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The apple fruit (Malus domestica L. Borkh) is one of the most popular fruits worldwide. Beyond their beneficial properties, apples contain proteins that trigger allergic reactions in susceptible consumers. Mal d1 to d4 are allergens present in a variety of different isoforms in apples. In this study, we used proteomics to quantify all four Mal d proteins in 52 apple genotypes with varying allergenic potentials. A total of 195, 17, 14, and 18 peptides were found to be related to Mal d1, d2, d3, and d4 proteins, respectively of which 25 different Mal d proteins could be unambiguously identified. The allergenic potential of the Mal d isoforms was characterized by comparing the isoform abundance with the allergenic score of genotypes from oral challenge tests. The detected Mal d peptides presumably have different IgE binding properties and could be used as potential molecular markers to discriminate between hypoallergenic and hyperallergenic cultivars.
Currently, only non-imaging chlorophyll fluorescence measurements are used to identify the Lower Oxygen Limit (LOL) in Dynamic Controlled Atmosphere - Chlorophyll Fluorescence (DCA-CF) storage. The disadvantage of non-imaging fluorescence is that no statement can be made about the spatial heterogeneity of the sample. In contrast, chlorophyll fluorescence imaging can detect spatial heterogeneity of photosynthetic activity and has been established in research for some decades because the information benefit is higher. In this study, the chlorophyll fluorescence (Fo, Fm, Fv, Fv/Fm) of apples (Malus x domestica, BORKH.) was measured with a fluorescence imaging system in situ during storage. Intact apples of ‘Braeburn’ and ‘Golden Delicious’ were stored under low-oxygen stress conditions (< 1 kPa). The metabolic shift from aerobic to fermentative metabolism was made visible with the chlorophyll fluorescence imaging and was spatially localized on the sample. Furthermore, a method was developed to identify the LOL based on the chlorophyll fluorescence imaging combined with the histogram division method. This method considers the heterogeneity of the fluorescence and bundles the measured Fo data as histograms. Our results showed that the fluorescence imaging combined with the histogram division method can be a powerful tool for identifying the LOL.
Objectives: To measure and assess the economic impact of adherence to a single quality indicator (QI) regarding weaning from invasive ventilation.
Design: Retrospective observational single-centre study, based on electronic medical and administrative records.
Setting: Intensive care unit (ICU) of a German university hospital, reference centre for acute respiratory distress syndrome.
Participants: Records of 3063 consecutive mechanically ventilated patients admitted to the ICU between 2012 and 2017 were extracted, of whom 583 were eligible adults for further analysis. Patients’ weaning protocols were evaluated for daily adherence to quality standards until ICU discharge. Patients with <65% compliance were assigned to the low adherence group (LAG), patients with ≥65% to the high adherence group (HAG).
Primary and secondary outcome measures: Economic healthcare costs, clinical outcomes and patients’ characteristics.
Results: The LAG consisted of 378 patients with a median negative economic results of −€3969, HAG of 205 (−€1030), respectively (p<0.001). Median duration of ventilation was 476 (248; 769) hours in the LAG and 389 (247; 608) hours in the HAG (p<0.001). Length of stay (LOS) in the LAG on ICU was 21 (12; 35) days and 16 (11; 25) days in the HAG (p<0.001). LOS in the hospital was 36 (22; 61) days in the LAG, and within the HAG, respectively, 26 (18; 48) days (p=0.001).
Conclusions: High adherence to this single QI is associated with better clinical outcome and improved economic returns. Therefore, the results support the adherence to QI. However, the examined QI does not influence economic outcome as the decisive factor.
During gestation, the most drastic change in oxygen supply occurs with the onset of ventilation after birth. As the too early exposure of premature infants to high arterial oxygen pressure leads to characteristic diseases, we studied the adaptation of the oxygen sensing system and its targets, the hypoxia-inducible factor- (HIF-) regulated genes (HRGs) in the developing lung. We draw a detailed picture of the oxygen sensing system by integrating information from qPCR, immunoblotting, in situ hybridization, and single-cell RNA sequencing data in ex vivo and in vivo models. HIF1α protein was completely destabilized with the onset of pulmonary ventilation, but did not coincide with expression changes in bona fide HRGs. We observed a modified composition of the HIF-PHD system from intrauterine to neonatal phases: Phd3 was significantly decreased, while Hif2a showed a strong increase and the Hif3a isoform Ipas exclusively peaked at P0. Colocalization studies point to the Hif1a-Phd1 axis as the main regulator of the HIF-PHD system in mouse lung development, complemented by the Hif3a-Phd3 axis during gestation. Hif3a isoform expression showed a stepwise adaptation during the periods of saccular and alveolar differentiation. With a strong hypoxic stimulus, lung ex vivo organ cultures displayed a functioning HIF system at every developmental stage. Approaches with systemic hypoxia or roxadustat treatment revealed only a limited in vivo response of HRGs. Understanding the interplay of the oxygen sensing system components during the transition from saccular to alveolar phases of lung development might help to counteract prematurity-associated diseases like bronchopulmonary dysplasia.
Background
A peripheral venous catheter (PVC) is the most widely used device for obtaining vascular access, allowing the administration of fluids and medication. Up to 25% of adult patients, and 50% of pediatric patients experience a first-attempt cannulation failure. In addition to patient and clinician characteristics, device features might affect the handling and success rates. The objective of the study was to compare the first-attempt cannulation success rate between PVCs with wings and a port access (Vasofix® Safety, B. Braun, abbreviated hereon in as VS) with those without (Introcan® Safety, B. Braun, abbreviated hereon in as IS) in an anesthesiological cohort.
Methods
An open label, multi-center, randomized trial was performed. First-attempt cannulation success rates were examined, along with relevant patient, clinician, and device characteristics with univariate and multivariate analyses. Information on handling and adherence to use instructions was gathered, and available catheters were assessed for damage.
Results
Two thousand three hundred four patients were included in the intention to treat analysis. First-attempt success rate was significantly higher with winged and ported catheters (VS) than with the non-winged, non-ported design (IS) (87.5% with VS vs. 78.2% with IS; PChi < .001). Operators rated the handling of VS as superior (rating of “good” or “very good: 86.1% VS vs. 20.8% IS, PChi < .001). Reinsertion of the needle into the catheter after partial withdrawal—prior or during the catheterization attempt—was associated with an increased risk of cannulation failure (7.909, CI 5.989–10.443, P < .001 and 23.023, CI 10.372–51.105, P < .001, respectively) and a twofold risk of catheter damage (OR 1.999, CI 1.347–2.967, P = .001).
Conclusions
First-attempt cannulation success of peripheral, ported, winged catheters was higher compared to non-ported, non-winged devices. The handling of the winged and ported design was better rated by the clinicians. Needle reinsertions are related to an increase in rates of catheter damage and cannulation failure.
Background: New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure.
Aims: The aim of this study was to identify the procedural step(s) that are associated with an increased risk of cerebral embolisation during TEER-MV with the MitraClip system. Furthermore, the risk of overt stroke and silent brain ischaemia after TEER-MV was assessed.
Methods: In this prospective, pre-specified observational study, all patients underwent continuous transcranial Doppler examination during TEER-MV to detect microembolic signals (MES). MES were assigned to specific procedural steps: (1) transseptal puncture and placement of the guide, (2) advancing and adjustment of the clip in the left atrium, (3) device interaction with the MV, and (4) removal of the clip delivery system and the guide. Neurological examination using the National Institutes of Health Stroke Scale (NIHSS) and cerebral MRI were performed before and after TEER-MV.
Results: Fifty-four patients were included. The number of MES differed significantly between the procedural steps with the highest numbers observed during device interaction with the MV. Mild neurological deterioration (NIHSS ≤3) occurred in 9/54 patients. New ischaemic lesions were detected in 21/24 patients who underwent MRI. Larger infarct volume was significantly associated with neurological deterioration.
Conclusions: Cerebral embolisation is immanent to TEER-MV and predominantly occurs during device interaction with the MV. Improvements to the procedure may focus on this procedural step.
Background
To detect changes in biological processes, samples are often studied at several time points. We examined expression data measured at different developmental stages, or more broadly, historical data. Hence, the main assumption of our proposed methodology was the independence between the examined samples over time. In addition, however, the examinations were clustered at each time point by measuring littermates from relatively few mother mice at each developmental stage. As each examination was lethal, we had an independent data structure over the entire history, but a dependent data structure at a particular time point. Over the course of these historical data, we wanted to identify abrupt changes in the parameter of interest - change points.
Results
In this study, we demonstrated the application of generalized hypothesis testing using a linear mixed effects model as a possible method to detect change points. The coefficients from the linear mixed model were used in multiple contrast tests and the effect estimates were visualized with their respective simultaneous confidence intervals. The latter were used to determine the change point(s). In small simulation studies, we modelled different courses with abrupt changes and compared the influence of different contrast matrices. We found two contrasts, both capable of answering different research questions in change point detection: The Sequen contrast to detect individual change points and the McDermott contrast to find change points due to overall progression. We provide the R code for direct use with provided examples. The applicability of those tests for real experimental data was shown with in-vivo data from a preclinical study.
Conclusion
Simultaneous confidence intervals estimated by multiple contrast tests using the model fit from a linear mixed model were capable to determine change points in clustered expression data. The confidence intervals directly delivered interpretable effect estimates representing the strength of the potential change point. Hence, scientists can define biologically relevant threshold of effect strength depending on their research question. We found two rarely used contrasts best fitted for detection of a possible change point: the Sequen and McDermott contrasts.