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.

Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo.

The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands, including biomaterials in vitro, and low ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3-mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, ficolin-1 and -3. In the Bioline® group the ficolin-2 levels decreased significantly after initiation of surgery (P < 0.0001) and remained reduced throughout the sampling period. This was not seen for Phisio®-coated circuits. Ficolin-3-mediated complement activation potential was reduced significantly in both groups after start of operation (P < 0.0001), whereas soluble C3a and TCC in the samples were increased (P < 0.0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures.

Complement activation and its prognostic role in post-cardiac arrest patients.

Cardiac arrest causes generalized ischaemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34 °C body temperature for 24 h and then allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and 24 h, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9 and Bb) were measured by ELISA in blood samples. Patients were followed up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 h after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose post-cardiac arrest patients.

Interobserver agreement and accuracy of bedside estimation of right and left ventricular ejection fraction in acute myocardial infarction.

Ninety-eight patients with acute myocardial infarction were examined by 3 clinicians who, independently of each other, gave an estimate of left ventricular (LV) and right ventricular (RV) ejection fraction (EF) in each patient. Their estimates were based on physical examination, chest x-ray, electrocardiogram, patient history and clinical course during admission. Ejection fractions were estimated as belonging to 1 of 4 categories: normal (LVEF greater than or equal to 0.53, RVEF greater than or equal to 0.57), mildly reduced (LVEF 0.40 to 0.52, RVEF 0.45 to 0.56), moderately reduced (LVEF 0.30 to 0.39, RVEF 0.35 to 0.44) or severely reduced (LVEF less than 0.30, RVEF less than 0.35). Radionuclide ventriculography was carried out immediately after the physical examination. LVEF was correctly estimated in 43% of all examinations, deviated from radionuclide LVEF by 1 LVEF category in 45% and by 2 LVEF categories in 12%. The 3 clinicians agreed on estimated LVEF in only 32% of the patients. RVEF was correctly estimated in 67% of the examinations, but none of the clinicians identified greater than 43% of the relatively few patients with reduced radionuclide RVEF and they greatly disagreed as to who among the patients had a reduced RVEF. Previous myocardial infarction, electrocardiographic infarct location, Killip class, physical signs of left- and right-sided heart failure, radiographic pulmonary congestion and cardiomegaly were analyzed to determine which were the most helpful in predicting LVEF and RVEF. The results disclosed that several variables, traditionally believed to be reliable indexes of reduced ventricular function, were surprisingly poor predictors of LVEF and RVEF.

Evaluation of intravenous radionuclide angiography in detection of occlusive disease of the iliac arteries.

Radionuclide angiography (angioscintigraphy) of the iliac arteries was performed in 173 patients consecutively referred for arterial insufficiency of the legs. In 83 of the patients femoral angiography was also performed. The interobserver variation was evaluated by the agreement indices, kappa (K) and weighted kappa (Kw). For angiography the interobserver agreement was high (K and Kw 0.65 and 0.77 respectively). For angioscintigraphy the agreement between observers was fair (K = 0.52, Kw = 0.68), and equal to the intraobserver agreement (K = 0.55, Kw = 0.65). The comparison between angioscintigraphy and angiography gave K-values of 0.22-0.31 and Kw-values of 0.37-0.48. The nosographic sensitivity of angioscintigraphy was 61%, the nosographic specificity was 93%, and the predictive value for both a positive and a negative test was 83%. The prevalence of occlusion or severe stenosis was 34%. Inguinal pulse palpation detected 48% of iliac occlusions. It is concluded that the reliability of angioscintigraphy in the diagnosis of iliac arterial occlusive disease is acceptable for a non-invasive, rapid, inexpensive and widely available screening procedure. Although anatomical details are not visualized the information obtained is useful for the detailed planning and choice of subsequent diagnostic and therapeutic procedures. The method is well suited for repeat studies and may be modified to include the femoral arteries.

Bounded-depth threshold circuits for computer-assisted CT image classification.

We present a stochastic algorithm that computes threshold circuits designed to discriminate between two classes of computed tomography (CT) images. The algorithm employs a partition of training examples into several classes according to the average grey scale value of images. For each class, a sub-circuit is computed, where the first layer of the sub-circuit is calculated by a new combination of the Perceptron algorithm with a special type of simulated annealing. The algorithm is evaluated for the case of liver tissue classification. A depth-five threshold circuit (with pre-processing: depth-seven) is calculated from 400 positive (abnormal findings) and 400 negative (normal liver tissue) examples. The examples are of size n=14,161 (119 x 119) with an 8 bit grey scale. On test sets of 100 positive and 100 negative examples (all different from the learning set) we obtain a correct classification close to 99%. The total sequential run-time to compute a depth-five circuit is about 75h up to 230h on a SUN Ultra 5/360 workstation, depending on the width of the threshold circuit at depth-three. In our computational experiments, the depth-five circuits were calculated from three simultaneous runs for depth-four circuits. The classification of a single image is performed within a few seconds.

Allergic disease in children. Guide to diagnosis and treatment.

Allergy is responsible for many problems in the pediatric age-group. At times the most difficult job for the physician is to determine if the patient is indeed allergic and, if so, to what. Allergy skin testing remains the first choice for diagnostic study. Treatment consists of avoiding the offending allergen if possible, controlling symptoms with appropriate medication, and using immunotherapy if indicated.

[Attitudes of Danish physicians to consumer charges in the health care system]. / Danske laegers holdning til brugerbetaling i sundhedssektoren.

Consumer charges in connection with visits to a doctor are common in a number of countries often used for comparison but are not employed in Denmark. The Danish Medical Association is opposed to consumer charges in health care and a test sample out of 1,000 of the Medical Association chosen at random showed a definite majority opposed to consumer charges. A minority of the profession was in favour of a nominal fee of less than 70 Danish crowns (approximately 7 pounds) for visits to a doctor while scarcely 4% considered that the fee should be more than 100 Danish crowns (approximately 10 pounds). 40% of the participants considered that the consumer charge would have to exceed 100 Danish crowns before it was of any consequences for the health of the patient. In addition, this study revealed that female doctors were more opposed to consumer charges than their male colleagues. At present, more women than men commence the medical curriculum in Denmark and it must therefore be anticipated that the percentage of women in the Danish Medical Association will soon exceed the present 30%. The resistance os the Danish Medical Association to consumer charges in health care will, therefore, probably be retained.

[Attitude of Danish physicians to the health care services]. / Danske laegers holdning til service i sundhedssektoren.

In recent years, Danish society has focused on the service and the information available for patients in health care. A test sample out of 1,000 members of the Danish Medical Association selected at random revealed that the majority had positive attitudes to service and information in health care. The study also indicated that doctors do not consider that any particular dress code is particularly appropriate but consider that personal appearance and the way patients are addressed are individual matters. This individualistic attitude which is consistent with Mintzberg's sociological structural theory does not invariably seem appropriate.

Consumer and farmer safety evaluation of application of botanical pesticides in black pepper crop protection.

This study presents a consumer and farmer safety evaluation on the use of four botanical pesticides in pepper berry crop protection. The pesticides evaluated include preparations from clove, tuba root, sweet flag and pyrethrum. Their safety evaluation was based on their active ingredients being eugenol, rotenone, ß-asarone and pyrethrins, respectively. Botanical pesticides from Acorus calamus are of possible concern because of the genotoxic and carcinogenic ingredient ß-asarone although estimated margins of exposure (MOE) for consumers indicate a low priority for risk management. For the other three botanical pesticides the margin of safety (MOS) between established acute reference doses and/or acceptable daily intake values and intake estimates for the consumer, resulting from their use as a botanical pesticide are not of safety concern, with the exception for levels of rotenone upon use of tuba root extracts on stored berries. Used levels of clove and pyrethrum as botanical pesticides in pepper berry crop production is not of safety concern for consumers or farmers, whereas for use of tuba root and sweet flag some risk factors were defined requiring further evaluation and/or risk management. It seems prudent to look for alternatives for use of sweet flag extracts containing ß-asarone.

[Multislice computed tomographic myelography]. / CT-Myelographie in Mehrschichttechnik.

While magnetic resonance imaging (MRI) is the first line modality in depicting intramedullary spinal lesions, computed tomographic (CT) myelography has gained renewed attention due to the introduction of multislice scanning (MS-CT). Compared with conventional CT, MS-CT permits rapid, high-resolution imaging of various spinal pathologies with extended scan length. Although soft tissue contrast is inferior to that with MRI, MS-CT myelography performs best in detailed assessment of osseous pathologies, 3D imaging of orthopedic and anesthesiologic implants, and showing dural leakage and causes of CSF circulation impairment. Whenever MRI is not available or contraindicated, MS-CT myelography is the method of choice for evaluating spinal lesions.