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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. Summary 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.

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. Dsuoa2jziZXJVhhK23tmJq Video Abstract

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. 7FMb6rvPxRFWumGrBQKEMq Video Abstract

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.

This chapter gives an overview of the concept of fluorescent concentrators, including the theory, materials for the realization of fluorescent collectors, and the characterization of fluorescent concentrator systems with attached solar cells. It shows that fundamental aspects, such as efficiency limits, can be investigated using an elegant and detailed balance approach. One major finding, both from theory and experimental results, is that spectrally selectively reflecting structures can increase the efficiency of fluorescent concentrators systems significantly. Fluorescent concentrator systems with III‐V solar cells mounted on the edge of fluorescent collectors have shown the highest efficiencies. The chapter also demonstrates that the power output of a GaInP can be increased by a factor of 3.7 if it is attached to a fluorescent collector. Nevertheless, also for other types of solar cells out of amorphous or c‐Si, fluorescent collectors can increase the power output by harvesting light from a larger area.

Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are required to validate candidates in high throughput and at low cost. Here, we established a cell-free protein synthesis (CFPS) pipeline for the rapid and inexpensive production of antimicrobial peptides (AMPs) directly from DNA templates. To validate our platform, we used deep learning to design thousands of AMPs de novo. Using computational methods, we prioritized 500 candidates that we produced and screened with our CFPS pipeline. We identified 30 functional AMPs, which we characterized further through molecular dynamics simulations, antimicrobial activity and toxicity. Notably, six de novo-AMPs feature broad-spectrum activity against multidrug-resistant pathogens and do not develop bacterial resistance. Our work demonstrates the potential of CFPS for production and testing of bioactive peptides within less than 24 hours and <10$ per screen.Competing Interest StatementThe authors have declared no competing interest.

Young children's early experiences with language, print, and story-structure facilitate their understanding of reading. Parents are most frequently the people in the pre-schooler's environment providing the child with bookreading experience. The beliefs and assumptions that the parent brings to joint bookreading will influence the language he or she uses, which features of the story and/or pictures are emphasized, and the questions posed to the child during literacy events. Therefore, the purpose of this investigation was to describe the different kinds of support parents provide for their children during reading and explored the ways in which parents' beliefs about literacy acquisition influenced the interactions they provided for their children. Questions that guided this investigation were: (a) What beliefs do parents hold regarding the nature of oral language and literacy development? (b) What do parents believe regarding their child's ability to engage in literacy events? and (c) During literacy events, which scaffolding behaviors are provided by parents? The literacy theories of four parent participants were described by analyzing pre- and post-interviews. Four observations of parents reading to their children were conducted. Specific scaffolding behaviors such as parent statements and questions used during joint bookreading were described and analyzed in terms of parent assumptions regarding literacy. The literacy theories of the four participants shared a number of commonalities. They believed in (a) reading frequently with their children, (b) reading and language development informing and supporting one another, and (c) accessing prior knowledge, linguistic knowledge, and schema to aid meaning-making. Subtle shifts in scaffolding behaviors were noted in relation to the parents' specific assumptions about reading and parents' classifications of their children's abilities. Instructional implications point to the need to understand and work with each parent's theory of reading, rather than merely offering a list of suggestions for parents.

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a recent class of anti-HBV antivirals. CAMs disturb proper nucleocapsid assembly, by inducing formation of either aberrant assemblies (CAM-A) or of apparently normal but genome-less empty capsids (CAM-E). Classical structural approaches have revealed the CAM binding sites on the capsid protein (Cp), but conformational information on the CAM-induced off-path aberrant assemblies is lacking. Here we show that solid-state NMR can provide such information, including for wild-type full-length Cp183, and we find that in these assemblies, the asymmetric unit comprises a single Cp molecule rather than the four quasi-equivalent conformers typical for the icosahedral T = 4 symmetry of the normal HBV capsids. Furthermore, while in contrast to truncated Cp149, full-length Cp183 assemblies appear, on the mesoscopic level, unaffected by CAM-A, NMR reveals that on the molecular level, Cp183 assemblies are equally aberrant. Finally, we use a eukaryotic cell-free system to reveal how CAMs modulate capsid-RNA interactions and capsid phosphorylation. Our results establish a structural view on assembly modulation of the HBV capsid, and they provide a rationale for recently observed differences between in-cell versus in vitro capsid assembly modulation. Hepatitis B virus (HBV) capsid assembly modulators (CAM) represent a recent class of anti-HBV antivirals. Structural approaches provide limited conformational information on the CAM-induced off-path assemblies. Here, authors use solid-state NMR to establish a structural view on assembly modulation of the HBV capsid.

Background Empirical evidence shows that 4.6–6.3% of all women develop a post-traumatic stress disorder (PTSD) and approximately 10–15% postpartum depression (PPD) following childbirth. This study explores the relationship between delivery mode and the occurrence of PTSD and PPD, specifically examining four distinct caesarean section (CS) modes: primary on maternal request (Grade 4), medically indicated primary (Grade 3), secondary CS from relative indication (Grade 2) and emergency secondary CS (Grade 1), compared to vaginal and assisted vaginal delivery (AVD). The research aims to understand how these six subcategories of delivery modes impact PPD and PTSD levels. Common predictors, including the need for psychological treatment before childbirth, fear of childbirth, planning of pregnancy, induction of labor, birth debriefing, and lack of social support after childbirth, will be analyzed to determine their association with postpartum mental health outcomes. Methods The study was planned and carried out by a research team of the psychology department at the Medical School Hamburg, Germany. Within an online-study (cross-sectional design) N  = 1223 German speaking women with a baby who did not die before, during or after birth were surveyed once between four weeks and twelve months postpartum via an anonymous online questionnaire on demographic and gynecological data, delivery mode, PTSD (PCL-5) and PPD (EPDS). Results For both psychiatric disorders, ANOVA revealed significant differences between delivery mode and PPD and PTSD. With weak effects for PPD and medium to strong effects for PTSD. Post-hoc tests showed increased levels of PPD for two CS types (Grade 1, Grade 3) compared to vaginal delivery. For PTSD, secondary CS from relative indication (Grade 2), emergency secondary CS (Grade 1) and assisted vaginal delivery (AVD) were associated with elevated levels of PTSD. Regression analysis revealed delivery mode as a significant predictor of EPDS- (medium effect size) and PCL-5-Score (medium to high effect size). Limitation Delivery was considered as the potential traumatic event, and any previous traumas were not documented. Additionally, the categorization of delivery modes relied on subjective reports rather than medical confirmation. Conclusion The study highlights the influence of delivery mode on the mental health of postpartum mothers: different modes influence postpartum disorders in various ways. However, the definition of delivery mode was only stated subjectively and not medically confirmed. Further research should investigate which aspects of the different delivery modes affect maternal mental health and explore how the perception of childbirth may be influenced by specific delivery experiences.

Progress in NMR in general and in biomolecular applications in particular is driven by increasing magnetic-field strengths leading to improved resolution and sensitivity of the NMR spectra. Recently, persistent superconducting magnets at a magnetic field strength (magnetic induction) of 28.2 T corresponding to 1200 MHz proton resonance frequency became commercially available. We present here a collection of high-field NMR spectra of a variety of proteins, including molecular machines, membrane proteins, viral capsids, fibrils and large molecular assemblies. We show this large panel in order to provide an overview over a range of representative systems under study, rather than a single best performing model system. We discuss both carbon-13 and proton-detected experiments, and show that in 13C spectra substantially higher numbers of peaks can be resolved compared to 850 MHz while for 1H spectra the most impressive increase in resolution is observed for aliphatic side-chain resonances.