Although mobile social networking sites have successfully penetrated into individual’s various aspects of everyday lives, few empirical studies have investigated important antecedents of civic involvement in the WeChat context from a network capital perspective. The principal aims of the research are to systematically explore the underlying associations between mobile social media use, network heterogeneity, network capital, and civic participation among young people. The data was collected in an online survey of 1,208 young people in mainland China. Structural equation modeling analysis was carried out to examine the corresponding hypotheses. Findings revealed that informational WeChat use could positively impact young people’s network heterogeneity, which subsequently contributes to increased degrees of civic involvement. Additionally, the results demonstrated that network heterogeneity and network capital on WeChat are positively associated with civic involvement. Furthermore, network heterogeneity and network capital could mediate the association between WeChat use for information and individual’s civic activities. These obtained outcomes underlined the vital role of mobile social media communication in facilitating democratic engagement of young citizens in contemporary mobile media-saturated society.
Weniger anzeigenThe US-Dollar (USD) holds a paramount position in the hierarchy of the International Monetary System (IMS). The significance of this currency has experienced a remarkable surge, leading to non-US banking systems to adopt new strategies for integrating themselves into the USD funding structure. Consequently, non-US banks have turned to new financial instruments and institutions to hedge their balance sheets effectively. While previous research has primarily focused on the Eurodollar market and FX swaps, the role of US banks in providing USD funding liquidity to these markets and instruments has been curtailed due to post-GFC regulations. This funding gap has been filled by US prime MMFs. Therefore, this paper investigates the emerging global dimension of unsecured funding liquidity provided by prime MMFs through wholesale funding instruments, namely commercial papers (CPs) and certificates of deposit (CDs), to the European and Japanese banking systems. Moreover, it examines the implications of this unsecured funding for JPY/USD and EUR/USD FX swaps markets. The paper argues that rates associated with CPs and CDs have become pivotal indicators of liquidity conditions in the offshore USD system. Disruptions in these markets can result in significant vulnerabilities in FX swaps markets, as evidenced during the pandemic crisis. Only through the Fed’s backstop strategy, implemented via swap lines and the Money Market Mutual Fund Liquidity Facility (MMLF), have the liquidity conditions of prime MMFs improved, yielding favorable outcomes for non-US banks.
Weniger anzeigenBased on indirect evidence, increased mucosal translocation of gut-derived microbial macromolecules has been proposed as an important pathomechanism in HIV infection. Here, we quantified macromolecule translocation across intestinal mucosa from treatment-naive HIV-infected patients, HIV-infected patients treated by combination antiretroviral therapy, and HIV-negative controls and analyzed the translocation pathways involved. Macromolecule permeability was quantified by FITC-Dextran 4000 (FD4) and horseradish peroxidase (HRP) flux measurements. Translocation pathways were addressed using cold inhibition experiments. Tight junction proteins were characterized by immunoblotting. Epithelial apoptosis was quantified and translocation pathways were further characterized by flux studies in T84 cell monolayers using inducers and inhibitors of apoptosis and endocytosis. In duodenal mucosa of untreated but not treated HIV-infected patients, FD4 and HRP permeabilities were more than a 4-fold increase compared to the HIV-negative controls. Duodenal macromolecule permeability was partially temperature-dependent and associated with epithelial apoptosis without altered expression of the analyzed tight junction proteins. In T84 monolayers, apoptosis induction increased, and both apoptosis and endocytosis inhibitors reduced macromolecule permeability. Using quantitative analysis, we demonstrate the increased macromolecule permeability of the intestinal mucosa in untreated HIV-infected patients. Combining structural and mechanistic studies, we identified two pathways of increased macromolecule translocation in HIV infection: transcytosis and passage through apoptotic leaks.
