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Extracting microplastics from complex matrices poses challenges due to the potential impact of harsh chemical treatments on microplastic properties. For fate and hazard assessment reliable techniques are needed to not only quantify the particle number but also to assess the physicochemical properties of environmental microplastics with minimum changes induced by extraction. Here we present the method development for an innovative and non-destructive extraction protocol based on a switchable calcium chloride density separation column. In contrast to commonly reported extraction protocols, the presented technique is suitable for targeted microplastic property analysis (e.g., surface chemistry and texture) by keeping chemical treatments (such as oxidation and enzymatic digestion) to a minimum. By adjusting the temperature we can control the aggregate state of the highly concentrated salt solution, allowing to separate the microplastics from matrix by cutting of purified, solidified samples. Harsh chemical treatments are avoided, as well as obstruction of microplastic extraction by adsorption to matrix components when passing the tap at the bottom of traditional density separation funnels.The use of microplastics that were prelabeled with a fluorescence dye helped to solve difficulties observed during method development by visual inspection before measurement of extraction efficiency: We spiked a blank compost with low-density polyethylene (LDPE) and polyamide (PA). Additionally, UV aged LDPE was used to demonstrate applicability to more hydrophilic, more environmentally relevant microplastics. The obtained initial results show high recovery of both unaged and aged LDPE over 97 wt.-% and an efficient compost removal but a lower and less robust recovery (between 68 and 18 wt.-%) for PA particles that are more challenging to extract due to an unfortunate synergistic combination of smaller particle size and higher density. Method adaptation to other microplastic types may still be necessary. In short: • A low-cost and simple approach without oxidation to extract (pre-aged) microplastics from compost • Method development by visual observation using fluorescent labelled microplastics and method validation by spike-recovery tests

Understanding the occurrence and transformation of microplastics when released into the environment is essential for risk assessment. The use of biodegradable polymers in agriculture can help to reduce microplastic accumulation in soil, since released fragments of such materials are not persistent and are further transformed into CO2 and biomass (Wohlleben et al., 2023). To be able to monitor the fragmentation and biodegradation of these materials in soil, a validated extraction protocol is needed, which does not induce changes in the chemical and particle properties, additionally it should show high recoveries and matrix removal efficiency. A density-based extraction method in the centrifuge has the potential to remove a high amount of the soil matrix and is very selective for the polymer at the same time. Here we developed an efficient and non-destructive extraction protocol for biodegradable fragments from different soils using sequential centrifugation steps with varying densities and a freezing approach for sample collection. Although the focus of the present study was on biodegradable fragments, the technique can also be used for other types of microplastics with similar or lower density than the one tested for the method validation, but additional recovery tests for the target analyte are recommended. • A density-based extraction method for microplastics from soil, validated by recovery and stability tests using biodegradable polymers • Vessel changes and harsh chemical treatments are kept to a minimum

Background: Team handball involves a tremendous amount of shoulder motion with high forces during repeated extended external range of motion. This causes shoulder complaints and overuse injuries. While eccentric training for the lower extremity shows preventive effects by improving strength, range of motion and fascicle length, there is a research gap for the shoulder joint and for advanced tissue characterization using diffusion tensor imaging.Objectives: To investigate the effects of 6-week eccentric isokinetic resistance training on strength, flexibility, and fiber architecture characteristics of the external rotators compared to an active control group in junior male handball players.Methods: 15 subjects were randomly assigned to the eccentric training group and 14 subjects to the active control group (conventional preventive training). Primary outcome measures were eccentric and concentric isokinetic strength of the external rotators, range of motion, and muscle fascicle length and fascicle volume.Results: The intervention group, showed significant changes in eccentric strength (+15%). The supraspinatus and infraspinatus muscles showed significant increases in fascicle length (+13% and +8%), and in fractional anisotropy (+9% and +6%), which were significantly different from the control group.Conclusion: Eccentric isokinetic training has a significant effect on the function and macroscopic structure of the shoulder external rotators in male junior handball players. While strength parameters and muscle structure improved, range of motion did not change. This research helps understanding the physiology of muscle and the role of eccentric training on shoulder function and muscle structure. Furthermore, DTI was found to be a promising tool for advanced tissue characterization, and the in vivo derived data can also serve as model input variables and as a possibility to extend existing ex-vivo muscle models. Future research is needed for functional and structural changes following convenient eccentric field exercises.

Background Stent thrombosis is a rare but deleterious event. Routine coronary angiography with percutaneous coronary intervention (PCI) is often deferred in the presence of laboratory markers of acute inflammation to prevent complications. The aim of this study was to investigate whether an acute inflammatory state is associated with an increased risk of early stent thrombosis. Methods and Results Within a prospective single‐center registry, the association between preprocedural acute inflammatory activation, defined as C‐reactive protein plasma levels >50 mg/L or a leukocyte count >12 g/L, and occurrence of early (≤30 days) stent thrombosis was evaluated. In total, 11 327 patients underwent PCI and of those, 6880 patients had laboratory results available. 49.6% of the study population received PCI for an acute coronary syndrome and 50.4% for stable ischemic heart disease. In patients with signs of acute inflammatory activation (24.9%), PCI was associated with a significantly increased risk for stent thrombosis (hazard ratio, 2.89; P

Abstract The Serappis (SEarch for RAre PP-neutrinos In Scintillator) project aims at a precision measurement of the flux of solar pp neutrinos on the few-percent level. Such a measurement will be a relevant contribution to the study of solar neutrino oscillation parameters and a sensitive test of the equilibrium between solar energy output in neutrinos and electromagnetic radiation (solar luminosity constraint). The concept of Serappis relies on a small organic liquid scintillator detector ( $$\sim $$ ∼ 20 m $$^3$$ 3 ) with excellent energy resolution ( $$\sim $$ ∼ 2.5% at 1 MeV), low internal background and sufficient shielding from surrounding radioactivity. This can be achieved by a minor upgrade of the OSIRIS facility at the site of the JUNO neutrino experiment in southern China. To go substantially beyond current accuracy levels for the pp flux, an organic scintillator with ultra-low $$ {^{14}\hbox {C}}$$ 14 C levels (below $$10^{-18}$$ 10 - 18 ) is required. The existing OSIRIS detector and JUNO infrastructure will be instrumental in identifying suitable scintillator materials, offering a unique chance for a low-budget high-precision measurement of a fundamental property of our Sun that will be otherwise hard to access.

