Low stroke incidence in the TEMPiS telestroke network during COVID-19 pandemic: Effect of lockdown on thrombolysis and thrombectomy.

BACKGROUND: During the COVID-19 pandemic emergency departments have noted a significant decrease in stroke patients. We performed a timely analysis of the Bavarian telestroke TEMPiS "working diagnosis" database. METHODS: Twelve hospitals from the TEMPiS network were selected. Data collected for January through April in years 2017 through 2020 were extracted and analyzed for presumed and definite ischemic stroke (IS), amongst other disorders. In addition, recommendations for intravenous thrombolysis (rtPA) and endovascular thrombectomy (EVT) were noted and mobility data of the region analyzed. If statistically valid, group-comparison was tested with Fisher's exact test considering unpaired observations and ap-value < 0.05 was considered significant. RESULTS: Upon lockdown in mid-March 2020, we observed a significant reduction in recommendations for rtPA compared to the preceding three years (14.7% [2017-2019] vs. 9.2% [2020], p = 0.0232). Recommendations for EVT were significantly higher in January to mid-March 2020 compared to 2017-2019 (5.4% [2017-2019] vs. 9.3% [2020], p = 0.0013) reflecting its increasing importance. Following the COVID-19 lockdown mid-March 2020 the number of EVT decreased back to levels in 2017-2019 (7.4% [2017-2019] vs. 7.6% [2020], p = 0.1719). Absolute numbers of IS decreased in parallel to mobility data. CONCLUSIONS: The reduced stroke incidence during the COVID-19 pandemic may in part be explained by patient avoidance to seek emergency stroke care and may have an association to population mobility. Increasing mobility may induce a rebound effect and may conflict with a potential second COVID-19 wave. Telemedical networks may be ideal databases to study such effects in near-real time.

Exercises and Skin Physiology During International Space Station Expeditions.

BACKGROUND: The first skin physiological pilot experiment (SkinA) on a single astronaut showed a deterioration of the skin. In a follow-up experiment (SkinB) we showed that skin physiological parameters improved on average. However, it is well known that sports have positive effects on the skin, that astronauts prefer special sports devices, and do sports with different intensity. The aim of this study was to analyze the different sports activities of SkinB astronauts and to find out whether they have an influence on the skin physiological parameters.METHODS: The cumulative distance covered on the treadmill and on the cycle ergometer as well as the repetition of arm-related exercises have been calculated and possible correlation between sports activities and skin physiological parameters have been analyzed.RESULTS: The average distance covered for all six astronauts per day is 1364 AU on the treadmill T2, and 11,077 AU on the cycle ergometer CEVIS. In addition, the astronauts performed an average of about 73 repetitions of all arm-related exercises daily. Here, we were able to show very well how differently the astronauts on the ISS train. In addition, a decreasing trend in skin volume can be observed in astronauts with increasing activity on the bicycle and more repetitions on arm-related exercises.CONCLUSION: Increased activity on the cycle ergometer and increased arm-related exercises have a medium negative impact on the parameter skin volume and thus reflects more fluid content in the skin. No correlations between sports activities and skin moisture/skin barrier function could be found.Braun N, Hunsdieck B, Theek C, Ickstadt K, Heinrich U. Exercises and skin physiology during International Space Station expeditions. Aerosp Med Hum Perform. 2021; 92(3):160166.

Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study.

AIMS: Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405). METHODS AND RESULTS: Patients had left ventricular ejection fraction between ≥30% and <50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) >125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed a median 23.3% NT-proBNP reduction, vs. a 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and encouraging positive trends for relevant cardiac fibrosis biomarkers. CONCLUSION: This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. Although this study is limited by the small patient numbers, the indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.

The Influence of Short-Wave and Long-Wave Radiation Spectrum on the Photostability of Sunscreens.

