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AimsCardiomyopathy in Fabry disease (FD) is a major determinant of morbidity and mortality. This study investigates the effects of FD-specific treatment using enzyme replacement therapy (ERT) and chaperone therapy on left atrial (LA) function using two-dimensional speckle tracking echocardiography (2DSTE).Methods and resultsIn this prospective observational single-center study, 20 FD patients [10 (50%) females] treated with migalastat, 48 FD patients [24 (50%) females] treated with ERT (agalsidase-alfa and agalsidase-beta), and 30 untreated FD patients (all females) as controls were analyzed. The mean follow-up time ranged from 26 to 81 months. 2DSTE was performed for left ventricle strain, right ventricle strain, and LA strain (LAS). FD-specific treated patients presented with increased left ventricular mass index (LVMi) and higher frequency of left ventricular hypertrophy at baseline, whereas untreated control patients showed normal baseline values. FD-specific treated (including migalastat and ERT) patients showed stabilization of LAS over time (p > 0.05). LVMi was also stable in treated FD patients during observation (p > 0.05).ConclusionIn patients with FD, treated with either ERT or chaperone therapy, LAS values measured by echocardiographic speckle tracking were stable over time, pointing toward disease stabilization.

Polyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the de novo formation of functional anti-PEG antibodies in a healthy male after the second mRNA-based vaccination against SARS-CoV-2. Consequently, we analyzed the frequency and inhibitory function of anti-PEG and anti-α-Galactosidase A (AGAL) antibodies in 102 FD patients (46.9% males). We identified 29 out of 87 (33.3%) patients with low anti-PEG titers. Sera from patients without anti-AGAL antibodies [n=70] showed a higher rescued AGAL activity of agalsidase-beta and PRX-102 [both p

Restoration of the degraded rangelands in Jordan using mechanized water harvesting and native species planting has become key to enhancing and maintaining the productivity and resilience of fragile ecosystems. A balanced interaction between the rangeland's hydrology and vegetation states is vital for achieving long-term sustainability. To gain a better insight into the impact of restoration on surface runoff and erosion and its role in recovering the ecosystem functions, we used the Rangeland Hydrological and Erosion Model (RHEM) to simulate various vegetation scenarios. Our research aims to understand the rangelands' water and sediment dynamics and the vegetation transition states of the ecosystem through evaluating the current (degraded) situation, assess the restoration approach on improving the degraded status (restored), and investigate the long-term sustainability of the restoration approach compared with historical rangeland conditions (baseline). Several scenarios were developed with rangeland experts, local community representatives, and measurements at protected and restored areas to represent the rangeland conditions. We found that restoration of the degraded Badia areas will decrease annual surface runoff from an average of 23.5 to 19.1 mm/year and soil erosion rate from 3.3 to 1.3 tons/ha. With time, restoration can bring back rangeland water and sediment dynamics closer towards the baseline conditions, which were 16.9 mm/year runoff rates and 0.85 ton/ha/year soil loss. The results indicate that restoration is a promising methodology to restore the degraded ecosystem and approximate the environment's historical hydrological regime.

Purpose: This study analyzed the physiological response during Yo-Yo Intermittent Recovery Level 1 (YYIR1) test and re-test by in-field ergospirometry and time-series analyses of respiratory parameters. Methods: Ten moderately trained males (23.4 ± 2.01 years, VO[subscript 2peak]= 56.81 ± 10.75 mL·kg[superscript -1]·min[superscript -1]) completed three running trials including two separate YYIR1 tests and an independent maximal performance running test with time-series analyses of gas exchange parameters. Physiological response was assessed during all tests by determination of blood lactate levels (including calculation of individual lactate threshold), heart rate, oxygen consumption and respiratory exchange ratio (RER). Results: Modeling of YYIR1 test mean VO[subscript 2] uptake kinetics over all participants revealed that VO[subscript 2] increased rapidly after the individual lactate threshold (11.49 ± 0.66 km·h[superscript -1] at 3.83 ± 0.42 mmol·L[superscript -1]) was reached with ~95% VO[subscript 2peak] at ~50% of the test duration (test, VO[subscript 2][superscript 50%]= 95.17 ± 8.74% of VO[subscript 2peak]; re-test, VO[subscript 2][superscript 50%]= 96.78 ± 7.04% of VO[subscript 2peak]). However, and despite identical YYIR1 test performance (1568 ± 364.6 m vs. 1568 ± 449.7 m, CV = 4.59%), mean VO[subscript 2peak] during YYIR1 test was 8.81 ± 5.6% higher than YYIR1 re-test (p = 0.027). Importantly, correlation of VO[subscript 2peak] with YYIR1 test performance was weak (R[superscript 2] = 0.28, p = 0.115). Conclusions: We conclude that the YYIR1 test should not be used to estimate VO[subscript 2peak]. Further studies on direct determination of gas exchange parameters during different YYI test variants are warranted.