Abstract Background In 2014, we first described novel autoantibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1-IgG/anti-Sj) in patients with autoimmune cerebellar ataxia (ACA) in this journal. Here, we provide a review of the available literature on ITPR1-IgG/anti-Sj, covering clinical and paraclinical presentation, tumour association, serological findings, and immunopathogenesis. Methods Review of the peer-reviewed and PubMed-listed English language literature on ITPR1-IgG/anti-Sj. In addition, we provide an illustrative report on a new patient with ITPR1-IgG-associated encephalitis with cognitive decline and psychosis. Results So far, at least 31 patients with serum ITPR1-IgG/anti-Sj have been identified (clinical information available for 21). The most common manifestations were ACA, encephalopathy with seizures, myelopathy, and (radiculo)neuropathy, including autonomic neuropathy. In 45% of cases, an underlying tumour was present, making the condition a facultative paraneoplastic neurological disorder. The neurological syndrome preceded tumour diagnosis in all but one case. In most cases, immunotherapy had only moderate or no effect. The association of ITPR1-IgG/anti-Sj with manifestations other than ACA is corroborated by the case of a 48-year-old woman with high-titre ITPR1-IgG/anti-Sj antibodies and rapid cognitive decline, affecting memory, attention and executive function, and psychotic manifestations, including hallucinations, investigated here in detail. FDG-PET revealed right-temporal glucose hypermetabolism compatible with limbic encephalitis. Interestingly, ITPR1-IgG/anti-Sj mainly belonged to the IgG2 subclass in both serum and cerebrospinal fluid (CSF) in this and further patients, while it was predominantly IgG1 in other patients, including those with more severe outcome, and remained detectable over the entire course of disease. Immunotherapy with intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulins, was repeatedly followed by partial or complete recovery. Long-term treatment with cyclophosphamide was paralleled by relative stabilization, although the patient noted clinical worsening at the end of each treatment cycle. Conclusions The spectrum of neurological manifestations associated with ITPR1 autoimmunity is broader than initially thought. Immunotherapy may be effective in some cases. Studies evaluating the frequency of ITPR1-IgG/anti-Sj in patients with cognitive decline and/or psychosis of unknown aetiology are warranted. Tumour screening is essential in patients presenting with ITPR1-IgG/anti-Sj.

Abstract We study damping signatures at the Jiangmen Underground Neutrino Observatory (JUNO), a medium-baseline reactor neutrino oscillation experiment. These damping signatures are motivated by various new physics models, including quantum decoherence, ν 3 decay, neutrino absorption, and wave packet decoherence. The phenomenological effects of these models can be characterized by exponential damping factors at the probability level. We assess how well JUNO can constrain these damping parameters and how to disentangle these different damping signatures at JUNO. Compared to current experimental limits, JUNO can significantly improve the limits on τ 3/m 3 in the ν 3 decay model, the width of the neutrino wave packet σ x , and the intrinsic relative dispersion of neutrino momentum σ rel.

PURPOSEFontan procedure and its modifications are the preferred approach to definitive palliation in uni- ventricular hearts though often with short-term or long-term complications. It is believed that a dysfunction in lymphatic circulation is responsible for part of the complications. Occasionally, abnormal supraclavicular lymphatic vessel convolutes can be observed in contrast-enhanced magnetic resonance angiography (ceMRA). This study aims to determine the frequency of this phenomenon as well as a possible correlation with the functional status after Fontan procedure.METHODSCeMRA of 37 patients after Fontan surgery was retrospectively screened and grouped for the presence or absence of abnormal lymphatic convolute. An attempt was made to identify differ- ences in the level of dysfunction of the Fontan circulation between the 2 groups.RESULTSIn 6 of 37 patients (16%), an abnormal cervical lymphatic convolute was found in the cervical venous angle. The surrogate parameters for a malfunction of the Fontan circulation did not sig- nificantly differ between both groups.CONCLUSIONThis is the first description of cervical lymphatic vessels in Fontan patients enhancing incidentally in ceMRA, probably due to venous-to-lymphatic reflux. As the likelihood of various complica- tions of Fontan circulation increases with the severity of lymphatic dysfunction, this observation could help to select patients who require closer monitoring or advanced lymphatic imaging.

The ability of muscle to generate force depends on its architecture and health condition. MR-based diffusion tensor imaging of muscle (mDTI) is an innovative approach for showing the fiber arrangement for the whole muscle volume. For accurate calculations of fiber metrics, muscle segmentation prior to tractography is regarded as necessary. Since segmentation is known to be operator dependent, it is important to understand how segmentation affects tractography. The aim of this study was to compare the results of deterministic fiber tracking based on muscle models generated by two independent operators. In addition, this study compares the results with a segmentation-free approach. Fifteen subjects underwent mDTI of the right shoulder. The results showed that mDTI can be successfully applied to complex joints such as the human shoulder. Furthermore, operator segmentation did not influence the results of fiber tracking and fascicle length (FL), fiber volume (FV), fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) showed excellent intraclass correlation estimates (≥ 0.975). As an exploratory approach, the segmentation-free fiber tracking showed significant differences in terms of mean fascicle length. Based on these findings, we conclude that tractography is not sensitive to small deviations in muscle segmentation. Furthermore, it implies that mDTI and automatic segmentation approaches or even a segmentation-free analysis can be considered for evaluation of muscle architecture.

Tensiomyography (TMG) is a non-invasive method for measuring contractile properties of skeletal muscle that is increasingly being used in research and practice. However, the lack of standardization in measurement protocols mitigates the systematic use in sports medical settings. Therefore, this study aimed to investigate the effects of lower leg fixation and sensor location on TMG-derived parameters. Twenty-two male participants underwent TMG measurements on the m. biceps femoris (BF) in randomized order with and without lower leg fixation (fixed vs. non-fixed). Measurements were conducted at 50% of the muscle's length (BF-mid) and 10 cm distal to this (BF-distal). The sensor location affected the contractile properties significantly, both with and without fixation. Delay time (Td) was greater at BF-mid compared to BF-distal (fixed: 23.2 ± 3.2 ms vs. 21.2 ± 2.7 ms, p = 0.002; non-fixed: 24.03 ± 4.2 ms vs. 21.8 ± 2.7 ms, p = 0.008), as were maximum displacement (Dm) (fixed: 5.3 ± 2.7 mm vs. 3.5 ± 1.7 mm, p = 0.005; non-fixed: 5.4 ± 2.5 mm vs. 4.0 ± 2.0 mm, p = 0.03), and contraction velocity (Vc) (fixed: 76.7 ± 25.1 mm/s vs. 57.2 ± 24.3 mm/s, p = 0.02). No significant differences were revealed for lower leg fixation (all p > 0.05). In summary, sensor location affects the TMG-derived parameters on the BF. Our findings help researchers to create tailored measurement procedures in compliance with the individual goals of the TMG measurements and allow adequate interpretation of TMG parameters.

(1) Background: In the oral environment, sound enamel and dental restorative materials are immediately covered by a pellicle layer, which enables bacteria to attach. For the development of new materials with repellent surface functions, information on the formation and maturation of salivary pellicles is crucial. Therefore, the present in situ study aimed to investigate the proteomic profile of salivary pellicles formed on different dental composites. (2) Methods: Light-cured composite and bovine enamel samples (controls) were exposed to the oral cavity for 30, 90, and 120 min. All samples were subjected to optical and mechanical profilometry, as well as SEM surface evaluation. Acquired pellicles and unstimulated whole saliva samples were analyzed by SELDI–TOF–MS. The significance was determined by the generalized estimation equation and the post-hoc bonferroni adjustment. (3) Results: SEM revealed the formation of homogeneous pellicles on all test and control surfaces. Profilometry showed that composite surfaces tend to be of higher roughness compared to enamel. SELDI–TOF–MS detected up to 102 different proteins in the saliva samples and up to 46 proteins in the pellicle. Significant differences among 14 pellicle proteins were found between the composite materials and the controls. (4) Conclusions: Pellicle formation was material- and time-dependent. Proteins differed among the composites and to the control.

Abstract The OSIRIS detector is a subsystem of the liquid scintillator filling chain of the JUNO reactor neutrino experiment. Its purpose is to validate the radiopurity of the scintillator to assure that all components of the JUNO scintillator system work to specifications and only neutrino-grade scintillator is filled into the JUNO Central Detector. The aspired sensitivity level of $$10^{-16}\hbox { g/g}$$ 10 - 16 g/g of $$^{238}\hbox {U}$$ 238 U and $$^{232}\hbox {Th}$$ 232 Th requires a large ( $$\sim 20\,\hbox {m}^3$$ ∼ 20 m 3 ) detection volume and ultralow background levels. The present paper reports on the design and major components of the OSIRIS detector, the detector simulation as well as the measuring strategies foreseen and the sensitivity levels to U/Th that can be reached in this setup.

Abstract JUNO is a massive liquid scintillator detector with a primary scientific goal of determining the neutrino mass ordering by studying the oscillated anti-neutrino flux coming from two nuclear power plants at 53 km distance. The expected signal anti-neutrino interaction rate is only 60 counts per day (cpd), therefore a careful control of the background sources due to radioactivity is critical. In particular, natural radioactivity present in all materials and in the environment represents a serious issue that could impair the sensitivity of the experiment if appropriate countermeasures were not foreseen. In this paper we discuss the background reduction strategies undertaken by the JUNO collaboration to reduce at minimum the impact of natural radioactivity. We describe our efforts for an optimized experimental design, a careful material screening and accurate detector production handling, and a constant control of the expected results through a meticulous Monte Carlo simulation program. We show that all these actions should allow us to keep the background count rate safely below the target value of 10 Hz (i.e. ∼1 cpd accidental background) in the default fiducial volume, above an energy threshold of 0.7 MeV.

Abstract Atmospheric neutrinos are one of the most relevant natural neutrino sources that can be exploited to infer properties about cosmic rays and neutrino oscillations. The Jiangmen Underground Neutrino Observatory (JUNO) experiment, a 20 kton liquid scintillator detector with excellent energy resolution is currently under construction in China. JUNO will be able to detect several atmospheric neutrinos per day given the large volume. A study on the JUNO detection and reconstruction capabilities of atmospheric $$\nu _e$$ ν e and $$\nu _\mu $$ ν μ fluxes is presented in this paper. In this study, a sample of atmospheric neutrino Monte Carlo events has been generated, starting from theoretical models, and then processed by the detector simulation. The excellent timing resolution of the 3” PMT light detection system of JUNO detector and the much higher light yield for scintillation over Cherenkov allow to measure the time structure of the scintillation light with very high precision. Since $$\nu _e$$ ν e and $$\nu _\mu $$ ν μ interactions produce a slightly different light pattern, the different time evolution of light allows to discriminate the flavor of primary neutrinos. A probabilistic unfolding method has been used, in order to infer the primary neutrino energy spectrum from the detector experimental observables. The simulated spectrum has been reconstructed between 100 MeV and 10 GeV, showing a great potential of the detector in the atmospheric low energy region.

Objectives This study investigates the relationship between socioeconomic environment (SEE) and survival after ST-segment elevation myocardial infarction (STEMI) separately for women and men in the City of Vienna, Austria.Design Hospital-based observational data of STEMI patients are linked with district-level information on SEE and the mortality register, enabling survival analyses with a 19-year follow-up (2000–2018).Setting The analysis is set at the main tertiary care hospital of the City of Vienna. On weekends, it is the only hospital in charge of treating STEMIs and thus provides representative data for the Viennese population.Participants The study comprises a total of 1481 patients with STEMI, including women and men aged 24–94 years.Primary and secondary outcome measures Primary outcome measures are age at STEMI and age at death. We further distinguish between deaths from coronary artery disease (CAD), deaths from acute coronary syndrome (ACS), and other causes of death. SEE is proxied via mean individual gross income from employment in each municipal district.Results Results are based on Kaplan-Meier survival probability estimates, Cox proportional hazard regressions and competing risk models, always using age as the time scale. Descriptive findings suggest a socioeconomic gradient in the age at death after STEMI. This finding is, however, not supported by the regression results. Female patients with STEMI have better survival outcomes, but only for deaths related to CAD (HR: 0.668, 95% CIs 0.452 to 0.985) and other causes of deaths (HR: 0.627, 95% CIs 0.444 to 0.884), and not for deaths from the more acute ACS.Conclusions Additional research is necessary to further disentangle the interaction between SEE and age at STEMI, as our findings suggest that individuals from poorer districts have STEMI at younger ages, which indicates vulnerability in regard to health conditions in these neighbourhoods.

Abstract We present the calibration strategy for the 20 kton liquid scintillator central detector of the Jiangmen Underground Neutrino Observatory (JUNO). By utilizing a comprehensive multiple-source and multiple-positional calibration program, in combination with a novel dual calorimetry technique exploiting two independent photosensors and readout systems, we demonstrate that the JUNO central detector can achieve a better than 1% energy linearity and a 3% effective energy resolution, required by the neutrino mass ordering determination.

The genetic testing of hereditary ataxias includes screening for CAG-repeat expansions as well as pathogenic variants and nontranslated oligonucleotide expansion, which can cause spinocerebellar ataxia (SCA). Genotype-phenotype correlations of several SCA subtypes are difficult to establish, and the underlying mechanisms remain unclear. Here, we report a 58-year-old male patient who presented with severe generalized ataxia, horizontal gaze-evoked nystagmus, cognitive impairment and a positive family history of gait difficulties. Genetic panel diagnostics revealed a new nonsense pathogenic variant in the CACNA1A gene (c.2983G>T; p. Glu995*) that segregated with the phenotype in three clinically affected family members. This gene is related to SCA type 6 (SCA6), episodic ataxia type 2, familial hemiplegic migraine type 1, among others. When it is supported by the clinical findings and family history, additional DNA sequencing beyond fragment length analysis should be performed.

Abstract As advanced heart failure (HF) with elevated NT-proBNP is characterized by an activated coagulation system, coronary events clinically noticed as sudden or HF death may be more common after treatment with first- compared to newer-generation DES. Our study evaluates (1) if patients with left ventricular dysfunction (LVSD) who underwent percutaneous coronary intervention have a better survival with first- or newer-generation DES, and (2) if the survival benefit is predicted by NT-proBNP. Our observational study evaluated patients with LVSD who were registered in the coronary catheter laboratory database of the Medical University of Vienna. Multivariate Cox regression analyses tested an interaction in the risk of death between those with lower or elevated NT-proBNP levels and the stent-generation. The relative risk of newer- compared to first-generation DES as reference was calculated for patients with low and elevated NT-proBNP levels. In 340 patients (178 newer- and 162 first-generation DES) stent-generation and NT-proBNP were independent predictors of death. When the stent-generation*NTproBNP interaction was forced into a Cox regression model, this term independently predicted death. The relative risk of first- compared to newer-generation DES was similar in patients with lower NT-proBNP (HR 1.02, 95% CI 0.95–1.10, p = 0.560), but was higher in patients with elevated NT-proBNP (HR 1.06, 95% CI 1.01–1.10, p = 0.020). Death is associated to stent-generation. NT-proBNP is a predictor for the stent generation used: elevated levels demonstrated a higher mortality risk when using first- compared to newer-generation DES, while lower levels showed a similar risk when using either DES-generation.

PurposeDiffusion-weighted imaging (DWI) is an essential element of almost every brain MRI examination. The most widely applied DWI technique, a single-shot echo-planar imaging DWI (EPI-DWI) sequence, suffers from a high sensitivity to magnetic field inhomogeneities. As an alternative, a single-shot stimulated echo acquisition mode diffusion-weighted MRI (STEAM-DWI) has recently been re-introduced after it became significantly faster. The aim of the study was to investigate the applicability of STEAM-DWI as a substitute to EPI-DWI in a daily routine of pediatric radiology.MethodsRetrospectively, brain MRI examinations of 208 children with both EPI-DWI and STEAM-DWI were assessed. Visual resolution and diagnostic confidence were evaluated, the extent of susceptibility artifacts was quantified, and contrast-to-noise ratio was calculated in case of diffusion restriction. Furthermore, the correlation of apparent diffusion coefficient values between STEAM-DWI and EPI-DWI was tested.ResultsSTEAM-DWI was inferior to EPI-DWI in visual resolution but with higher diagnostic confidence and lower artifact size. The apparent diffusion coefficient values of both sequences demonstrated excellent correlation. The contrast-to-noise ratio of STEAM-DWI was only half of that of EPI-DWI (58% resp. 112%).ConclusionSTEAM-DWI is a robust alternative to EPI-DWI when increased susceptibility artifacts are to be expected. Drawbacks are a lower contrast-to-noise ratio and poorer visual resolution.

Thecomas are rare benign sex cord-stromal tumors that account for less than 1% of all ovarian tumors. They usually affect postmenopausal women and become symptomatic with abnormal bleeding. In adolescents, less than 10 cases have been reported so far, mainly with symptoms of hormonal disbalance. Extraovarian thecomas represent an even rarer entity, with only two cases described so far, none of them in the pediatric population. We report the case of a 14-year-old girl who presented with sudden-onset abdominal pain, dysuria, and fever, as well as highly elevated serum inflammation parameters. Ultrasound and magnetic resonance imaging (MRI) revealed a large, inhomogeneous pelvic mass (16 cm × 9 cm × 13 cm) with indistinct margins, suggestive of an infiltrative malignant teratoma or sarcoma. Laparoscopy confirmed a large mass of unknown origin. In contrast to the infiltrative character seen on preoperative MRI, the tumor could be easily exteriorized and resected after conversion to laparotomy. Ovaries, fallopian tubes, and uterus remained unaffected. Histopathology revealed a benign nonluteinized thecoma. The postoperative course and 19-month follow-up were uneventful.

Radiation-Induced Cavernous Hemangioma (RICH) is a possible consequence of brain irradiation that rarely causes symptoms but can result in severe hemorrhage and neurological symptoms. To date, only small numbers of RICH cases have been reported in the literature. We report on a case of a 16-year old male who underwent surgery for RICH due to intralesional hemorrhage. Follow-up imaging showed increasing hemorrhage of one of the lesions over time since irradiation. Additionally, the patient experienced headache and seizure-like events. Therefore, microsurgical resection was performed to prevent further hemorrhage and the risk of a symptomatic bleeding event. Imaging carried out after surgery showed no sign of any new hemorrhage but still multiple other RICH lesions.Patients with RICH are often asymptomatic, but still it can lead to severe hemorrhage. Thus, follow-up imaging after brain irradiation is crucial to detect early signs of RICH and assess its evolution. To prevent symptomatic hemorrhage, surgery for RICH should be carefully considered on a case-by-case basis if the patient becomes symptomatic or if imaging shows increasing hemorrhage.

Background: In the past few years, several randomized trials have clearly shown that endovascular treatment (ET) in addition to intravenous thrombolysis (IVT) is superior to IVT alone in patients with proximal cerebral arterial occlusions. However, the effectiveness of ET in pre-stroke dependent patients (modified Rankin Scale ≥3) is uncertain.Methods: Using our prospectively obtained stroke database, we analyzed the impact of pre-stroke dependence on the rates of poor outcome (discharge mRS 5–6), in-hospital death, infarct sizes, and symptomatic intracranial hemorrhage (SICH) in patients with distal intracranial carotid artery M1 and M2 occlusions during two time periods.Results: From 1/2008 to 10/2012, a total of 544 patients (455 without and 89 with dependence) were treated with IVT, and from 11/2012 to 12/2019 a total of 1,061 patients (919 without and 142 with dependence) received ET (with or without IVT). Irrespective of the treatment modality, the dependent patients had significantly higher rates of poor outcome (55 vs. 32%, p < 0.001), death (24 vs. 11%; p < 0.001), or SICH (8.2 vs. 3.6%, p < 0.01) than independent patients. In dependent patients, ET significantly reduced the rates of poor outcome (49 vs. 64%, p < 0.01) and led to smaller infarcts, whereas the rates of in-hospital death (25 vs. 22%; p = 0.6) or SICH (8.5 vs. 7.9%, p = 0.9) were comparable between both treatment modalities.Conclusions: Compared with IVT, ET avoids poor outcome and leads to smaller infarcts in dependent patients. However, the overall high rates of poor outcome in this patient population stress the importance to perform decisions based on a case-by-case basis.

Background: It is often advised to ensure a high-protein intake during energy-restricted diets. However, it is unclear whether a high-protein intake is able to maintain muscle mass and contractility in the absence of resistance training.Materials and Methods: After 1 week of body mass maintenance (45 kcal/kg), 28 male college students not performing resistance training were randomized to either the energy-restricted (ER, 30 kcal/kg, n = 14) or the eucaloric control group (CG, 45 kcal/kg, n = 14) for 6 weeks. Both groups had their protein intake matched at 2.8 g/kg fat-free-mass and continued their habitual training throughout the study. Body composition was assessed weekly using multifrequency bioelectrical impedance analysis. Contractile properties of the m. rectus femoris were examined with Tensiomyography and MyotonPRO at weeks 1, 3, and 5 along with sleep (PSQI) and mood (POMS).Results: The ER group revealed greater reductions in body mass (Δ −3.22 kg vs. Δ 1.90 kg, p < 0.001, partial η2 = 0.360), lean body mass (Δ −1.49 kg vs. Δ 0.68 kg, p < 0.001, partial η2 = 0.152), body cell mass (Δ −0.85 kg vs. Δ 0.59 kg, p < 0.001, partial η2 = 0.181), intracellular water (Δ −0.58 l vs. Δ 0.55 l, p < 0.001, partial η2 = 0.445) and body fat percentage (Δ −1.74% vs. Δ 1.22%, p < 0.001, partial η2 = 433) compared to the CG. Contractile properties, sleep onset, sleep duration as well as depression, fatigue and hostility did not change (p > 0.05). The PSQI score (Δ −1.43 vs. Δ −0.64, p = 0.006, partial η2 = 0.176) and vigor (Δ −2.79 vs. Δ −4.71, p = 0.040, partial η2 = 0.116) decreased significantly in the ER group and the CG, respectively.Discussion: The present data show that a high-protein intake alone was not able to prevent lean mass loss associated with a 6-week moderate energy restriction in college students. Notably, it is unknown whether protein intake at 2.8 g/kg fat-free-mass prevented larger decreases in lean body mass. Muscle contractility was not negatively altered by this form of energy restriction. Sleep quality improved in both groups. Whether these advantages are due to the high-protein intake cannot be clarified and warrants further study. Although vigor was negatively affected in both groups, other mood parameters did not change.

Abstract Background According to the World Health Organization, coronary artery disease (CAD), including ST-segment elevation myocardial infarction (STEMI), is the most common cause of death worldwide as well as in Europe and Austria. There is valid data on the impact of conventional risk factors on the medical outcomes for STEMI patients. However, only few studies examine the role of the socio-economic environment for medical outcomes. The main task of this study is to investigate if the socio-economic environment of patients who underwent percutaneous coronary intervention (PCI) after STEMI has an impact on the distribution of risk factors and medical outcomes. Methods The study focuses on the population of the City of Vienna, Austria, and includes 870 STEMI patients, who underwent PCI at the General Hospital of Vienna (AKH Wien) between 2008 and 2012. The following data were collected: conventional risk factors (hypertension, hyperlipidemia, diabetes, overweight, smoking, family history and vascular disease) and socio-economic indicators of the patient’s residential district (number of residents, income pre-tax, residents per general practitioner, residents per internal specialist, compulsory education only, academic degree and rate of unemployment). Cox regressions were performed to evaluate the impact of socio-economic environment and conventional risk factors on survival. Results Most of the conventional risk factors show a significant difference between deceased and surviving patients. The study revealed significant differences across districts in relation to the socio-economic background of STEMI patients. Surprisingly, medical outcomes, as measured by the survival of patients, are significantly related to a patient’s district of residence (p-Value = 0.028) but not in a systematic way as far as the socio-economic environment of these districts is concerned. Conclusions The study provides intuitive evidence for a hitherto understudied Central European context on the link between socio-economic environment and conventional risk factors at population level and the link between conventional risk factors and survival both at the population at the individual level. While this is in line with previous evidence and suggestive of the incorporation of measures of socio-economic status (SES) into policy & guidelines toward the management of CAD, more data on the SES – STEMI nexus are needed at individual level.

Abstract Background At present, the flexible endoscopic evaluation of swallowing (FEES) is one of the most commonly used methods for the objective assessment of swallowing. This multicenter trial prospectively collected data on the safety of FEES and also assessed the impact of this procedure on clinical dysphagia management. Methods Patients were recruited in 23 hospitals in Germany and Switzerland from September 2014 to May 2017. Patient characteristics, professional affiliation of the FEES examiners (physicians or speech and language therapists), side-effects and cardiorespiratory parameters, severity of dysphagia and clinical consequences of FEES were documented. Results 2401 patients, mean age 69.8 (14.6) years, 42.3% women, were included in the FEES-registry. The most common main diagnosis was stroke (61%), followed by Parkinson’s disease (6.5%). FEES was well tolerated by patients. Complications were reported in 2% of examinations, were all self-limited and resolved without sequelae and showed no correlation to the endoscopist’s previous experience. In more than 50% of investigations FEES led to changes of feeding strategies, in the majority of cases an upgrade of oral diet was possible. Discussion This study confirmed that FEES, even when performed by less experienced clinicians is a safe and well tolerated procedure and significantly impacts on the patients’ clinical course. Implementation of a FEES-service in different clinical settings may improve dysphagia care. Trial registration ClinicalTrials.gov NCT03037762, registered January 31st 2017.

Previous case series have described the safety and efficacy of different stent models for stent-assisted aneurysm coiling (SAC), but comparative analyses of procedural results are limited. This study investigates the procedural outcome and safety of three different stent models (Atlas™, LEO+™ (Baby) and Enterprise™) in the setting of elective SAC treated at a tertiary neuro-endovascular center. We retrospectively reviewed all consecutively treated patients that received endovascular SAC for intracranial aneurysms between 1 July 2013 and 31 March 2020, excluding all emergency angiographies for acute subarachnoid hemorrhage. The primary procedural outcome was the occlusion rate evaluated with the Raymond–Roy occlusion classification (RROC) assessed on digital subtraction angiography (DSA) at 6- and 12-month follow-up. Safety assessment included periprocedural adverse events (i.e., symptomatic ischemic complications, symptomatic intracerebral hemorrhage, iatrogenic perforation, dissection, or aneurysm rupture and in-stent thrombosis) and in-house mortality. Uni- and multivariable logistic regression analyses were performed to identify patient baseline and aneurysm characteristics that were associated with complete aneurysm obliteration at follow-up. A total of 156 patients undergoing endovascular treatment via SAC met the inclusion criteria. The median age was 62 years (IQR, 55–71), and 73.7% (115) of patients were female. At first follow-up (6-month) and last available follow-up (12 and 18 months), complete aneurysm occlusion was observed in 78.3% (90) and 76.9% (102) of patients, respectively. There were no differences regarding the occlusion rates stratified by stent model. Multivariable logistic analysis revealed increasing dome/neck ratio (adjusted odds ratio (aOR), 0.26.; 95% CI, 0.11–0.64; p = 0.003), increasing neck size (aOR, 0.70; 95% CI, 0.51–0.96; p = 0.027), and female sex (aOR, 4.37; 95% CI, 1.68–11.36; p = 0.002) as independently associated with treatment success. This study showed comparable rates of complete long-term aneurysm obliteration and safety following SAC for intracranial aneurysm with three different stent-models highlighting the procedural feasibility of this treatment strategy with currently available stent-models. Increased neck size and a higher dome/neck ratio were independent variables associated with less frequent complete aneurysm obliteration.

Introduction: The purpose of this study was to clarify whether blood-flow restriction during resting intervals [resting blood-flow restriction (rBFR)] is comparable to a continuous BFR (cBFR) training regarding its effects on maximum strength, hypertrophy, fatigue resistance, and perceived discomfort.Materials and Methods: Nineteen recreationally trained participants performed four sets (30-15-15-15 repetitions) with 20% 1RM on a 45° leg press twice a week for 6 weeks (cBFR, n = 10; rBFR, n = 9). Maximum strength, fatigue resistance, muscle thickness, and girth were assessed at three timepoints (pre, mid, and post). Subjective pain and perceived exertion were determined immediately after training at two timepoints (mid and post).Results: Maximum strength (p < 0.001), fatigue resistance (p < 0.001), muscle thickness (p < 0.001), and girth (p = 0.008) increased in both groups over time with no differences between groups (p > 0.05). During the intervention, the rBFR group exposed significantly lower perceived pain and exertion values compared to cBFR (p < 0.05).Discussion: Resting blood-flow restriction training led to similar gains in strength, fatigue resistance, and muscle hypertrophy as cBFR training while provoking less discomfort and perceived exertion in participants. In summary, rBFR training could provide a meaningful alternative to cBFR as this study showed similar functional and structural changes as well as less discomfort.

While endovascular treatment (ET) improves clinical outcomes in patients with proximal vessel occlusions compared to thrombolysis (IVT), the impact of ET on the frequency of stroke-associated pneumonia (SAP) is uncertain. We compared the rates of SAP in patients with large vessel occlusions in the anterior circulation after IVT or ET. We also determined risk factors for SAP, as well as the impact of SAP on early clinical outcomes. A total of 544 patients were treated with IVT, and 1061 patients received ET (with or without IVT). The rates of SAP did not differ significantly between ET (217/1061; 20%) and IVT (100/544; 18%) (p = 0.3). Overall, the occurrence of SAP was significantly associated with mortality and a poor clinical outcome. In the multivariable regression analysis, age, sex, the presence of dysphagia, early signs of ischemia on imaging and a history of stroke and mechanical ventilation were all significantly associated with the occurrence of SAP. In patients with large vessel occlusions, the introduction of ET did not result in lower rates of SAP compared with IVT. There is an ongoing need to reduce the rates of SAP in this patient population, for which the risk factors found here could become useful.

Background Patients aged ≥90 were excluded or under‐represented in past thrombectomy trials; thus, uncertainty remains whether treatment benefits can be expected regardless of age. This study investigates outcome and safety of thrombectomy in nonagenarians to improve decision making in a real‐world setting. Methods and Results All currently available data of patients aged ≥90 enrolled in the GSR‐ET (German Stroke Registry–Endovascular Treatment) were combined with a smaller cohort from 3 tertiary stroke centers. Baseline characteristics, procedural (Thrombolysis in Cerebral Infarction scale) and functional outcomes (modified Rankin Scale; mRS), as well as complications (symptomatic intracranial hemorrhage, serious adverse events; SAEs) were analyzed. Good functional outcome was defined as mRS ≤3 at 90‐days. 203 patients with anterior circulation stroke and prestroke mRS ≤3 were included. The rate of successful recanalization (Thrombolysis in Cerebral Infarction scale ≥2b) was 75.9% (154/203). Good functional outcome (mRS ≤3) was observed in 21.6% (41 of 193) at 90‐days. In‐hospital mortality was 27.1% (55 of 203) and increased significantly at 90 days to 48.9% (93 of 190; P

BACKGROUND:Lipoprotein(a) [Lp(a)] is associated with coronary artery disease in population studies, however studies on its predictive value in patients with cardiovascular disease, in particular after acute coronary syndromes (ACS), are conflicting. The aim of this study was to investigate whether Lp(a) is associated with survival after ACS. METHODS AND RESULTS:We analyzed Lp(a) measurement in 1,245 patients who underwent coronary angiography for ACS. The median follow-up for cardiovascular and all-cause mortality was 5.0 (IQR 3.2-8.0) years. 655 (52.6%) presented with ST-segment elevation myocardial infarction (STEMI), 424 (34.1%) with Non-ST-segment elevation myocardial infarction (NSTEMI) and 166 (13.3%) underwent coronary angiography for unstable angina. Cardiovascular mortality was 9.1% and all-cause mortality was 15.7%. Patients were stratified into four groups to their Lp(a) levels. (≤15mg/dL, >15-30mg/dL, >30-60mg/dL, and >60mg/dL). Multivessel disease was significantly more common in patients with Lp(a)>60mg/dL (p

In recent years, game narrative has emerged as an area for novel game concepts and as a strategy to distinguish a particular title. However, innovation in this area comes primarily from indie companies and individual efforts by noted designers. There is a lack of trained specialists ready to produce interactive narrative experiences. Many existing practitioners are self-trained and often rely on intuition in their design practice. A key element missing from the effort towards a more sustained development and improved professional training is a set of design conventions that fulfill a role comparable to cinematic conventions like continuity editing or montage. Therefore, our research focuses on identifying, verifying and collecting such design strategies. We describe an empirical method to verify candidate design conventions through the evaluation of user reaction to A/B prototypes, which improves upon the trial-and-error process of old.

Traditionally, surgical clipping was the only available treatment modality for intracranial aneurysms. However, in the last few decades, the endovascular therapy of intracranial aneurysms (IAs) has seen a tremendous evolution and development. From coiling to flow diversion and flow disruptor devices, endovascular treatment modalities have increased in number and received broader indications throughout the years. In this review article, the treatment modalities for the endovascular management of IAs are presented, emphasizing newer devices and technologies.

RNA degradation pathways enable RNA processing, the regulation of RNA levels, and the surveillance of aberrant or poorly functional RNAs in cells. Here we provide transcriptome-wide RNA-binding profiles of 30 general RNA degradation factors in the yeast Saccharomyces cerevisiae. The profiles reveal the distribution of degradation factors between different RNA classes. They are consistent with the canonical degradation pathway for closed-loop forming mRNAs after deadenylation. Modeling based on mRNA half-lives suggests that most degradation factors bind intact mRNAs, whereas decapping factors are recruited only for mRNA degradation, consistent with decapping being a rate-limiting step. Decapping factors preferentially bind mRNAs with non-optimal codons, consistent with rapid degradation of inefficiently translated mRNAs. Global analysis suggests that the nuclear surveillance machinery, including the complexes Nrd1/Nab3 and TRAMP4, targets aberrant nuclear RNAs and processes snoRNAs.

Amylases are probably the best studied glycoside hydrolases and have a huge biotechnological value for industrial processes on starch. Multiple amylases from fungi and microbes are currently in use. Whereas bacterial amylases are well suited for many industrial processes due to their high stability, fungal amylases are recognized as safe and are preferred in the food industry, although they lack the pH tolerance and stability of their bacterial counterparts. Here, we describe three amylases, two of which have a broad pH spectrum extending to pH 8 and higher stability well suited for a broad set of industrial applications. These enzymes have the characteristic GH13 α-amylase fold with a central (β/α)8-domain, an insertion domain with the canonical calcium binding site and a C-terminal β-sandwich domain. The active site was identified based on the binding of the inhibitor acarbose in form of a transglycosylation product, in the amylases from Thamnidium elegans and Cordyceps farinosa. The three amylases have shortened loops flanking the nonreducing end of the substrate binding cleft, creating a more open crevice. Moreover, a potential novel binding site in the C-terminal domain of the Cordyceps enzyme was identified, which might be part of a starch interaction site. In addition, Cordyceps farinosa amylase presented a successful example of using the microseed matrix screening technique to significantly speed-up crystallization.

Most of the scientific literature on computer games aimed at offering or aiding in psychotherapy provides little information on the relationship between the game’s design and the player’s cognitive processes. This article investigates the use of Bloom’s taxonomy in describing a psychotherapeutic game in terms of knowledge level and cognitive processing. It introduces the Revised Bloom Taxonomy and applies this to five psychotherapeutic games (Personal Investigator, Treasure Hunt, Ricky and the Spider, Moodbot, and SuperBetter) in a two-round procedure. In the first round consensus was reached on the Player Actions with Learning Objectives (PALOs) in each game. The second round sought to determine what level of knowledge and cognitive processing can be attributed to the PALOs by placing them in the taxonomy. Our low intercoder reliability in the second round indicates that Bloom’s Revised Taxonomy is not suitable to compare and contrast content between games.

Background: Reduced left ventricular function (LVF) is a predictor for stent-thrombosis. In advanced heart failure (characterized by high NT-proBNP) with an activated coagulation system, coronary events clinically perceived as sudden death or death from heart failure may be more common in patients treated by percutaneous coronary intervention (PCI) than in patients treated by coronary artery bypass grafting (CABG). Our study analyses (1) if patients with reduced LVF who require coronary revascularization will have a better survival benefit with CABG or PCI, and (2) if the survival benefit is predicted by NT-proBNP. Methods: This observational retrospective study included patients from the coronary catheter laboratory database of the Medical University of Vienna (CCLD-MUW). Multivariate Cox regression analyses were performed to test the hypothesis that there is an interaction in the risk of death between those with lower or elevated NT-proBNP levels and the revascularization procedure (PCI or CABG). The relative risk of PCI compared to CABG as reference was calculated for patients with low and elevated NT-proBNP levels. Results: In the entire study population with 398 patients (340 PCI and 58 CABG) the revascularization procedure had no predictive value. When the revascularization procedure*NTproBNP interaction was forced into the Cox regression model, this term was an independent predictor of death. The relative risk of PCI compared to CABG was similar in patients with lower NT-proBNP—1.01 (95% confidence interval (CI), 0.45−2.24), but was significantly increased in patients with elevated NT-proBNP—1.58 (95% CI, 1.07−2.33). Conclusion: Death is associated to the revascularization procedure, but only in those patients with elevated NT-proBNP levels. NT-proBNP is a predicting factor for the revascularization procedure: elevated levels showed an increased risk of death after PCI compared to CABG, whereas lower levels were associated with a similar risk after both revascularization procedures.

Age is a strong predictor of survival in patients with coronary artery disease. In elder patients with increasing co-morbidities percutaneous coronary intervention (PCI) is associated with more complications and worse outcome. The calculation of relative survival rates adjusts for the "background" mortality in the general population by correcting for age and gender. We analyzed if elder patients after elective PCI have a worse relative survival compared to younger patient groups.A total of 8,342 patients who underwent elective PCI at two high volume centers between 1998 and 2009 were analyzed.The survival of our patients after PCI (observed survival) was slightly lower compared to the general population (expected survival) resulting in a slightly decreasing relative survival curve. In a multivariate Cox regression model age amongst others was a strong predictor of survival. Stratifying patients according to their age the relative survival curves of younger patients (Quartile 1: 73 years; 2,307 patients) were similar. The relative survival of mid-aged patients (Quartile 2: 58-65 years; 1,899 patients) was better than that of all other patient groups. The profile of cardiovascular risk factors differs between the various groups resulting in different composition and burden of coronary plaques in an optical coherence tomography sub-study.Patients after elective PCI have a slightly worse long-term survival compared to the age- and sex-matched general population. This is also true for different groups of age except for mid-aged patients between 58 and 63 years. Elder patients between 66 and 73 years and above 73 years have a similar relative survival compared to younger patients below 58 years, and might therefore have similar benefit from elective PCI.

The protocol describes the generation of variants of chloromuconolactone dehalogenase from Rhodococcus opacus (R. opacus) 1CP. ClcF is a multimeric protein, which catalyses the dechlorination of 5-chloromuconolactone to cis-dienelactone in the 3-chlorocatecholic acid degradation pathway. The protocol describes the workflow for the purification and subsequent crystallization of the enzyme. The used workflow and the described techniques could be easily adapted to any other protein/enzyme intended to be crystallized by the potential user for subsequent structure determination. The protocol does not involve expensive specialized equipment which allows the use in standard laboratories not specially dedicated to macromolecular crystallography.

Objective. The aim of the present study was to correlate new periprocedural diffusion-weighted imaging (DWI) lesions during stenting of supra-aortal arteries with the level of platelet inhibition using point-of-care analysis. Background. Cardiological studies have shown that patients undergoing coronary PTA have a significantly elevated risk of severe thrombotic complications if patients show insufficient inhibition of platelet function. Methods. From August 2008 to June 2009, 44 patients with an indication of supra-aortal angioplasty and/or stenting were prospectively enrolled. Platelet reactivity was tested using a Multiplate device (Dynabyte). These patients underwent MRI before and after the intervention to determine the prevalence of new DWI lesions. The primary endpoint was the prevalence of DWI lesions; the secondary endpoint was clinical status until discharge from hospital. Results. There was no significant relationship between the primary endpoint and the degree of platelet function. Patients with high platelet reactivity showed the same amount of periprocedural complications as patients with sufficient inhibition of platelets. Conclusions. Clopidogrel did not have a protective effect on periprocedural complications, nor did it decrease the number of silent DWI lesions after the procedure. The predescribed strong relationship between high platelet reactivity and early post-procedural adverse events was not observed in our cohort.

Early treatment with rt-PA is critical for favorable outcome of acute stroke. However, only a very small proportion of stroke patients receive this treatment, as most arrive at hospital too late to be eligible for rt-PA therapy.We developed a "Mobile Stroke Unit", consisting of an ambulance equipped with computed tomography, a point-of-care laboratory system for complete stroke laboratory work-up, and telemedicine capabilities for contact with hospital experts, to achieve delivery of etiology-specific and guideline-adherent stroke treatment at the site of the emergency, well before arrival at the hospital. In a departure from current practice, stroke patients could be differentially treated according to their ischemic or hemorrhagic etiology even in the prehospital phase of stroke management. Immediate diagnosis of cerebral ischemia and exclusion of thrombolysis contraindications enabled us to perform prehospital rt-PA thrombolysis as bridging to later intra-arterial recanalization in one patient. In a complementary patient with cerebral hemorrhage, prehospital diagnosis allowed immediate initiation of hemorrhage-specific blood pressure management and telemedicine consultation regarding surgery. Call-to-therapy-decision times were 35 minutes.This preliminary study proves the feasibility of guideline-adherent, etiology-specific and causal treatment of acute stroke directly at the emergency site.

Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD.Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals.Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13-0.24] mmol/L, p = 1.5x10(-10)). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7)). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD.A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD.