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The petroglyphs of the Negev Desert, Israel, are famous and valuable archaeological remains. Previous studies have investigated the microbial communities associated with petroglyphs and their potential role in stone deterioration; nevertheless, the role of fungi remains unclear. In this study, the fungal communities present on the stone and, as a comparison, in the surrounding environment (soil and air) at Negev petroglyph sites were analyzed by means of culture-dependent and -independent (metagenomic) techniques. The metagenomic results showed a high fungal biodiversity in the soil, and both approaches highlighted the prevalence of species producing melanized, large, thick-walled spores (mainly Alternaria spp.). From the air sampling, mostly Cladosporium spp. were retrieved. On the other hand, on the rock, the results seem to indicate a low presence of fungi, but with a rock-specialized mycobiota consisting of extremotolerant microcolonial fungi (MCF) (e.g., Vermiconidia and Coniosporium) and lichens (Flavoplaca). In addition, low proportions of cosmopolitan fungi were detected on the stone, but the comparison of the data clearly indicates that they are transients from the surrounding environment. The ability of the isolated strains to dissolve CaCO3 and therefore be a potential threat to the petroglyphs (limestone substrate) was tested, but only one strain resulted in positive acid production under laboratory conditions. Nevertheless, both lichens and MCF detected in this study are well-known stone deteriogens, which may have a significant impact on the petroglyph’s deterioration.

Age-associated remodeling processes affect the intramuscular connective tissue (IMCT) network, which may significantly impair muscle function. Thus, we aimed to test whether including exercises shown to efficiently target the IMCT to a conventional resistance exercise intervention (CONV) would result in greater functional gains as compared to CONV alone. Fifty-three men and women (66.2 ± 3.3 years) were assigned to either CONV (n = 15), multimodal training (MULTI; n = 17) or a control (CTRL; n = 21) group. All subjects were tested at baseline, and those assigned to CONV or MULTI underwent a 16-week training intervention. The CONV group followed a progressive resistance training program, in which the number of weekly training sessions gradually increased from 1 to 3. In the MULTI group, one of these sessions was replaced with plyometric training, followed by self-myofascial release. Testing included maximal strength and power, imaging-based muscle volume, architecture, and functional performance. The intervention effects were analyzed using two- or three-way repeated measures ANOVA models (α = 0.05). Briefly, the maximal knee extension isometric contraction, one-repetition maximum, and isokinetic peak torque increased in all groups (p

Fungi have always posed an unquestionable threat to heritage collections worldwide. Now, in a future of climate change, biological risk factors may have to be considered even more than before. Models and simulations to assess possible impacts a changing outdoor climate will have on indoor environments and, in turn, on biodeterioration are still underdeveloped and require a more substantial data basis. This study aimed at filling some of these knowledge gaps through a broad-based approach combining microclimatic and microbiological monitoring in four historic libraries in Austria with an uncontrolled indoor climate: Altenburg Abbey, Melk Abbey, Klosterneuburg Monastery and the Capuchin Monastery in Vienna. Data were generated from thermohygrometric sensors, cultivation-dependent air- and surface sampling and further surface dust sampling for cultivation-independent analyses. Results gave insights on the status quo of microbiological loads in the libraries and outdoor–indoor relationships. Influences of the geographic location and room-use on corresponding indoor fungal profiles were identified. Lower fungal diversities were found at the most rural site with the strongest climatic fluctuations and extreme values than in the most urban, sheltered library with a very stable climate. Further, the humidity-stabilizing potential of large collections of hygroscopic materials, such as books, was also examined. Implications for a sustainable approach to prevent future biodeterioration are discussed, supporting the long-term preservation of these valuable historic collections.