Background and Objectives: Abdominal trauma among severely injured patients with an injury severity score (ISS) of 16 and above can lead to potentially life-threatening injuries that might need immediate surgical intervention. Traumatic injuries to the diaphragm (TID) are a challenging condition often accompanied by other injuries in the thoracoabdominal region. Materials and Methods: We retrospectively analyzed the occurrence and clinical course of TID among severely injured patients treated at our center between 2008 and 2019 and compared them to other groups of severely injured patients without TID. Results: Thirty-five patients with TID and a median ISS of 41 were treated in the period mentioned above. They were predominantly middle-aged men and mostly victims of blunt trauma as a consequence of motor vehicle accidents. A total of 70.6% had left-sided TID, and in 69.6%, the size of defect was larger than 10 cm. The diagnosis was made with computed tomography (CT) in 68.6% of the cases, while in 25.8%, it was made intraoperatively or delayed by a false-negative initial CT scan, and in 5.7%, an intraoperative diagnosis was made without preoperative CT imaging. Surgical repair was mostly conducted via laparotomy, performing a direct closure with continuous suture. A comparison to 191 patients that required laparotomy for abdominal injuries other than TID revealed significantly higher rates of concomitant injuries to several abdominal organs among patients suffering from TID. Compared to all other severely injured patients treated in the same period (n = 1377), patients suffering from TID had a significantly higher median ISS and a longer mean duration of hospital stay. Conclusions: Our findings show that TID can be seen as an indicator of particularly severe thoracoabdominal trauma that requires increased attention from the treatment team so as not to miss relevant concomitant injuries that require immediate intervention.

Nitriding of Fe-1 wt.% Cu and Fe-5 wt.% Cu alloys at 813 K leads to the formation of predominantly the γ′-iron nitride phase (γ′-Fe4N) when using nitriding conditions, which lead to pronounced formation of ε-iron nitride phase (ε-Fe3N1+x) upon nitriding of pure α-Fe. Energy dispersive X-ray analysis reveals that the developing γ′ can attain a Cu content corresponding to that of the base material. In contrast, tiny amounts of ε-nitride that eventually develop contain considerably less Cu. The microstructure implies that the formation of the ε-nitride requires long-range substitutional interdiffusion to achieve the Cu partitioning. These observations were interpreted in terms of a significantly higher solubility of Cu in the γ′ phase than in the ε phase, which is explainable by the phases’ crystal structures. The observations were rationalized in terms of schematic Fe–Cu–N phase diagrams valid for 813 K.

Background: High-intensity interval training (HIIT) is a well-established training modality to improve aerobic and anaerobic capacity. However, sex-specific aspects of different HIIT protocols are incompletely understood. This study aimed to compare two HIIT protocols with different recovery periods in moderately trained females and males and to investigate whether sex affects high-intensity running speed and speed decrement.Methods: Fifty moderately trained participants (30 females and 20 males) performed an exercise field test and were randomized by lactate threshold (LT) to one of two time- and workload-matched training groups. Participants performed a 4-week HIIT intervention with two exercise sessions/week: Group 1 (4 × 30,180 HIIT), 30-s all-out runs, 180-s active recovery and Group 2 (4 × 30,30 HIIT), 30-s all-out runs, 30-s active recovery. High-intensity runs were recorded, and speed per running bout, average speed per session, and speed decrement were determined. Blood lactate measurements were performed at baseline and follow-up at rest and immediately post-exercise.Results: Females and males differed in running speed at LT and maximal running speed determined during exercise field test (speed at LT, females: 10.65 ± 0.84 km h−1, males: 12.41 ± 0.98 km h−1, p < 0.0001; maximal speed, females: 14.55 ± 1.05 km h−1, males: 17.41 ± 0.68 km h−1, p < 0.0001). Estimated maximal oxygen uptake was ~52.5 ml kg−1 min−1 for females and 62.6 ml kg−1 min−1 for males (p < 0.0001). Analysis of HIIT protocols revealed an effect of sex on change in speed decrement (baseline vs. follow-up) in that females showed significant improvements only in the 4 × 30:30 HIIT group (p = 0.0038). Moreover, females performing the 4 × 30:30 protocol presented increased speed per bout and average speed per session at follow-up (all p ≤ 0.0204), while no effect was detected for females performing the 4 × 30:180 protocol. Peak blood lactate levels increased in all HIIT groups (all p < 0.05, baseline vs. follow-up), but males performing the 4 × 30:180 protocol showed no difference in lactate levels.Conclusions: If not matched for physical performance, females, but not males, performing a 4 × 30 HIIT protocol with shorter recovery periods (30 s) present increased average high-intensity running speed and reduced speed decrement compared to longer recovery periods (180 s). We conclude that female- and male-specific HIIT protocols should be established since anthropometric and physiological differences across sexes may affect training performance in real-world settings.

Abstract Background KIBRA has been suggested as a key regulator of the Hippo signaling pathway, regulating organ size, cell contact inhibition, tissue regeneration as well as tumorigenesis and cystogenesis. We recently reported that human KIBRA expression depends on a complex alternative CpG-rich promoter system. Our current study aimed at the identification of epigenetic mechanisms associated with alterations in KIBRA expression regulation. Results We identified two separated methylation-sensitive CpG islands located to independent KIBRA promoter regions. In vitro promoter methylation analysis using human neuroblastoma (SH-SY5Y) and immortalized kidney cells (IHKE) revealed that total promoter methylation by CpG methyltransferase SssI resulted in complete abrogation of transcriptional activity (p

The diagnosis and prognosis of patients with severe chronic disorders of consciousness are still challenging issues and a high rate of misdiagnosis is evident. Hence, new tools are needed for an accurate diagnosis, which will also have an impact on the prognosis. In recent years, functional Magnetic Resonance Imaging (fMRI) has been gaining more and more importance when diagnosing this patient group. Especially resting state scans, i.e., an examination when the patient does not perform any task in particular, seems to be promising for these patient groups. After preprocessing the resting state fMRI data with a standard pipeline, we extracted the correlation matrices of 132 regions of interest. The aim was to find the regions of interest which contributed most to the distinction between the different patient groups and healthy controls. We performed feature selection using a genetic algorithm and a support vector machine. Moreover, we show by using only those regions of interest for classification that are most often selected by our algorithm, we get a much better performance of the classifier.

Optical coherence tomography angiography (OCT-A) represents the most recent modality in retinal imaging for non-invasive and depth-selective visualization of blood flow in retinal vessels. With regard to quantitative OCTA measurements for early detection of subclinical alterations, it is of great interest, which intra- and extra-ocular factors affect the results of OCTA measurements. Here, we performed OCTA imaging of the central retina in 65 eyes of 65 young healthy female and male participants and evaluated individual physical fitness levels by standard lactate diagnostic using an incremental maximal performance running test. The main finding was that OCTA measurements of the foveal avascular zone (FAZ) area were associated with physical fitness. Using multivariate regression analysis, we found that running speed at the individual lactate threshold, a marker strongly associated with aerobic performance capacity, significantly contributed to differences in FAZ area (β = 0.111, p = 0.032). The data indicates that smaller FAZ areas are likely observed in individuals with higher aerobic exercise capacity. Our findings are also of interest with respect to the potential use of retinal OCTA imaging to detect exercise-induced microvascular adaptations in future studies.

The ability to fabricate complex graded structures would be a significant step towards the manufacturing of material systems with properties tailored to individual applications. While powder metallurgy has had some success in this regard, it requires that the semi-finished products be exactly similar to the final component. However, it is significantly cheaper to produce simple, semi-finished products and then join them to form complex components with the desired graded structure through powder forging and simultaneous compaction. It is also essential that the graded structure of the semi-finished products is retained during the forming process. In this study, pre-sintered cylindrical semi-finished products consisting of identical homogeneous layers as well as graded components consisting of non-identical homogeneous layers were joined using powder forging at 1100 °C. The microstructures and densities as well as the mechanical properties of the final components were investigated. It was observed that, upon compaction, the components formed solid structures, in which the reinforcing ZrO2 particles were completely integrated within the transformation-induced plasticity steel matrix. Finally, it was confirmed that the graded structure of the semi-finished products was retained in the final components.

Background: Although Yo-Yo intermittent tests are frequently used in a variety of sports and research studies to determine physical fitness, no structured reference exists for comparison and rating of test results. This systematic review of the most common Yo-Yo tests aimed to provide reference values for test results by statistical aggregation of published data.Methods: A systematic literature search for articles published until August 2017 was performed in MEDLINE, Web of Science, SPORTDiscus and Google Scholar. Original reports on healthy females and males ≥16 years were eligible for the analysis. Sub-maximal test versions and the Yo-Yo Intermittent Recovery Level 1 Children's test (YYIR1C) were not included.Results: 248 studies with 9,440 participants were included in the structured analysis. The Yo-Yo test types most frequently used were the Yo-Yo Intermittent Recovery Level 1 (YYIR1, 57.7%), the Yo-Yo Intermittent Recovery Level 2 (YYIR2, 28.0%), the Yo-Yo Intermittent Endurance Level 2 (YYIE2, 11.4%), and the Yo-Yo Intermittent Endurance Level 1 (YYIE1, 2.9%) test. For each separate test, reference values (global means and percentiles) for sports at different levels and both genders were calculated.Conclusions: Our analysis provides evidence that Yo-Yo intermittent tests reference values differ with respect to the type and level of sport performed.The presented results may be used by practitioners, trainers and athletes to rate Yo-Yo intermittent test performance levels and monitor training effects.