BACKGROUND: Sunscreen products aim to help protect the skin against UV radiation and consequently reduce the risk of early skin ageing and skin cancer. However, it is well known that some sunscreen ingredients are not photostable, but this usually refers to irradiation with UV light. Moreover, it has to be mentioned that a relative cumulative erythema effectiveness compliant light source is used for the in vivo sun protection factor (SPF) testing. Here, UV simulators equipped with a xenon arc lamp use filters such as WG320 and UG11 (thickness 1 mm) to minimize infrared (IR) radiation and wavelength below 300 nm. However, under practical conditions, the sunscreen product is not only exposed to UVA/B light, but also to visible light (VIS) and IR light. In fact, the spectrum of solar radiation is composed of approximately 7% UV, 39% VIS and 54% IR. AIMS: To investigate the influence of short-wave and long-wave radiation on the photostability of sunscreens. METHODS: Irradiation was performed with the Suntest CPS+ that is considered to closely imitate solar radiation. The filter UG11 (thickness 1 mm), which absorbs much of the VIS and IR light, and the glass filter WG320 (thickness 2 mm), which effectively absorbs radiation of wavelengths less than 300 nm, were used in the Suntest CPS+ both individually and in combination and were inserted between the light source and the samples. The following transmission measurements were carried out with Labsphere's UV-2000s device. Here, the effectiveness (percentage change of SPF before irradiation to SPF after irradiation) as a measure of the photostability was calculated. RESULTS: As expected after total solar spectrum irradiation, the effectiveness in all tested sunscreens is lower compared to relative cumulative erythema effectiveness light used for in vitro testing of SPF. In the reference sunscreen formula S2 as well as in the two different sunscreen products, especially long-wave radiation (>400 nm) had an effect on photostability, whereas short-wave radiation had only a minor impact. In contrast, in the BASF sun care gel line only short-wave radiation below 300 nm had an effect on photostability, and blocking VIS and IR light had no effect at all. CONCLUSION: Based on these data, we can conclude that short waves and/or VIS + IR light have an influence on the photostability of sunscreens.

Surface Evaluation of Living Skin (SELS) parameter correlation analysis using data taken from astronauts working under extreme conditions of microgravity.

BACKGROUND: In space, due to fluid shift a 45% decrease in the skin topography parameter volume (mm3 ) was seen using the VisioScan® camera. Simultaneously, the parameters roughness, scaling and wrinkles changed dramatically as well. Thus, the present study has the objective to understand the relationship between the SELS parameters under extreme conditions and their application by addressing scientific-dermatological questions. MATERIAL AND METHODS: SELS measurements were performed on the volar forearms of six astronauts. The Pearson correlation coefficient was used to determine the association between the variables. RESULTS: A significant correlation was found between the skin topography parameter volume and the skin parameters roughness, scaling and wrinkles. A closer look at each astronaut revealed a significant correlation for all astronauts for the parameters volume and roughness and for more than 65% of the astronauts for the parameters volume and scaling and volume and wrinkles. However, no correlation could be found between the parameters skin hydration and roughness and scaling, respectively. CONCLUSION: Only the parameter skin volume leads to meaningful data under microgravity. Physiological changes observed by fluid shift are comparable to the skin condition edema on earth. Based on the obtained data, we can conclude that the formulas for the SELS parameters roughness, scaling and wrinkles for this special skin condition need to be reviewed.

Application of an Easy-to-Perform High-Energy and Low-End Visible Light Transmittance Method and the Influence of Tinted Sunscreens on High-Energy/Low-End Visible Light Transmittance and Infrared Protection.

BACKGROUND: About 50% of the sun's radiation arriving on earth is visible light (VIS). For a long time, its effects on human health have not been fully investigated. But recently, the influence of VIS has gained more attention, especially regarding skin physiology. Studies showed various effects, many of them harmful, comparable to UV radiation. As a result, there are now a few sunscreens commercially available which claim protection against VIS. The question of whether protection is necessary is still much discussed. AIMS: The objective of this study was to develop an easy-to-perform high-energy visible (HEV) and low-end visible (LEV) light transmittance method to determine the direct VIS protection of sunscreens and other cosmetic samples. Furthermore, the influence of the brightness of the tested products on the HEV, LEV, and infrared A protection was investigated. METHODS: An experimental setup consisting of a light source, a VIS-transmissible filter system, and a sensor unit was built to measure the direct VIS protection of sunscreens and other daily skin care products in two ranges of the VIS area. For a closer look, the brightness of the samples was evaluated by photometric assessment. RESULTS/CONCLUSION: The experimental setup could be validated. It could be demonstrated for the first time that there is a strong positive linear correlation between transmittance and brightness of tinted sunscreen and daily skin care products with sunscreen properties in the HEV, LEV, and infrared A range. However, tinted samples worked best in the blue light region, and the higher the wavelength range, the lower the protection.

Current Data on Effects of Long-Term Missions on the International Space Station on Skin Physiological Parameters.

BACKGROUND: Skin reaction to spaceflight has not really been studied yet, although the skin has a very important barrier function to protect the body and can contribute to a more general understanding of physiology. It is proposed here to make a more thorough investigation of the skin during long-term spaceflight, using noninvasive techniques. AIMS: The aim of the present Skin-B study is to investigate the kinetics and range of possible skin modifications during long-duration spaceflights and their recovery. METHODS: In order to investigate the effect on skin physiological parameters during spaceflight, measurements were carried out on 6 astronauts with respect to skin hydration, transepidermal water loss/barrier function, and surface evaluation of the living skin in orbit. Additional measured parameters on the ground were skin elasticity, skin density and thickness, as well as microcirculation. RESULTS: Data from the Skin-B subjects (n = 6) contradict the results obtained in the previous pilot study SkinCare (n = 1 subject). In the present study, no deterioration of the skin was found but rather an improvement in skin hydration and skin barrier function, and no changes or improvement in the appearance of the skin surface. Furthermore, the skin density and skin thickness as well as skin elasticity values were unchanged from pre-flight values. CONCLUSION: In conclusion, we found that spaceflight under present conditions has no negative impact on skin physiological parameters.

Determination of the Influence of the Antiphlogistic Ingredients Panthenol and Bisabolol on the SPF Value in vivo.

BACKGROUND: Today, the sun protection factor (SPF) value of sunscreen products is determined in vivo with a standardized protocol (EN ISO 24444:2010), and the measured SPF biological end point is the visible skin erythema. However, many of the sunscreen products currently available on the market have antiphlogistic ingredients, which may potentially result in an overestimated SPF of the sunscreen. AIMS: To investigate the potential influence of the antiphlogistic ingredients panthenol and bisabolol in sunscreens on the determined SPF value in vivo. METHODS: Formulations with different concentrations of the antiphlogistic ingredients bisabolol or panthenol were tested. As a reference, a base formulation (vehicle) without antiphlogistic ingredients was used. First, the SPF of the sunscreen formulas with and without antiphlogistic ingredients was analyzed in vitro. To investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the SPF was determined in vivo. Finally, selected formulations were also analyzed in an erythema model for testing formulations on UV-induced inflammation. RESULTS: It could be confirmed that no differences between the formula with and that without the active antiphlogistic ingredients bisabolol or panthenol exist when measured in vitro. However, there was also no statistically significant difference in the erythemal response between the vehicle (without an antiphlogistic active ingredient) and the test formulations with different concentrations of the antiphlogistic active ingredients in the in vivo determination of the SPF. Evidence of anti-inflammatory activity of the sunscreen antiphlogistics bisabolol and panthenol was also not apparent in the UV model over a time course of 48 h. Conlusion: The antiphlogistic ingredients panthenol and bisabolol incorporated in the tested sunscreen formula do not interfere with erythema reddening and thus do not affect the SPF value in vivo.

Multivariate binary classification of imbalanced datasets-A case study based on high-dimensional multiplex autoimmune assay data.

The classification of a population by a specific trait is a major task in medicine, for example when in a diagnostic setting groups of patients with specific diseases are identified, but also when in predictive medicine a group of patients is classified into specific disease severity classes that might profit from different treatments. When the sizes of those subgroups become small, for example in rare diseases, imbalances between the classes are more the rule than the exception and make statistical classification problematic when the error rate of the minority class is high. Many observations are classified as belonging to the majority class, while the error rate of the majority class is low. This case study aims to investigate class imbalance for Random Forests and Powered Partial Least Squares Discriminant Analysis (PPLS-DA) and to evaluate the performance of these classifiers when they are combined with methods to compensate imbalance (sampling methods, cost-sensitive learning approaches). We evaluate all approaches with a scoring system taking the classification results into consideration. This case study is based on one high-dimensional multiplex autoimmune assay dataset describing immune response to antigens and consisting of two classes of patients: Rheumatoid Arthritis (RA) and Systemic Lupus Erythemathodes (SLE). Datasets with varying degrees of imbalance are created by successively reducing the class of RA patients. Our results indicate possible benefit of cost-sensitive learning approaches for Random Forests. Although further research is needed to verify our findings by investigating other datasets or large-scale simulation studies, we claim that this work has the potential to increase awareness of practitioners to this problem of class imbalance and stresses the importance of considering methods to compensate class imbalance.

Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients.

BACKGROUND: Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. METHODS: Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. RESULTS: Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and CSRP2 (p>0.05), two, SPOP and ZNF671, close to statistical significance (p = 0.051 and 0.076). CONCLUSIONS: We provide evidence of an inflammation-specific autoantibody profile and confirm the expression of corresponding autoantigens in prostate tissue. This supports evaluation of autoantibodies as non-invasive markers for prostate inflammation.

Possible etiology of improvements in both quality of life and overlapping gastroesophageal reflux disease by proton pump inhibitor treatment in a prospective randomized controlled trial.

BACKGROUND: Symptoms suggestive of functional dyspepsia (FD) and irritable bowel syndrome (IBS) frequently overlap with those of gastroesophageal reflux disease. Despite the high prevalence of symptomatic overlap, the underlying etiology remains poorly defined. We assessed the correlation of symptomatic relief and health-related quality of life (HRQoL) with healing of reflux esophagitis to further derive insights into the underlying etiology. METHODS: 626 patients with reflux esophagitis were enrolled into one of two treatment groups (classical healing concept or the complete remission concept) to investigate differences in treatment intensity. Patients were treated with pantoprazole until esophageal mucosal healing. Remission was followed for up to 6 months without treatment. Gastro-intestinal symptoms and HRQoL were analyzed using disease-specific, psychometrically validated patient-reported outcome instruments (ReQuest™, GERDyzer™). RESULTS: Symptomatic burden reflected by ReQuest™ substantially decreased from baseline to end of treatment by 83% and 88% in either treatment group, respectively. ReQuest™ scores significantly decreased in patients with or without heartburn and in those with symptoms suggestive of FD and IBS, indicating response of all symptom categories to treatment (p < 0.005). Therapy-associated relief of symptoms was paralleled by substantial gains in HRQoL, which continued to stabilize post-treatment. CONCLUSIONS: Pantoprazole is effective in relieving upper and lower gastro-intestinal symptoms overlapping with erosive esophagitis, and provides sustained improvement in HRQoL post-treatment. Our results propose a link between both healing of erosive esophagitis and the slower remission of upper and lower gastro-intestinal symptoms. Since the improvement observed is likely to be multifactorial, the possibility for an immune-mediated etiology and identification of putative susceptibility factors by genome-wide association study may provide focus for future research. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00325676.

Predictive Factors in OCT Analysis for Visual Outcome in Exudative AMD.

Background. Reliable predictive factors for therapy outcome may enable treating physicians to counsel their patients more efficiently concerning probability of improvement or time point of discontinuation of a certain therapy. Methods. This is a retrospective analysis of 87 patients with exudative age-related macular degeneration who received three monthly intravitreal ranibizumab injections. Visual acuity before initiation of intravitreal therapy and 4-6 weeks after last intravitreal injection was compared and related to the preoperative visualisation of continuity of the outer retinal layers as assessed by OCT: external limiting membrane (ELM), inner photoreceptor segments (IPS), junction between inner and outer segments (IS/OS), and outer photoreceptor segments (OPS). Results. Visual acuity increased in 40 of 87 (46.0%) patients, it remained stable in 25 (28.7%), and 22 (25.3%) patients had decreased visual acuity four to six weeks after triple intravitreal ranibizumab injections. No statistically significant predictive value could be demonstrated for grade of continuity of outer retinal layers concerning visual acuity development. Conclusions. In our series of AMD patients, grade of continuity of outer retinal layers was not a significant predictive value for visual acuity development after triple ranibizumab injections.

Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test.

SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.

Rationale and design of the 'F.I.R.E.' study. A multicenter, double-blind, randomized, placebo-controlled study to measure the effect of FX06 (a fibrin-derived peptide Bbeta(15-42)) on ischemia-reperfusion injury in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

Immediate reopening of acutely occluded coronary arteries via primary percutaneous coronary intervention (PCI) is the treatment of choice to salvage the ischemic myocardium in the setting of ST-segment elevation myocardial infarction (STEMI). However, the sudden re-initiation of blood flow achieved with PCI can lead to a local acute inflammatory response with further endothelial and myocardial damage. This phenomenon, described as 'reperfusion injury', has been recognized for several decades, yet no pharmacologic intervention has so far succeeded in reducing myocardial damage linked to reperfusion. FX06 is a naturally occurring peptide derived from the neo-N-terminus of fibrin (Bbeta(15-42)). It prevents leukocyte migration through the gap junctions of endothelial cells. Experimental studies have shown that FX06 inhibits the binding of the proinflammatory fibrin E1 fragment to VE-cadherin expressed in the adherence junction. It represents a novel approach to reducing local and systemic inflammation, including myocardial reperfusion injury, in the adherens junction. The present multicenter, double-blind, randomized, placebo-controlled study is designed to test the hypothesis that FX06 injection during and immediately after primary PCI can reduce infarct size in patients with STEMI. The primary outcome measure of efficacy in this study is the degree of myocardial salvage calculated as the difference between the perfusion defect before and after PCI, determined by myocardial perfusion scintigraphy during rest. Further, infarct size at the end of the index hospitalization, as well as at 4 months, will be measured by cardiac magnetic resonance imaging. The present position paper describes the rationale, design and the methods utilized in this trial.