Abstract Background In RNA-sequencing studies a large number of hypothesis tests are performed to compare the differential expression of genes between several conditions. Filtering has been proposed to remove candidate genes with a low expression level which may not be relevant and have little or no chance of showing a difference between conditions. This step may reduce the multiple testing burden and increase power. Results We show in a simulation study that filtering can lead to some increase in power for RNA-sequencing data, too aggressive filtering, however, can lead to a decline. No uniformly optimal filter in terms of power exists. Depending on the scenario different filters may be optimal. We propose an adaptive filtering strategy which selects one of several filters to maximise the number of rejections. No additional adjustment for multiplicity has to be included, but a rule has to be considered if the number of rejections is too small. Conclusions For a large range of simulation scenarios, the adaptive filter maximises the power while the simulated False Discovery Rate is bounded by the pre-defined significance level. Using the adaptive filter, it is not necessary to pre-specify a single individual filtering method optimised for a specific scenario.

Background The COVID-19 pandemic has changed worldwide hygiene practices. In particular, the use of filtering face piece (FFP) masks markedly increased. Concerns have been raised regarding possible negative respiratory effects of wearing FFP masks. The aim of this study was to investigate gas exchange and subjective breathing effort in hospital personnel wearing FFP2 or FFP3 masks. Methods In this prospective, single-centre, crossover study, 200 hospital workers were assigned to alternately wear FFP2 or FFP3 masks for 1 h during routine activities. Capillary blood gas analysis was performed to evaluate gas exchange while wearing the FFP masks. The primary end-point was the change in capillary partial pressure of carbon dioxide (PcCO2). In addition, capillary partial pressure of oxygen (PcO2), respiratory rate and subjective breathing effort were assessed at the end of each hour. Changes between time points and study groups were estimated using univariate and multivariate models. Results PcCO2 increased from 36.8±3.5 to 37.2±3.3 mmHg (p=0.047) and 37.4±3.2 mmHg (p=0.003) in individuals wearing FFP2 or FFP3 masks, respectively. Age (p=0.021) and male sex (p

Introduction Increased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH30), the incidence of acute kidney injury, postoperative N-terminal probrain natriuretic peptide (NT-proBNP) concentrations and neurocognitive decline.Methods and analysis In this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH30 and NT-proBNP concentrations using linear or logistic regression models. We will measure inflammatory biomarkers before surgery, and on the first, second, third and fifth postoperative day. We will check medical records and conduct a telephone survey 30 days and 1 year after surgery. We evaluate neurocognitive function, using a Montreal Cognitive Assessment, before and 1 year after surgery.Ethics and dissemination This study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21).Trial registration number NCT04753307.

BackgroundSupplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate.MethodsWe present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate.ResultsThere was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate −0.16 mmHg, CI –1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min−1 [58, 72], and in the 30% oxygen group: 64 beats.min−1 [58; 70]; effect estimate: 0.12 beats.min−1, CI –2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected.ConclusionIn contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients.Clinical Trail Registrationhttps://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1

Abstract A high number of trauma patients are under the influence of alcohol. Since many of them need immediate surgical procedures, it is imperative to be aware of the interaction of alcohol with general anesthesia. To counter challenges that arise from clinical studies, we designed an animal experiment in which 48 adult Wistar rats either received 1 g · kg−1 ethanol, 2 g · kg−1 ethanol or placebo via intraperitoneal application. Subsequently, they were anesthetized with an individual concentration of sevoflurane. The minimum alveolar concentration (MAC) of the different groups was assessed using Dixon’s up-and-down design and isotonic regression methods. The bootstrap estimate of the MAC of sevoflurane in the placebo group was 2.24 vol% (95% CI 1.97–2.94 vol%). In the low dose ethanol group, the bootstrap estimate was 1.65 vol% (95% CI 1.40–1.98 vol%), and in the high dose ethanol group, it was 1.08 vol% (95% CI 0.73–1.42 vol%). We therefore report that intraperitoneal application of 1 g · kg−1 or 2 g · kg−1 ethanol both resulted in a significant reduction of the MAC of sevoflurane in adult Wistar rats: by 26.3% and 51.8% respectively as compared to placebo.

Purpose. The aim of the study is to analyze the swept source-optical coherence tomography angiography (SS-OCTA) characteristics of polypoidal lesions in Caucasian patients. Methods. In this retrospective observational case series, 43 polypoidal lesions in 32 eyes of 32 patients were diagnosed using indocyanine green angiography (ICGA) and compared to SS-OCTA at a tertiary medical retina center (Clinic Landstraße, Vienna Healthcare Group, Austria) between June 2017 and March 2020. Vascularity was identified by color-coded B-scan SS-OCTA while morphology was described as revealed by en face SS-OCTA after alignment with ICGA-confirmed findings. Results. In total, SS-OCTA detected all polypoidal lesions, as identified by ICGA. On B-scan SS-OCTA, circumscribed flow was detected in 33 (76.7%) polypoidal lesions and diffuse flow in 10 (23.3%) lesions. On en face SS-OCTA, polypoidal lesions appeared morphologically as 19 tangled vessel balls (44.2%), 6 tangled vessel balls next to dilated vessels (13.9%), 8 vascular dilatations (18.6%), and 8 ill-defined vascular networks (18.6%), leaving 2 lesions (4.6%) undetected. Circumscribed flow was significantly associated with tangled vessel balls (p=0.005). Conclusion. This study highlights the importance of a multimodal imaging approach, including SS-OCTA, for the evaluation of polypoidal lesions. Our findings suggest a morphological heterogeneity of vascular patterns in Caucasian patients with polypoidal lesions, as pictured by SS-OCTA.

BackgroundPregabalin is commonly used perioperatively to reduce post-operative pain and opioid consumption and to prevent the development of chronic pain. It has been shown to reduce anesthetic consumption in balanced anesthesia, but studies investigating its effect on the minimum alveolar concentration (MAC) of volatile anesthetics are lacking. The aim of this study was to investigate the effect of two different doses of pregabalin on the MAC of sevoflurane.MethodsIn a randomized, double-blinded, placebo controlled clinical study, 75 patients were assigned to receive placebo, 300 mg pregabalin, or 150 mg pregabalin, as a capsule 1 h before anesthesia induction with sevoflurane only. After equilibration, the response to skin incision (movement vs. non-movement) was monitored. The MAC was assessed using an up- and down-titration method.ResultsThe MAC of sevoflurane was estimated as 2.16% (95% CI, 2.07–2.32%) in the placebo group, 1.44% (95% CI, 1.26–1.70%) in the 300 mg pregabalin group, and 1.81% (95% CI, 1.49–2.13%) in the 150 mg pregabalin group. We therefore report a 33% reduction in the MAC of sevoflurane in the 300 mg pregabalin group as compared to placebo. The MAC of the 150 mg pregabalin group was reduced by 16% as compared to placebo but was not statistically significant.ConclusionsThe administration of 300 mg pregabalin reduced the MAC of sevoflurane by 33%, while the administration of 150 mg pregabalin did not significantly reduce the MAC of sevoflurane. Pregabalin use led to a small reduction in post-operative pain levels but increased side effects in a dose-dependent manner.

Benefits from EV (Electric vehicles) and e-mobility include the reduction of local emissions of pollutants from particulate matter (PM0.5, PM5, and PM10) and nitrogen oxides (NOx and NO2). Cities and urban agglomerations benefit the most from potential emission reductions from EVs due to the large number of cars utilized in most urban traffic systems. This abstract presents results from a corporate research and funding project in Baden-Wuerttemberg, Germany (LINOx BW) which facilitates the installation of 2358 charging points within 178 different sub-projects in 23 different cities, spanning a period of four years. Utilizing several different survey waves, data about outgoing currents from these publicly funded charging points are gathered. Converting this data utilizing car classifications and emission classes (HBEFA), the reduction of local nitrogen oxides is derived.

Abstract Background Type 2 macular neovascularization (MNV) is supposed to be a rare condition in age-related macular degeneration (AMD). The main purpose of this study was to assess accompanying factors of type 2 MNV in AMD. Methods Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging. Results Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen

Petroglyph sites exist all over the world. They are one of the earliest forms of mankind’s expression and a precursor to art. Despite their outstanding value, comprehensive research on conservation and preservation of rock art is minimal, especially as related to biodeterioration. For this reason, the main objective of this study was to explore the factors involved in the degradation of petroglyph sites in the Negev desert of Israel, with a focus on biodegradation processes. Through the use of culture-independent microbiological methods (metagenomics), we characterized the microbiomes of the samples, finding they were dominated by bacterial communities, in particular taxa of Actinobacteria and Cyanobacteria, with resistance to radiation and desiccation. By means of XRF and Raman spectroscopies, we defined the composition of the stone (calcite and quartz) and the dark crust (clay minerals with Mn and Fe oxides), unveiling the presence of carotenoids, indicative of biological colonization. Optical microscopy and SEM–EDX analyses on thin sections highlighted patterns of weathering, possibly connected to the presence of biodeteriorative microorganisms that leach the calcareous matrix from the bedrock and mobilize metal cations from the black varnish for metabolic processes, slowly weathering it.

Purpose. To evaluate the capability of swept source-optical coherence tomography angiography (SS-OCTA) in the detection and localization of treatment-naive macular neovascularization (MNV) secondary to exudative neovascular age-related macular degeneration (nAMD). Methods. In this prospective, observational case series, 158 eyes of 142 patients were diagnosed with exudative nAMD using fluorescein (FA) and indocyanine green angiography (ICGA) and evaluated by SS-OCTA in a tertiary retina center (Rudolf Foundation Hospital Vienna, Austria). The main outcome measure was the sensitivity of SS-OCTA compared to the standard multimodal imaging approach. Secondary outcome measure was the anatomic analysis of MNV in relation to the retinal pigment epithelium. Results. En-face SS-OCTA confirmed a MNV in 126 eyes (sensitivity: 79.8%), leaving 32 eyes (20.2%) undetected. In 23 of these 32 eyes (71.9%), abnormal flow in cross-sectional SS-OCTA B-scans was identified, giving an overall SS-OCTA sensitivity of 94.3%. Eyes with a pigment epithelium detachment (PED) ≥ 300 μm had a smaller probability for correct MNV detection (p=0.015). Type 1 MNV showed a trend (p=0.051) towards smaller probability for the correct detection compared to all other subtypes. Other relevant factors for the nondetection of MNV in SS-OCTA were image artifacts present in 3 of 32 eyes (9.4%). SS-OCTA confirmed the anatomic localization of 93 in 126 MNVs as compared to FA (sensitivity: 73.8%). There was no influence of age, gender, pseudophakia, visual acuity, central foveal thickness, or subfoveal choroidal thickness on the detection rate of MNV. Conclusions. SS-OCTA remains inferior to dye-based angiography in the detection rate of exudative nAMD consistent with type 1 MNV and a PED ≥300 µm. The capability to combine imaging modalities and distinguish the respective MNV subtype improves its diagnostic value.

Seven emblematic Leonardo da Vinci’s drawings were investigated through third generation sequencing technology (Nanopore). In addition, SEM analyses were carried out to acquire photographic documentation and to infer the nature of the micro-objects removed from the surface of the drawings. The Nanopore generated microbiomes can be used as a “bio-archive” of the drawings, offering a kind of fingerprint for current and future biological comparisons. This information might help to create a biological catalog of the drawings (cataloging), a microbiome-fingerprint for each single analyzed drawing, as a reference dataset for future studies (monitoring) and last but not least a bio-archive of the history of each single object (added value). Results showed a relatively high contamination with human DNA and a surprising dominance of bacteria over fungi. However, it was possible to identify typical bacteria of the human microbiome, which are mere contaminants introduced by handling of the drawings as well as other microorganisms that seem to have been introduced through vectors, such as insects and their droppings, visible through the SEM analyses. All drawings showed very specific bio-archives, but a core microbiome of bacteria and fungi that are repeatedly found in this type of material as true degraders were identified, such as members of the phyla Proteobacteria, Actinobacteria, and Firmicutes among bacteria, and fungi belonging to the classes Sordariomycetes and Eurotiomycetes. In addition, some similarities were observed that could be influenced by their geographical location (Rome or Turin), indicating the influence of this factor and denoting the importance of environmental and storage conditions on the specific microbiomes.

Purpose. To evaluate 7-year visual and anatomical outcomes of intravitreal injections (IVI) with antivascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD) based on a personalized pro re nata (PRN) regimen. Methods. Anonymized data of 124 consecutive eyes in 121 patients with treatment-naïve nAMD were initially collected in 2010. Of those, 45 received anti-VEGF IVI at least every 6months until 2017 in one single center in Austria and hence were retrospectively analyzed. All eyes had been initiated on a loading dose of 3 monthly IVI with different anti-VEGF agents followed by a PRN regimen in the first year. At year 2, monitoring as well as therapeutic intervention could be prolonged every 2weeks up to intervals of 3months without capping treatment. Primary outcome measure was the change of visual acuity (VA) assessed by Early Treatment Diabetic Retinopathy Study charts at 4 meters (ETDRS) in letters—counting every correctly read letter—and converted to Snellen. Secondary outcome measures were number of injections and change of central retinal thickness (CMT) from baseline. Results. Mean baseline VA was 20/63 + 1 (0.63 ± 0.26 ETDRS) and declined to 20/100 + 2 (0.45 ± 0.33) with an overall loss of 9 letters ETDRS after 7years (p = 0.001). An average of 3.5 ± 1.9 IVI was given per year and eye. Mean CMT at baseline was 322 ± 95 μm, decreased by 52 μm to 270 ± 70 μm within the first year, and remained below baseline at year 7 (271 ± 106 μm; p

Abstract Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. This paper summarizes the main results of the project, which was completed in 2017. The InSPiRe project has led to development of novel statistical methodology for clinical trials in small populations in four areas. We have explored new decision-making methods for small population clinical trials using a Bayesian decision-theoretic framework to compare costs with potential benefits, developed approaches for targeted treatment trials, enabling simultaneous identification of subgroups and confirmation of treatment effect for these patients, worked on early phase clinical trial design and on extrapolation from adult to pediatric studies, developing methods to enable use of pharmacokinetics and pharmacodynamics data, and also developed improved robust meta-analysis methods for a small number of trials to support the planning, analysis and interpretation of a trial as well as enabling extrapolation between patient groups. In addition to scientific publications, we have contributed to regulatory guidance and produced free software in order to facilitate implementation of the novel methods.

Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called “cytokine storm”, with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19.

The aim of this prospective study was to assess lymphocyte proliferative and cytokine response prior to and following tick-borne encephalitis (TBE) immunization among patients after allogeneic hematopoietic stem cell transplantation (HSCT). Seventeen adult patients 11–13 months after HSCT and eight unvaccinated healthy adults received up to three TBE vaccinations. Following in vitro stimulation with TBE-antigen, lymphocyte proliferation and cytokine secretion (IL-2, IL-10, IL-13, TNF-alpha, IFN-gamma, GM-CSF) were analyzed by thymidine incorporation assay and the Luminex system. Ten patients (59%) showed significant baseline TBE-specific lymphocyte proliferation (stimulation index (SI) > 3) prior to vaccination, but none of the unvaccinated controls (p = 0.002). All patients with a TBE-specific antibody response after two vaccinations (at least 2-fold increase of neutralization test titers) exhibited a strong TBE-specific lymphocyte proliferative response at baseline (SI > 10). Patients with sibling donors had a significantly stronger baseline TBE-specific lymphocyte proliferative and IL-13 cytokine response than patients with unrelated donors (p < 0.05). In conclusion, a relevant proportion of patients showed TBE-specific lymphocyte proliferative and cytokine responses prior to vaccination after HSCT, which predicted the humoral response to the vaccine. Patients with vaccinated sibling donors were more likely to elicit a cellular immune response than patients with unrelated donors of unknown vaccination status.

Abstract Developing effective therapies against chronic wound healing deficiencies is a global priority. Thus we evaluated the safety of two different doses of topically administered autologous APOSEC, the secretome of apoptotic peripheral blood mononuclear cells (PBMCs), in healthy male volunteers with artificial dermal wounds. Ten healthy men were enrolled in a single-center, randomized, double-blinded, placebo-controlled phase 1 trial. Two artificial wounds at the upper arm were generated using a 4-mm punch biopsy. Each participant was treated with both topically applied APOSEC and placebo in NuGel for 7 consecutive days. The volunteers were randomized into two groups: a low-dose group (A) receiving the supernatant of 12.5 × 106 PBMCs and a high-dose group (B) receiving an equivalent of 25 × 106 PBMCs resuspended in NuGel Hydrogel. Irradiated medium served as placebo. The primary outcome was the tolerability of the topical application of APOSEC. All adverse events were recorded until 17 days after the biopsy. Local tolerability assessment was measured on a 4-point scale. Secondary outcomes were wound closure and epithelization at day 7. No therapy-related serious adverse events occurred in any of the participants, and both low- and high-dose treatments were well tolerated. Wound closure was not affected by APOSEC therapy.

An amendment to this paper has been published and can be accessed via the original article.

Purpose. To assess the relationship between signs of activity in exudative neovascular age-related macular degeneration (nAMD) following anti-vascular endothelial growth factor (anti-VEGF) treatment and morphology of choroidal neovascularization (CNV) based on neovascular density as imaged using swept source-optical coherence tomography angiography (SS-OCTA) in a qualitative manner. Methods. A single-cohort retrospective data analysis from one tertiary eye care center. Seventy-seven eyes of 72 patients were included and their charts reviewed which had been started on intravitreal injections with anti-VEGF for nAMD at least one year prior to enrollment. Clinically active disease was evaluated by slit-lamp fundus examination and spectral domain-OCT B-scans. Morphological appearance in SS-OCTA was characterized based on 5 different criteria and subsequently divided into 3 groups: predominantly hyperdense, minimally hyperdense, and hypodense lesions. Results. Fifty-eight eyes (75%) were considered clinically active and 19 eyes (25%) clinically inactive. CNV was depicted in 71 eyes (92%) by SS-OCTA and separated accordingly into predominantly hyperdense (32%), minimally hyperdense (34%), and hypodense lesions (34%). A borderline significant difference in the probability of neovascular activity for predominantly hyperdense lesions compared to hypodense lesions was detected (p=0.05). Conclusions. Hyperdense choroidal neovascularization based on qualitative assessment of flow density showed a significant relation to active disease. Inactivity could not be matched adequately. This study demonstrated the potential usefulness of SS-OCTA for guidance of treatment in age-related macular degeneration.

With advancing age, the skeletal muscle extracellular matrix (ECM) undergoes fibrotic changes that may lead to increased muscle stiffness, injury susceptibility and strength loss. This study tested the potential of different exercises to counter these changes by stimulating the activity of genes associated with ECM remodeling. Twenty-six healthy men (66.9 ± 3.9 years) were stratified to two of four groups, performing unilateral (i) conventional resistance exercise, (ii) conventional resistance exercise followed by self-myofascial release (CEBR), (iii) eccentric-only exercise (ECC) or (iv) plyometric jumps (PLY). The non-trained leg served as control. Six hours post-exercise, vastus lateralis muscle biopsy samples were analyzed for the expression of genes associated with ECM collagen synthesis (COL1A1), matrix metallopeptidases (collagen degradation; MMPs) and peptidase inhibitors (TIMP1). Significant between-group differences were found for MMP3, MMP15 and TIMP1, with the greatest responses in MMP3 and TIMP1 seen in CEBR and in MMP15 in ECC. MMP9 (3.24–3.81-fold change) and COL1A1 (1.47–2.40-fold change) were increased in CEBR and PLY, although between-group differences were non-significant. The expression of ECM-related genes is exercise-specific, with CEBR and PLY triggering either earlier or stronger remodeling than other stimuli. Training studies will test whether execution of such exercises may help counter age-associated muscle fibrosis.

AIMS:Our aim was to evaluate, in a second data analysis of the prospective randomized controlled trial conducted by Austrian Urogynaecology Working Group, the effect of age, BMI and parity at the time of surgery on short- and long-term outcomes of women primarily treated for SUI (stress urinary incontinence) with midurethral slings. METHODS:In the original study 554 patients received randomly a retropubic (TVT) or a transobturator midurethral (TVT-O) sling procedure. 480 (87%) and 277 (50%) patients were available for a follow-up efficacy evaluation at 3 months and 5 years respectively. RESULTS:Higher age and BMI at surgery appear to lead to a larger probability to have a positive stress test 5 years after surgery, but not after 3 months. Older patients seem to have a worse perception of improvement 5 years after surgery as compared to younger ones, as described by the PGI-I score. Age and BMI do not affect significantly the quality of life of women surgically treated for SUI, as reflected by the results of King´s Health Questionnaire. Parity does not seem to have any effect on objective and subjective surgical outcomes. CONCLUSIONS:Higher age and BMI at surgery have a detrimental influence on the objective cure rate at 5 years after midurethral sling surgery; higher age also has a negative influence on subjective long-term outcomes. However, these demographic parameters do not influence significantly the quality of life of patients after anti-incontinence surgery. Parity does not show any significant influence on success rate of midurethral sling.

Central processes in the pathogenesis of TAV- (tricuspid aortic valve) and BAV- (bicuspid aortic valve) associated ascending thoracic aortic aneurysm (ATAA) development are still unknown. To gain new insights, we have collected aortic tissue and isolated smooth muscle cells of aneurysmal tissue and subjected them to in situ and in vitro analyses. We analyzed aortic tissue from 78 patients (31 controls, 28 TAV-ATAAs, and 19 BAV-ATAAs) and established 30 primary smooth muscle cell cultures. Analyses included histochemistry, immuno-, auto-fluorescence-based image analyses, and cellular analyses including smooth muscle cell contraction studies. With regard to TAV associated aneurysms, we observed a strong impairment of the vascular wall, which appears on different levels—structure and dimension of the layers (reduced media thickness, increased intima thickness, atherosclerotic changes, degeneration of aortic media, decrease of collagen, and increase of elastic fiber free area) as well as on the cellular level (accumulation of fibroblasts/myofibroblasts, and increase in the number of smooth muscle cells with a reduced alpha smooth muscle actin (α-SM actin) content per cell). The pathological changes in the aortic wall of BAV patients were much less pronounced—apart from an increased expression of osteopontin (OPN) in the vascular wall which stem from smooth muscle cells, we observed a trend towards increased calcification of the aortic wall (increase significantly associated with age). These observations provide strong evidence for different pathological processes and different disease mechanisms to occur in BAV- and TAV-associated aneurysms.

BackgroundThe prognostic significance of tricuspid regurgitation (TR) and right ventricular (RV) function in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) is unknown. The aim of the present study was to evaluate the impact of TR and RV systolic dysfunction on early and late mortality in this setting.MethodsThis was a prospective single-center observational study. 465 consecutive patients who were referred to AVR for severe AS were investigated. Significant TR was defined as TR≥moderate by transthoracic echocardiography.ResultsAt baseline, significant TR was present in 26 (5.6%) patients. Patients with TR presented with a higher EuroSCORE I (p = 0.001), a higher incidence of previous cardiac surgery (pConclusionsTR, RV dysfunction, age, and concomitant CABG are associated with outcome in patients undergoing AVR for severe AS. This finding underlines the importance of a thorough echocardiographic evaluation with particular consideration of the right heart in these patients.

Objective"Patient-prosthesis mismatch" (PPM) after aortic valve replacement (AVR) has been reported to increase morbidity and mortality. Although algorithms have been developed to avoid PPM, factors favouring its occurrence have not been well defined.Design and settingThis was a prospective cohort study performed at the Medical University of Vienna.Patients361 consecutive patients who underwent aortic valve replacement for isolated severe aortic stenosis were enrolled.Main outcome measuresPatient- as well as prosthesis-related factors determining the occurrence of moderate and severe PPM (defined as effective orifice area indexed to body surface area ≤ 0.8 cm(2)/m(2)) were studied.ResultsPostoperatively, 172 patients (48%) were diagnosed with PPM. The fact that predominantly female patients were affected (58% with PPM diagnosis in women versus 36% in men, pConclusionsThe occurrence of PPM is determined by aortic root diameter and prosthesis type. Novel sutureless bioprostheses with optimized hemodynamic performance or transcatheter aortic valves may become a promising alternative to conventional bioprosthetic valves in the future.

The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding.