The Relationship Between Early Maladaptive Schemas and Cluster C Personality Disorder Traits: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: We systematically reviewed and meta-analyzed the literature on the relationship between early maladaptive schemas (EMSs) and Cluster C personality disorders (PDs). Our aim was to clarify which of the 18 EMSs exhibit the strongest associations and are most frequently endorsed in clinical and non-clinical samples with Cluster C PDs and traits. RECENT FINDINGS: After initially screening 2622 records, 12 studies were selected with 5310 participants. Meta-analyses of the raw correlation coefficients for each EMS-Cluster C PD link (3-8 studies per meta-analysis) indicated that the 18 EMSs were significantly related to all three Cluster C PDs with r's ranging from .13 to .63. However, when considering endorsement rates among multiple regression studies that controlled for the EMSs intercorrelations and the effects of other PD traits and demographics, specific EMS constellations emerged for each Cluster C PD. Overall, the findings of the current paper suggest that Cluster C PDs might be conceptualized on the basis of a hybrid EMS model, in which all EMSs contribute to global personality dysfunction whereas specific EMS patterns reflect unique personality disorder style expressions. Longitudinal research with appropriate methodology is needed to draw more definite conclusions on the EMSs-Cluster C PDs relationships.

Bacterial extracellular vesicles repress the vascular protective factor RNase1 in human lung endothelial cells.

BACKGROUND: Sepsis is one of the leading causes of death worldwide and characterized by blood stream infections associated with a dysregulated host response and endothelial cell (EC) dysfunction. Ribonuclease 1 (RNase1) acts as a protective factor of vascular homeostasis and is known to be repressed by massive and persistent inflammation, associated to the development of vascular pathologies. Bacterial extracellular vesicles (bEVs) are released upon infection and may interact with ECs to mediate EC barrier dysfunction. Here, we investigated the impact of bEVs of sepsis-related pathogens on human EC RNase1 regulation. METHODS: bEVs from sepsis-associated bacteria were isolated via ultrafiltration and size exclusion chromatography and used for stimulation of human lung microvascular ECs combined with and without signaling pathway inhibitor treatments. RESULTS: bEVs from Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium significantly reduced RNase1 mRNA and protein expression and activated ECs, while TLR2-inducing bEVs from Streptococcus pneumoniae did not. These effects were mediated via LPS-dependent TLR4 signaling cascades as they could be blocked by Polymyxin B. Additionally, LPS-free ClearColi™ had no impact on RNase1. Further characterization of TLR4 downstream pathways involving NF-кB and p38, as well as JAK1/STAT1 signaling, revealed that RNase1 mRNA regulation is mediated via a p38-dependent mechanism. CONCLUSION: Blood stream bEVs from gram-negative, sepsis-associated bacteria reduce the vascular protective factor RNase1, opening new avenues for therapeutical intervention of EC dysfunction via promotion of RNase1 integrity. Video Abstract.

Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis.

Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As important resident immune cells, alveolar macrophages are located at the air-tissue interface where they comprise the first line of defence against inhaled microorganisms and particles. To date, little is known about the interplay between alveolar macrophages and OMVs from pathogenic bacteria. The immune response to OMVs and underlying mechanisms are still elusive. Here, we investigated the response of primary human macrophages to bacterial vesicles (Legionella pneumophila, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Streptococcus pneumoniae) and observed comparable NF-κB activation across all tested vesicles. In contrast, we describe differential type I IFN signalling with prolonged STAT1 phosphorylation and strong Mx1 induction, blocking influenza A virus replication only for Klebsiella, E.coli and Salmonella OMVs. OMV-induced antiviral effects were less pronounced for endotoxin-free Clear coli OMVs and Polymyxin-treated OMVs. LPS stimulation could not mimic this antiviral status, while TRIF knockout abrogated it. Importantly, supernatant from OMV-treated macrophages induced an antiviral response in alveolar epithelial cells (AEC), suggesting OMV-induced intercellular communication. Finally, results were validated in an ex vivo infection model with primary human lung tissue. In conclusion, Klebsiella, E.coli and Salmonella OMVs induce antiviral immunity in macrophages via TLR4-TRIF-signaling to reduce viral replication in macrophages, AECs and lung tissue. These gram-negative bacteria induce antiviral immunity in the lung through OMVs, with a potential decisive and tremendous impact on bacterial and viral coinfection outcome. Video Abstract.

A Mobile App for Measuring Real Time Fatigue in Patients with Multiple Sclerosis: Introducing the Fimo Health App.

Although fatigue is one of the most disabling symptoms of MS, its pathogenesis is not well understood yet. This study aims to introduce a new holistic approach to measure fatigue and its influencing factors via a mobile app. Fatigue is measured with different patient-reported outcome measures (Visual Analog Scale, Fatigue Severity Scale) and tests (Symbol Digit Modalities Test). The influencing vital and environmental factors are captured with a smartwatch and phone sensors. Patients can track these factors within the app. To individually counteract their fatigue, a fatigue course, based on the current treatment guidelines, was implemented. The course implies knowledge about fatigue and MS, exercises, energy-conservation management, and cognitive behavioral therapy. Based on the Transtheoretical Model of Behavior Change, the design of the Fimo health app follows the ten strategies of the process of change, which is a proven approach to designing health intervention programs. By monitoring fatigue and individual influencing factors, patients can better understand and manage their fatigue. They can share their data and insights about fatigue and its influencing factors with their doctors. Thus, they can receive individualized therapies and drug plans.

The clinical role of host and bacterial-derived extracellular vesicles in pneumonia.

Pneumonia is among the leading causes of morbidity and mortality worldwide. Due to constant evolution of respiratory bacteria and viruses, development of drug resistance and emerging pathogens, it constitutes a considerable health care threat. To enable development of novel strategies to control pneumonia, a better understanding of the complex mechanisms of interaction between host cells and infecting pathogens is vital. Here, we review the roles of host cell and bacterial-derived extracellular vesicles (EVs) in these interactions. We discuss clinical and experimental as well as pathogen-overarching and pathogen-specific evidence for common viral and bacterial elicitors of community- and hospital-acquired pneumonia. Finally, we highlight the potential of EVs for improved management of pneumonia patients and discuss the translational steps to be taken before they can be safely exploited as novel vaccines, biomarkers, or therapeutics in clinical practice.

XANES studies on Eu-doped fluorozirconate based glass ceramics.

The influence of adding InF3 as a reducing agent on the oxidation state of Eu in fluorochloro- (FCZ) and fluorobromozirconate (FBZ) glass ceramics was investigated using x-ray absorption near edge (XANES) and photoluminescence (PL) spectroscopy. For both materials, it was found that InF3 decreases the Eu2+-to-Eu3+ ratio significantly. PL spectroscopy proved that an annealing step leads to the formation of Eu-doped BaCl2 and BaBr2 nanocrystals in the FCZ and FBZ glasses, respectively. In the case of FCZ glass ceramics the hexagonal phase of BaCl2 could be detected in indium-free and InF3-doped ceramics, but only for InF3 containing FCZ glass ceramics a phase transition of the nanoparticles from hexagonal to orthorhombic structure is observed. For the FBZ glass ceramics, the hexagonal phase of BaBr2 can be formed with and without indium doping, but only in the indium-free case a phase transition to orthorhombic BaBr2 could be found.