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Introduction: Misfolding of amyloidogenic proteins is a molecular hallmark of neurodegenerative diseases in humans. A detailed understanding of the underlying molecular mechanisms is mandatory for developing innovative therapeutic approaches. The bovine PI3K-SH3 domain has been a model system for aggregation and fibril formation. Methods: We monitored the fibril formation kinetics of low pH-denatured recombinantly expressed [U- 13 C, 15 N] labeled bovine PI3K-SH3 by a combination of solution NMR, high-resolution magic angle spinning (HR-MAS) NMR and solid-state NMR spectra. Solution NMR offers the highest sensitivity and, therefore, allows for the recording of two-dimensional NMR spectra with residue-specific resolution for individual time points of the time series. However, it can only follow the decay of the aggregating monomeric species. In solution NMR, aggregation occurs under quiescent experimental conditions. Solid-state NMR has lower sensitivity and allows only for the recording of one-dimensional spectra during the time series. Conversely, solid-state NMR is the only technique to detect disappearing monomers and aggregated species in the same sample by alternatingly recoding scalar coupling and dipolar coupling (CP)-based spectra. HR-MAS NMR is used here as a hybrid method bridging solution and solid-state NMR. In solid-state NMR and HR-MAS NMR the sample is agitated due to magic angle spinning. Results: Good agreement of the decay rate constants of monomeric SH3, measured by the three different NMR methods, is observed. Moderate MAS up to 8 kHz seems to influence the aggregation kinetics of seeded fibril formation only slightly. Therefore, under sufficient seeding (1% seeds used here), quiescent conditions (solution NMR), and agitated conditions deliver similar results, arguing against primary nucleation induced by MAS as a major contributor. Using solid-state NMR, we find that the amount of disappeared monomer corresponds approximately to the amount of aggregated species under the applied experimental conditions (250 µM PI3K-SH3, pH 2.5, 298 K, 1% seeds) and within the experimental error range. Data can be fitted by simple mono-exponential conversion kinetics, with lifetimes τ in the 14-38 h range. Atomic force microscopy confirms that fibrils substantially grew in length during the aggregation experiment. This argues for fibril elongation as the dominant growth mechanism in fibril mass (followed by the CP-based solid-state NMR signal). Conclusion: We suggest a combined approach employing both solution NMR and solid-state NMR, back-to-back, on two aliquots of the same sample under seeding conditions as an additional approach to follow monomer depletion and growth of fibril mass simultaneously. Atomic force microscopy images confirm fibril elongation as a major contributor to the increase in fibril mass., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gardon, Becker, Rähse, Hölbling, Apostolidis, Schulz, Bochinsky, Gremer, Heise and Lakomek.)

Background: Over the past decades, assisted reproductive technologies (ART) have gained remarkable influence in the treatment of infertility and account for more than 2 % of births in European countries nowadays. Accumulating evidence suggests ART to cause cardiovascular alterations, including left ventricular (LV) dysfunctions, within its offspring. The aim of this study was to assess LV systolic function in subjects conceived through ART in comparison to spontaneously conceived peers., Methods: For the assessment of LV morphology and LV function, M-Mode echocardiography, pulsed wave Doppler and two-dimensional speckle tracking echocardiography (2DSTE) were applied. LV ejection fraction (EF) and fractional shortening (FS) were assessed in M-Mode and calculated by Teichholz formula. EF was additionally assessed semiautomatically through 2DSTE., Results: In total, 64 ART subjects and 83 spontaneously conceived controls with no significant differences in age (12.52 ± 5.64 years vs. 13.20 ± 5.95 years, p  = 0.486) and sex were included in the analysis. In the ART cohort, significantly lower values were observed for M-Mode assessed EF (63.63 ± 5.17 % vs. 65.35 ± 5.10 %, p  = 0.046) and FS (34.26 ± 3.87 % vs. 35.60 ± 3.84 %, p  = 0.038). However, after the adjustment for birth weight percentile and gestational age, M-Mode assessed EF and FS displayed no significant differences between both groups. LV morphology and remaining systolic function parameters, such as mitral annular plane systolic excursion, aortic velocity time integral, global peak longitudinal strain and 2DSTE measured EF, were comparable between both groups., Conclusion: This study suggests a lower LV systolic function in ART subjects, visualized by significantly lower values for M-Mode assessed EF and FS, compared to spontaneously conceived peers. The clinical relevance of these findings has to be investigated as the above-mentioned parameters were in normal reference range. In addition, LV systolic function parameters evaluated by other echocardiographic imaging modalities were comparable between both groups. Therefore, further studies will be required to evaluate the influence of ART on LV systolic function and cardiovascular morbidity in the future., Competing Interests: NR received support for symposium and others from Ferring Arzneimittel GmbH, Theramex Germany GmbH, Merck KGaA, Teva GmbH, Besins Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sciuk, Vilsmaier, Kramer, Langer, Kolbinger, Li, Jakob, Rogenhofer, Dalla-Pozza, Thaler, Haas and Oberhoffer.)

Purpose: To investigate the sensitivity and specificity of central retinal artery occlusion (CRAO)-Detection Score in diagnosing CRAO via questionnaire and without fundoscopy., Methods: This prospective study enrolled 176 emergency patients suffering from acute visual loss, of whom 38 were suffering from CRAO. Before conducting any examination, we administered our questionnaire containing six questions, followed by a thorough ophthalmologic examination to make the diagnosis. Statistical analysis involved a LASSO penalised multivariate logistic regression model., Results: Our receiver operating characteristic (ROC) analysis based on a LASSO penalised multivariate logistic regression model showed an area under the curve (AUC) of 0.9 - three out of six questions were selected by LASSO. Interestingly, the unweighted ROC analysis of only two questions (Short CRAO-Detection Score) yielded similar results with an AUC of 0.88. The short CRAO-Detection Score of 2 yielded 14% (4/28) false positive patients., Conclusion: This prospective study demonstrates that a high percentage of CRAO patients are detectable with a questionnaire. The CRAO-Detection Score might be used to triage patients suffering acute visual loss, which is important as intravenous fibrinolysis seem to be time-dependent to be effective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Casagrande, Steinhorst, Dippel, Kück, Grohmann, Spitzer, Poli, Feltgen and Schultheiss.)

Background: The consumption of Energy Drinks (ED) is very popular among children and teenagers. While potential cardiovascular side effects of these beverages are suggested, the acute impact of ED consumption on the pediatric cardiovascular system has not been systematically examined yet. The aim of this study was to investigate the acute effects of ED consumption on blood pressure and heart rate in healthy children and teenagers., Methods: This study was a randomized, single-blind, placebo-controlled, crossover clinical trial. On two consecutive days, the study participants were asked to consume a weight-adjusted amount of an ED (3 mg caffeine per kg of body weight) or a placebo containing a similar amount of sugar but without conventional ED ingredients. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were measured at the following time points: baseline as well as 30, 60, 120 and 240 min after beverage consumption., Results: In total, 27 healthy children and adolescents (mean age 14.53 ± 2.40 years, 14 male) were included in the present study. Compared to placebo intake, mean SBP was demonstrated to be up to 5.23 mmHg ( p < 0.0001) and mean DBP up to 3.29 mmHg ( p < 0.001) increased after ED consumption. Prevalence of elevated blood pressure, stage 1 and stage 2 hypertension was higher after ED consumption. Heart rate tended to be lower after ED consumption., Conclusions: The acute ED consumption is associated with a significantly increased SBP and DBP in healthy children and teenagers. Minors, particularly those with pre-existing health conditions, should be discouraged from drinking EDs., Clinical Trial Registration: https://www.drks.de/drks&#95;web/, identifier: DRKS00027580., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oberhoffer, Li, Jakob, Dalla-Pozza, Haas and Mandilaras.)

Introduction: Postoperative nausea and vomiting (PONV) is among the most common distressing complications of surgery under anesthesia. Previous studies have demonstrated that patients who undergo craniotomy have incidences of nausea and vomiting as high as 50-70%. The main purpose of this pilot study is to assess the incidence of PONV by using two different prophylactic regimens in subjects undergoing a craniotomy. Thus, we designed this study to assess the efficacy and safety of triple therapy with the combination of dexamethasone, promethazine, and aprepitant versus ondansetron to reduce the incidence of PONV in patients undergoing craniotomy., Materials and Methods: This is a prospective, single center, two-armed, randomized, double-dummy, double-blind, pilot study. Subjects were randomly assigned to one of the two treatment groups. Subjects received 40 mg of aprepitant pill (or matching placebo pill) 30-60 min before induction of anesthesia and 4 mg of ondansetron IV (or 2 ml of placebo saline solution) at induction of anesthesia. In addition, all subjects received 25 mg of promethazine IV and 10 mg of dexamethasone IV at induction of anesthesia. Assessments of PONV commenced for the first 24 h after surgery and were subsequently assessed for up to 5 days., Results: The overall incidence of PONV during the first 24 h after surgery was 31.0% (n = 15) in the aprepitant group and 36.2% (n = 17) for the ondansetron group. The median times to first emetic and significant nausea episodes were 7.6 (2.9, 48.7) and 14.3 (4.4, 30.7) hours, respectively, for the aprepitant group and 6.0 (2.2, 29.5) and 9.6 (0.7, 35.2) hours, respectively, for the ondansetron group. There were no statistically significant differences between these groups. No adverse events directly related to study medications were found., Conclusion: This pilot study showed similar effectiveness when comparing the two PONV prophylaxis regimens. Our data showed that both treatments could be effective regimens to prevent PONV in patients undergoing craniotomy under general anesthesia. Future trials testing new PONV prophylaxis regimens in this surgical population should be performed to gain a better understanding of how to best provide prophylactic treatment.