Universal behavior of the IMS domain formation in superconducting niobium

In the intermediate mixed state (IMS) of type-II/1 superconductors, vortex lattice (VL) and Meissner state domains coexist due to a partially attractive vortex interaction. Using a neutron-based multiscale approach combined with magnetization measurements, we study the continuous decomposition of a homogeneous VL into increasingly dense domains in the IMS in bulk niobium samples of varying purity. We find a universal temperature dependence of the vortex spacing, closely related to the London penetration depth and independent of the external magnetic field. The rearrangement of vortices occurs even in the presence of a flux freezing transition, i.e. pronounced pinning, indicating a breakdown of pinning at the onset of the vortex attraction

Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes

Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes.Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-β2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression.The exosomes were rounded in shape and had an average size of 50–90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-β2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups.We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system. To access the supplementary material to this article, please see Supplementary files under Article Tools online

RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to Disturbed Calcium Handling

BACKGROUND: Mutations in RBM20 (RNA-binding motif protein 20) cause a clinically aggressive form of dilated cardiomyopathy, with an increased risk of malignant ventricular arrhythmias. RBM20 is a splicing factor that targets multiple pivotal cardiac genes, such as Titin (TTN) and CAMK2D (calcium/calmodulin-dependent kinase II delta). Aberrant TTN splicing is thought to be the main determinant of RBM20-induced dilated cardiomyopathy, but is not likely to explain the increased risk of arrhythmias. Here, we investigated the extent to which RBM20 mutation carriers have an increased risk of arrhythmias and explore the underlying molecular mechanism

Reliability and Validity of the Multidimensional Scale of Perceived Social Support (MSPSS): Thai Version

This study examines the Thai version of the Multidimensional Scale of Perceived Social Support (MSPSS) for its psychometric properties

Heart rate variability (HRV) and muscular system activity (EMG) in cases of crash threat during simulated driving of a passenger car

Objectives: The aim of the study was to verify whether simultaneous responses from the muscular and circulatory system occur in the driver's body under simulated conditions of a crash threat. Materials and Methods: The study was carried out in a passenger car driving simulator. The crash was included in the driving test scenario developed in an urban setting. In the group of 22 young male subjects, two physiological signals - ECG and EMG were continuously recorded. The length of the RR interval in the ECG signal was assessed. A HRV analysis was performed in the time and frequency domains for 1-minute record segments at rest (seated position), during undisturbed driving as well as during and several minutes after the crash. For the left and right side muscles: m. trapezius (TR) and m. flexor digitorum superficialis (FDS), the EMG signal amplitude was determined. The percentage of maximal voluntary contraction (MVC) was compared during driving and during the crash. Results: As for the ECG signal, it was found that in most of the drivers changes occurred in the parameter values reflecting HRV in the time domain. Significant changes were noted in the mean length of RR intervals (mRR). As for the EMG signal, the changes in the amplitude concerned the signal recorded from the FDS muscle. The changes in ECG and EMG were simultaneous in half of the cases. Conclusion: Such parameters as mRR (ECG signal) and FDS-L amplitude (EMG signal) were the responses to accident risk. Under simulated conditions, responses from the circulatory and musculoskeletal systems are not always simultaneous. The results indicate that a more complete driver's response to a crash in road traffic is obtained based on parallel recording of two physiological signals (ECG and EMG)

A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function

\ua9 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF

Do general practitioners and psychiatrists agree about defining cure from depression? The DEsCRIBE™ survey

BACKGROUND: This study aimed to document the outcome dimensions that physicians see as important in defining cure from depression. The study also aimed to analyse physicians' attitudes about depression and to find out whether they affect their prescribing practices and/or the outcome dimensions that they view as important in defining cure. METHODS: A 51-item questionnaire based on six validated scales was used to rate the importance of several depression outcome dimensions. Physicians' attitudes about depression were also assessed using the Depression Attitude Scale. Overall, 369 Belgian physicians (264 general practitioners [GPs]; 105 psychiatrists) participated in the DEsCRIBE survey. RESULTS: GPs and psychiatrists strongly agreed that functioning and depressive symptomatology were most important in defining cure; anxious and somatic symptomatology was least important. GPs and psychiatrists differed in their attitudes about depression (p <0.001). Logistic regression revealed that the attitudes of GPs - but not psychiatrists - were significantly associated with their rates of antidepressant prescription (p < 0.001) and that certain attitudes predicted which outcome dimensions were seen as important in defining cure. CONCLUSIONS: Belgian GPs and psychiatrists strongly agreed on which criteria were important in defining cure from depression but differed in their attitudes about depression. The outcome dimensions that were considered important in defining cure were influenced by physicians' attitudes - this was more pronounced in GPs than in psychiatrists

Extent and patterns of community collaboration in local health departments: An exploratory survey

<p>Abstract</p> <p>Background</p> <p>Local public health departments (LHDs) in the United States have been encouraged to collaborate with various other community organizations and individuals. Current research suggests that many forms of active partnering are ongoing, and there are numerous examples of LHD collaboration with a specific organization for a specific purpose or program. However, no existing research has attempted to characterize collaboration, for the defined purpose of setting community health status priorities, between a defined population of local officials and a defined group of alternative partnering organizations. The specific aims of this study were to 1) determine the range of collaborative involvement exhibited by a study population of local public health officials, and, 2) characterize the patterns of the selection of organizations/individuals involved with LHDs in the process of setting community health status priorities.</p> <p>Methods</p> <p>Local health department officials in North Carolina (n = 53) responded to an exploratory survey about their levels of involvement with eight types of possible collaborator organizations and individuals. Descriptive statistics and the stochastic clustering technique of Self-Organizing Maps (SOM) were used to characterize their collaboration.</p> <p>Results</p> <p>Local health officials vary extensively in their level of collaboration with external collaborators. While the range of total involvement varies, the patterns of involvement for this specific function are relatively uniform. That is, regardless of the total level of involvement (low, medium or high), officials maintain similar hierarchical preference rankings with Community Advisory Boards and Local Boards of Health most involved and Experts and Elected Officials least involved.</p> <p>Conclusion</p> <p>The extent and patterns of collaboration among LHDs with other community stakeholders for a specific function can be described and ultimately related to outcome measures of LHD performance.</p

Inflammation leads through PGE/EP3 signaling to HDAC5/MEF2-dependent transcription in cardiac myocytes

The myocyte enhancer factor 2 (MEF2) regulates transcription in cardiac myocytes and adverse remodeling of adult hearts. Activators of G protein-coupled receptors (GPCRs) have been reported to activate MEF2, but a comprehensive analysis of GPCR activators that regulate MEF2 has to our knowledge not been performed. Here, we tested several GPCR agonists regarding their ability to activate a MEF2 reporter in neonatal rat ventricular myocytes. The inflammatory mediator prostaglandin E2 (PGE2) strongly activated MEF2. Using pharmacological and protein-based inhibitors, we demonstrated that PGE2 regulates MEF2 via the EP3 receptor, the betagamma subunit of Gi/o protein and two concomitantly activated downstream pathways. The first consists of Tiam1, Rac1, and its effector p21-activated kinase 2, the second of protein kinase D. Both pathways converge on and inactivate histone deacetylase 5 (HDAC5) and thereby de-repress MEF2. In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies