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Abstract Background To increase the image quality of end-expiratory and end-inspiratory phases of retrospective respiratory self-gated 4D MRI data sets using non-rigid image registration for improved target delineation of moving tumors. Methods End-expiratory and end-inspiratory phases of volunteer and patient 4D MRI data sets are used as targets for non-rigid image registration of all other phases using two different registration schemes: In the first, all phases are registered directly (dir-Reg) while next neighbors are successively registered until the target is reached in the second (nn-Reg). Resulting data sets are quantitatively compared using diaphragm and tumor sharpness and the coefficient of variation of regions of interest in the lung, liver, and heart. Qualitative assessment of the patient data regarding noise level, tumor delineation, and overall image quality was performed by blinded reading based on a 4 point Likert scale. Results The median coefficient of variation was lower for both registration schemes compared to the target. Median dir-Reg coefficient of variation of all ROIs was 5.6% lower for expiration and 7.0% lower for inspiration compared with nn-Reg. Statistical significant differences between the two schemes were found in all comparisons. Median sharpness in inspiration is lower compared to expiration sharpness in all cases. Registered data sets were rated better compared to the targets in all categories. Over all categories, mean expiration scores were 2.92 ± 0.18 for the target, 3.19 ± 0.22 for nn-Reg and 3.56 ± 0.14 for dir-Reg and mean inspiration scores 2.25 ± 0.12 for the target, 2.72 ± 215 0.04 for nn-Reg and 3.78 ± 0.04 for dir-Reg. Conclusions In this work, end-expiratory and inspiratory phases of a 4D MRI data sets are used as targets for non-rigid image registration of all other phases. It is qualitatively and quantitatively shown that image quality of the targets can be significantly enhanced leading to improved target delineation of moving tumors.

Abstract Rhabdomyolysis (RM) is a potentially life‐threatening entity that can lead to acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) alone is known as effective therapy, but the additional use of a hemoadsorber (like CytoSorb®) might increase its efficacy.

Background: The ‘Western diet’ typically consumed in industrialized countries is characterized by high amounts of processed cereal grains and animal products while being low in vegetables, tubers, and fruits. This dietary behavior leads to imbalances of acid–base status in favor of the acids and may cause low-grade metabolic acidosis (LGMA) that is associated with negative effects on health in the long run, including urolithiasis, bone loss, and even cardiometabolic diseases. Therefore, it has become of great interest to find dietary strategies that can be used to neutralize the acid load associated with Western diets. Objective: The aim of this study was to investigate whether the diet-dependent net acid load can be reduced by the daily consumption of mineral waters with different bicarbonate content and different potential renal acid load (PRAL). Methods: A single-centered, randomized trial including 129 healthy men and women aged from 18 to 75 years was conducted. Participants consumed 1,500–2,000 mL of one of four mineral waters with different bicarbonate content and different PRAL values daily for 4 weeks: low bicarbonate, high PRAL (LBHP, HCO3−: 403.0 mg/L, PRAL: 10.7); medium-high bicarbonate, medium PRAL (MBMP, HCO3− : 1816.0 mg/L, PRAL: −10.8); high bicarbonate, low PRAL (HBLP, HCO3−: 2451.0 mg/L, PRAL: −19.3); medium-high bicarbonate, low PRAL (MBLP, HCO3−: 1846.0 mg/L, PRAL: −22.1). Throughout the study, participants were asked to maintain their usual dietary habits. The primary outcome was the net acid excretion (NAE) measured in the 24-h urine output. Results: Consumption of the three mineral waters: MBMP, HBLP, and MBLP led to a significant decrease in NAE values. Within the MBMP group, the NAE could be reduced by 48% (P = 0.001), while consumption of HBLP led to a reduction of 68% (P < 0.001) and MBLP to a reduction of 53% (P = 0.001). Moreover, a slight increase in serum bicarbonate could also be observed in the groups that drank HBLP (P = 0.057) and MBLP (P = 0.001). Conclusion: Daily consumption of at least 1,500–2,000 mL of mineral water rich in bicarbonate (>1800.0 mg/L) with medium or low PRAL (

Summary: Converging evidence indicates that major depressive disorder (MDD) and metabolic disorders might be mediated by shared (patho)biological pathways. However, the converging cellular and molecular signatures remain unknown. Here, we investigated metabolic dysfunction on a systemic, cellular, and molecular level in unmedicated patients with MDD compared with matched healthy controls (HC). Despite comparable BMI scores and absence of cardiometabolic disease, patients with MDD presented with significant dyslipidemia. On a cellular level, T cells obtained from patients with MDD exhibited reduced respiratory and glycolytic capacity. Gene expression analysis revealed increased carnitine palmitoyltransferase IA (CPT1a) levels in T cells, the rate-limiting enzyme for mitochondrial long-chain fatty acid oxidation. Together, our results indicate metabolic dysfunction in unmedicated, non-overweight patients with MDD on a systemic, cellular, and molecular level. This evidence for reduced mitochondrial respiration in T cells of patients with MDD provides translation of previous animal studies regarding a putative role of altered immunometabolism in depression pathobiology.

Adapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24 h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.

Abstract In vitro determination of the hemoglobin oxygen dissociation curve (ODC) requires highly elaborate, specialized, and costly technical equipment. In addition, there is a lack of methods that combine reliable ODC recordings with high throughput in small blood samples for routine analysis. We here introduce a modified, commercial 96‐well plate with an integrated unidirectional gas flow system specifically adapted for use in fluorescence microplate readers. Up to 92 samples of whole or hemolyzed, buffered or unbuffered blood, including appropriate controls or internal standard hemoglobin solutions, can be analyzed within ~25 min. Oxygen saturation is measured in each well with dual wavelength spectroscopy, and oxygen partial pressure using fluorescence lifetime of commercial oxygen sensors at the in‐ and outlet ports of the gas‐flow system. Precision and accuracy of this method have been determined and were compared with those of a standard method. We further present two applications that exemplarily highlight the usefulness and impact of this novel approach for clinical diagnostics or basic research.

The integration of intermittent renewable energy sources into the electricity market requires flexible and efficient technologies that compensate for the fluctuating electricity demand. A circulating fluidized bed (CFB) boiler is a suitable solution due to its fuel flexibility, but the thermal inertia of the fluidized bed can have negative effects on the load following capabilities. This study investigates the influence of the operating parameters of the fire side on the speed of load changes on the waterside. Co-combustion of lignite, straw, and refuse derived fuel (RDF) was carried out. In a 1 MWth pilot CFB combustor fifteen load changes were performed with a varying step input of the primary air, the secondary air, and the fuel mass flow. The step input of the primary air had a large influence on the load ramps, as it strongly affects the solids concentration in the upper furnace. The step size of the fuel mass flow had a positive effect on the load change rate. Based on the results, concepts were developed to accelerate load ramping by controlling the hydrodynamic conditions and the temperature on the fireside.

The increasing share of renewable energy sources draws attention to a critical challenge [...]

Abstract Background Military families who have a family member with a mental illness see themselves confronted with many demands. Stigmatization is one of these challenges. Stigmatization affects not only the individual who suffers from a mental illness but also other family members via stigma by association and vicarious stigma. Stigma by association occurs when mental illness stigma spills over to individuals associated with an individual with a mental illness. Vicarious stigma describes the suffering of family members when they note the impact of stigma on their relative with mental illness. As a societal phenomenon, stigma plays out in social interactions and might therefore influence the social networks of families. It is also associated with healthcare utilization. Method Narrative interviews were conducted with 15 family members (partners, spouses, parents and children) of former soldiers of the German Armed Forces with a service-induced mental illness. The transcribed interview data were analyzed using a thematic analysis approach, in which codes were formed and emerging themes were systemized. Relationships between stigma, the families’ reactions to it, its effects on their social relationships and its interference with their healthcare utilization were analyzed. Results This study provides a detailed description of how relatives of former German soldiers with mental health problems experience stigma by association and vicarious stigma. Their perceptions are shown in a model that describes stigma-related attitudes, reactions to them and their effects on the social relationships of former soldiers’ families. These families felt stigmatized because of the former soldiers’ mental illness (mental illness stigma) and the military context in which it occurred (former soldier stigma). They reacted with nondisclosure, anger, acceptance and self-blame. Stigma was associated with smaller and weaker social networks that were characterized by social exclusion, self-segregation and conflicts with extended family, friends and colleagues. Stigma also affected the families’ healthcare utilization. Conclusions Urgently needed anti-stigma campaigns, particularly in the civilian context, should address the stigmatization of both mental illness and the military participation of the families affected. They should consider the needs of both former soldiers with a mental illness and their families.