficient (SC): +0.182, p < .001), ventricular activation time in lead V6 (SC= +0.065, p = .048), Sokolow-Lyon voltage (SC= +0.135, p < .001), and Cornell product (SC= +0.137, p < .001) were independently associated with systolic blood pressure, while ventricular rate (SC= +0.179, p < .001), P-wave area in lead V1 (SC= +0.079, p = .020), and Cornell product (SC= +0.091, p = .006) were independently associated with diastolic blood pressure.Conclusion: Blood pressure-related electrocardiographic changes were observed incrementally in a healthy young population with blood pressure in the normal range. These changes were an increased ventricular rate, increased atrial surface area, ventricular activation time and increased ventricular hypertrophy indices on a standard 12 lead electrocardiogram.