Weniger anzeigenThe essential trace elements copper, selenium and zinc are of relevance for immunity and immune response to vaccination. In this longitudinal study, adult healthcare workers (n = 126) received two doses of an mRNA vaccine (BNT162b2), and longitudinal serum samples were prepared. Vaccine-induced antibodies and their neutralizing activity were analyzed, and the trace elements copper, zinc, and selenium along with the copper transporter ceruloplasmin were measured. Subjects with combined deficiency of copper and zinc, i.e. both in the lowest tertiles at baseline, displayed particularly low antibody titers at three (Double Q1: 13 AU/mL vs. not double Q1: 29 AU/mL) and six (Double Q1: 200 AU/mL vs. not double Q1: 425 AU/mL) weeks after vaccination (p < 0.05). The results indicate the potential importance of an adequate trace element status of copper and zinc for raising a strong vaccine-induced SARS-CoV-2 antibody response, and highlights the importance of considering combined micronutrient insufficiencies, as single deficiencies may synergize.
Weniger anzeigenChronic Fatigue Syndrome (CFS) presents with symptoms of hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, thyroid hormone (TH) profiles of elevated thyrotropin and low thyroxine (T4) are not consistently observed. Recently, autoantibodies to the Se transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto's thyroiditis and shown to impair selenoprotein expression. We hypothesized that SELENOP-aAb are prevalent in CFS, and associate with reduced selenoprotein expression and impaired TH deiodination.
Se status and SELENOP-aAb prevalence was compared by combining European CFS patients (n = 167) and healthy controls (n = 545) from different sources. The biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP showed linear correlations across the samples without reaching saturation, indicative of Se deficiency. SELENOP-aAb prevalence was 9.6-15.6% in CFS versus 0.9-2.0% in controls, depending on cut-off for positivity. The linear correlation between Se and GPx3 activity was absent in SELENOP-aAb positive patients, suggesting impaired Se supply of kidney. A subgroup of paired control (n = 119) and CSF (n = 111) patients had been characterized for TH and biochemical parameters before. Within this subgroup, SELENOP-aAb positive patients displayed particularly low deiodinase activity (SPINA-GD index), free T3 levels, total T3 to total T4 (TT3/TT4) and free T3 to free T4 (FT3/FT4) ratios. In 24 h urine, iodine concentrations were significantly lower in SELENOP-aAb positive than in SELENOP-aAb negative patients or controls (median (IQR); 43.2 (16.0) vs. 58.9 (45.2) vs. 89.0 (54.9) & mu;g/L). The data indicate that SELENOP-aAb associate with low deiodination rate and reduced activation of TH to active T3.
We conclude that a subset of CFS patients express SELENOP-aAb that disturb Se transport and reduce sele-noprotein expression in target tissues. Hereby, TH activation decreases as an acquired condition not reflected by thyrotropin and T4 in blood. This hypothesis opens new diagnostic and therapeutic options for SELENOP-aAb positive CFS, but requires clinical evidence from intervention trials.
Weniger anzeigenBackground: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. Results: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up (p < 0.001). AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF (r = −0.479, p < 0.001), LV GLS (r = 0.441, p < 0.001) and LV GCS (r = 0.396, p = 0.001) as well as between AAR and LVEF (r = −0.430, p = 0.003), LV GLS (r = 0.501, p < 0.001) and weak with LV GCS (r = 0.342, p = 0.020). At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation (r = −0.347, p = 0.021). Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. Conclusion: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI.
Weniger anzeigenPercutaneous left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited. The aim of this study was to analyze outcomes of peri-procedural safety and healthcare resource utilization in 11,240 adult patients undergoing LAAC in the United States between 2016 and 2019. Primary outcomes (safety) were in-hospital ischemic stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolization and mortality. Secondary outcomes (resource utilization) were adverse discharge disposition, hospital length of stay (LOS) and costs. Logistic and Poisson regression models were used to analyze outcomes by adjusting for 10 confounders. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0-0.24] (p = 0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality (0.14%) remained stable. Hospital LOS decreased by 17% (0.78-0.87, p < 0.001) and adverse discharge rate by 41% (95% CI 0.41-0.86, p = 0.005) between 2016 and 2019, while hospital costs did not significantly change (p = 0.2). Female patients had a higher risk of PE (OR 2.86 [95% CI 2.41-6.39]) and SE (OR 5.0 [95% CI 1.28-43.6]) while multi-morbid patients had higher risks of major bleeding (p < 0.001) and mortality (p = 0.031), longer hospital LOS (p < 0.001) and increased treatment costs (p = 0.073). Significant differences in all outcomes were observed between male and female patients across US regions. In conclusion, LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.
Weniger anzeigenBackground: Selenium is essential for expression and proper function of a set of redox active selenoproteins implicated in aging-relevant diseases, e.g. type 2 diabetes mellitus (T2D) and hypertension. However, data in cohorts of older adults, particularly with respect to different Se biomarkers and sex-specific analyses are sparse.
Objective: To assess associations of serum Se and selenoprotein P (SELENOP) concentrations with T2D and hypertension in a cohort of older females and males.
Methods: This study included 1500 participants from the Berlin Aging Study II. Diagnosis of T2D was made in case of antidiabetic medication, self-reported T2D, or laboratory parameters. Diagnosis of hypertension was based on self-report, blood pressure measurement, or anti-hypertensive medication. Se was measured by spectroscopy, and SELENOP by ELISA. Multiple adjusted regression models quantified dose-dependent associations.
Results: Participants had a median(IQR) age of 68 (65,71) years, and 767 (51%) were women. 191 (13%) participants had T2D and 1126 (75%) had hypertension. Se and SELENOP correlated significantly (r = 0.59, p < 0.001), and were elevated in those with self-reported Se supplementation. Serum Se and SELENOP were not associated with T2D in the whole cohort. In men, SELENOP was positively associated with T2D, OR (95%CI) for one mg/L increase in SELENOP was 1.22 (1.00,1.48). Se was non-linearly associated with hypertension, comparing to the lowest quartile (Q1), and participants with higher Se levels (Q3) had a lower OR (95%CI) of 0.66 (0.45,0.96), which was specific for men. SELENOP positively associated with hypertension, and OR (95%CI) per one mg/L increase was 1.15 (1.01,1.32).
Conclusions: The data suggest a sex-specific interrelationship of Se status with T2D and hypertension, with apparent biomarker-specific associations.
Weniger anzeigenThe activation of the mineralocorticoid (MR) and glucocorticoid (GR) receptors on peripheral sensory neurons seems to modify pain perception through both direct non-genomic and indirect genomic pathways. These distinct subpopulations of sensory neurons are not known for peripheral human nerves. Therefore, we examined MR and GR on subpopulations of sensory neurons in sectioned human and rat peripheral nerves. Real-time PCR (RT-PCR) and double immunofluorescence confocal analysis of MR and GR with the neuronal markers PGP9.5, neurofilament 200 (NF200), and the potential pain signaling molecules CGRP, Nav1.8, and TRPV1 were performed in human and rat nerve tissue. We evaluated mechanical hyperalgesia after intrathecal administration of GR and MR agonists. We isolated MR- and GR-specific mRNA from human peripheral nerves using RT-PCR. Our double immunofluorescence analysis showed that the majority of GR colocalized with NF200 positive, myelinated, mechanoreceptive A-fibers and, to a lesser extent, with peripheral peptidergic CGRP-immunoreactive sensory nerve fibers in humans and rats. However, the majority of MR colocalized with CGRP in rat as well as human nerve tissue. Importantly, there was an abundant colocalization of MR with the pain signaling molecules TRPV1, CGRP, and Nav1.8 in human as well as rat nerve tissue. The intrathecal application of the GR agonist reduced, and intrathecal administration of an MR agonist increased, mechanical hyperalgesia in rats. Altogether, these findings support a translational approach in mammals that aims to explain the modulation of sensory information through MR and GR activation. Our findings show a significant overlap between humans and rats in MR and GR expression in peripheral sensory neurons.
Weniger anzeigenHigher perspective taking skills are associated with better social functioning and improved social relationships. Generally, teachers are willing to take the perspective of their students, but it is unclear whether the same is true for the perspective of parents. As communication and conflicts with parents are pervasive, the motivation and willingness to adopt the perspective of parents in counseling situations should be promoted during university teacher training. Therefore, we investigated the promotion of perspective taking among teachers in training and focused mainly on perspective taking toward parents. We developed a case-based learning task in which teachers in training from Freie Universität Berlin (N = 515) prepared for a fictitious upcoming consultation with a mother about her son. Because it is unclear if direct instruction for perspective taking is necessary in order to promote it, we also used indirect instruction to investigate whether preparing for the consultation under these instructions fostered the willingness to adopt the perspective of students and parents. In the direct instruction participants were directly told to take the perspective of the fictitious mother when evaluating and developing formulations for the consultation. The indirect instruction did not mention the concept of perspective taking but asked participants to focus on the comprehensibility of the formulations. We obtained three measures: the willingness to take a perspective, the attitude toward another person, and the emotional and empathic language used in written texts. With our main result we demonstrated that the willingness to adopt the perspective of both students and parents could be significantly promoted by both instructions. We further demonstrated that a higher willingness to take another’s perspective is associated with a more positive attitude toward the mother, as well as increased positive emotions and empathic concern. Additionally, we replicated results of a previous study showing a generally higher willingness to take the student perspective prior to the intervention. Results are discussed regarding the benefits of promoting perspective taking, especially toward parents, in teacher education.
Weniger anzeigenMammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in the pathogenesis of inflammatory diseases, and its pro- and anti-inflammatory effects have been reported for different ALOX-isoforms. Human ALOX15B oxygenates arachidonic acid to its 15-hydroperoxy derivative, whereas the corresponding 8-hydroperoxide is formed by mouse Alox15b (Alox8). This functional difference impacts the biosynthetic capacity of the two enzymes for creating pro- and anti-inflammatory eicosanoids. To explore the functional consequences of the humanization of the reaction specificity of mouse Alox15b in vivo, we tested Alox15b knock-in mice that express the arachidonic acid 15-lipoxygenating Tyr603Asp and His604Val double mutant of Alox15b, instead of the arachidonic acid 8-lipoxygenating wildtype enzyme, in two different animal inflammation models. In the dextran sodium sulfate-induced colitis model, female Alox15b-KI mice lost significantly more bodyweight during the acute phase of inflammation and recovered less rapidly during the resolution phase. Although we observed significant differences in the colonic levels of selected pro- and anti-inflammatory eicosanoids during the time-course of inflammation, there were no differences between the two genotypes at any time-point of the disease. In Freund's complete adjuvant-induced paw edema model, Alox15b-KI mice were less susceptible than outbred wildtype controls, though we did not observe significant differences in pain perception (Hargreaves-test, von Frey-test) when the two genotypes were compared. our data indicate that humanization of the reaction specificity of mouse Alox15b (Alox8) sensitizes mice for dextran sodium sulfate-induced experimental colitis, but partly protects the animals in the complete Freund's adjuvant-induced paw edema model.
Weniger anzeigenHeart failure is the leading cause of morbidity and mortality and currently affects more than 60 million people worldwide. A key feature in the pathogenesis of almost all forms of heart failure is cardiac fibrosis, which is characterized by excessive accumulation of extracellular matrix components in the heart. Although cardiac fibrosis is beneficial in the short term after acute myocardial injury to preserve the structural and functional integrity of the heart, persistent cardiac fibrosis contributes to pathological cardiac remodeling, leading to mechanical and electrical dysfunction of the heart. Despite its high prevalence, standard therapies specifically targeting cardiac fibrosis are not yet available. Cell-based approaches have been extensively studied as potential treatments for cardiac fibrosis, but several challenges have been identified during clinical translation. The observation that extracellular vesicles (EVs) derived from stem and progenitor cells exhibit some of the therapeutic effects of the parent cells has paved the way to overcome limitations associated with cell therapy. However, to make EV-based products a reality, standardized methods for EV production, isolation, characterization, and storage must be established, along with concrete evidence of their safety and efficacy in clinical trials. This article discusses EVs as novel therapeutics for cardiac fibrosis from a translational perspective.
Weniger anzeigenBackground: Clinical trial registries allow assessment of deviations of published trials from their protocol, which may indicate a considerable risk of bias. However, since entries in many registries can be updated at any time, deviations may go unnoticed. We aimed to assess the frequency of changes to primary outcomes in different historical versions of registry entries, and how often they would go unnoticed if only deviations between published trial reports and the most recent registry entry are assessed.
Methods and findings: We analyzed the complete history of changes of registry entries in all 1746 randomized controlled trials completed at German university medical centers between 2009 and 2017, with published results up to 2022, that were registered in ClinicalTrials.gov or the German WHO primary registry (German Clinical Trials Register; DRKS). Data were retrieved on 24 January 2022. We assessed deviations between registry entries and publications in a random subsample of 292 trials. We determined changes of primary outcomes (1) between different versions of registry entries at key trial milestones, (2) between the latest registry entry version and the results publication, and (3) changes that occurred after trial start with no change between latest registry entry version and publication (so that assessing the full history of changes is required for detection of changes). We categorized changes as major if primary outcomes were added, dropped, changed to secondary outcomes, or secondary outcomes were turned into primary outcomes. We also assessed (4) the proportion of publications transparently reporting changes and (5) characteristics associated with changes. Of all 1746 trials, 23% (n = 393) had a primary outcome change between trial start and latest registry entry version, with 8% (n = 142) being major changes, that is, primary outcomes were added, dropped, changed to secondary outcomes, or secondary outcomes were turned into primary outcomes. Primary outcomes in publications were different from the latest registry entry version in 41% of trials (120 of the 292 sampled trials; 95% confidence interval (CI) [35%, 47%]), with major changes in 18% (54 of 292; 95% CI [14%, 23%]). Overall, 55% of trials (161 of 292; 95% CI [49%, 61%]) had primary outcome changes at any timepoint over the course of a trial, with 23% of trials (67 of 292; 95% CI [18%, 28%]) having major changes. Changes only within registry records, with no apparent discrepancy between latest registry entry version and publication, were observed in 14% of trials (41 of 292; 95% CI [10%, 19%]), with 4% (13 of 292; 95% CI [2%, 7%]) being major changes. One percent of trials with a change reported this in their publication (2 of 161 trials; 95% CI [0%, 4%]). An exploratory logistic regression analysis indicated that trials were less likely to have a discrepant registry entry if they were registered more recently (odds ratio (OR) 0.74; 95% CI [0.69, 0.80]; p<0.001), were not registered on ClinicalTrials.gov (OR 0.41; 95% CI [0.23, 0.70]; p = 0.002), or were not industry-sponsored (OR 0.29; 95% CI [0.21, 0.41]; p<0.001). Key limitations include some degree of subjectivity in the categorization of outcome changes and inclusion of a single geographic region.
Conclusions: In this study, we observed that changes to primary outcomes occur in 55% of trials, with 23% trials having major changes. They are rarely transparently reported in the results publication and often not visible in the latest registry entry version. More transparency is needed, supported by deeper analysis of registry entries to make these changes more easily recognizable.
Weniger anzeigenSuperficial erythematous cutaneous vascular malformations are assumed to be blood vascular in origin, but cutaneous lymphatic malformations can contain blood and appear red. Management may be different and so an accurate diagnosis is important. Cutaneous malformations were investigated through 2D histology and 3D whole-mount histology. Two lesions were clinically considered as port-wine birthmarks and another 3 lesions as erythematous telangiectasias. The aims were (i) to demonstrate that cutaneous erythematous malformations including telangiectasia can represent a lymphatic phenotype, (ii) to determine if lesions represent expanded but otherwise normal or malformed lymphatics, and (iii) to determine if the presence of erythrocytes explained the red color. Microscopy revealed all lesions as lymphatic structures. Port-wine birthmarks proved to be cystic lesions, with nonuniform lymphatic marker expression and a disconnected lymphatic network suggesting a lymphatic malformation. Erythematous telangiectasias represented expanded but nonmalformed lymphatics. Blood within lymphatics appeared to explain the color. Blood-lymphatic shunts could be detected in the erythematous telangiectasia. In conclusion, erythematous cutaneous capillary lesions may be lymphatic in origin but clinically indistinguishable from blood vascular malformations. Biopsy is advised for correct phenotyping and management. Erythrocytes are the likely explanation for color accessing lymphatics through lympho-venous shunts.
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