Long-Term Antibody Response to SARS-CoV-2 in Children.

Almost 2 years into the pandemic and with vaccination of children significantly lagging behind adults, long-term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2.

Effect of ultraviolet photofunctionalization of dental titanium implants on osseointegration.

Objective: The aim of the current study was to evaluate the effect of ultraviolet (UV) photofunctionalization of dental titanium implants with exposure to the oral cavity on osseointegration in an animal model.

Methods: Forty-eight titanium implants (Camlog Conelog 4.3 mmx9.

Replication of Merkel cell polyomavirus induces reorganization of promyelocytic leukemia nuclear bodies.

Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare but aggressive skin cancer. The virus is highly prevalent: 60-80 % of adults are seropositive; however, cells permissive for MCPyV infection are unknown. Consequently, very little information about the MCPyV life cycle is available.

In Vitro Replication Assay for Merkel Cell Polyomavirus (MCPyV).

Merkel cell polyomavirus (MCPyV) genomes are clonally integrated in tumor cells of ∼95% of all Merkel cell carcinoma (MCC) cases. The virus is highly prevalent; however, where the virus persists and which cell types are permissive for MCPyV replication is still unknown. As a consequence, very little information is available about the life cycle and no fully permissive in vitro replication system has been established.

A Comprehensive Analysis of Replicating Merkel Cell Polyomavirus Genomes Delineates the Viral Transcription Program and Suggests a Role for mcv-miR-M1 in Episomal Persistence.

Merkel cell polyomavirus (MCPyV) is considered the etiological agent of Merkel cell carcinoma and persists asymptomatically in the majority of its healthy hosts. Largely due to the lack of appropriate model systems, the mechanisms of viral replication and MCPyV persistence remain poorly understood. Using a semi-permissive replication system, we here report a comprehensive analysis of the role of the MCPyV-encoded microRNA (miRNA) mcv-miR-M1 during short and long-term replication of authentic MCPyV episomes.

MTSS1 is a metastasis driver in a subset of human melanomas.

In cancers with a highly altered genome, distinct genetic alterations drive subsets rather than the majority of individual tumours. Here we use a sequential search across human tumour samples for transcript outlier data points with associated gene copy number variations that correlate with patient's survival to identify genes with pro-invasive functionality. Employing loss and gain of function approaches in vitro and in vivo, we show that one such gene, MTSS1, promotes the ability of melanocytic cells to metastasize and engages actin dynamics via Rho-GTPases and cofilin in this process.

High-affinity Rb binding, p53 inhibition, subcellular localization, and transformation by wild-type or tumor-derived shortened Merkel cell polyomavirus large T antigens.

Unlabelled: Interference with tumor suppressor pathways by polyomavirus-encoded tumor antigens (T-Ags) can result in transformation. Consequently, it is thought that T-Ags encoded by Merkel cell polyomavirus (MCPyV), a virus integrated in ∼90% of all Merkel cell carcinoma (MCC) cases, are major contributors to tumorigenesis. The MCPyV large T-Ag (LT-Ag) has preserved the key functional domains present in all family members but has also acquired unique regions that flank the LxCxE motif.

An attempt at a molecular prediction of metastasis in patients with primary cutaneous melanoma.

Background: Current prognostic clinical and morphological parameters are insufficient to accurately predict metastasis in individual melanoma patients. Several studies have described gene expression signatures to predict survival or metastasis of primary melanoma patients, however the reproducibility among these studies is disappointingly low.

Methodology/principal Findings: We followed extended REMARK/Gould Rothberg criteria to identify gene sets predictive for metastasis in patients with primary cutaneous melanoma.

Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.

Merkel Cell Polyomavirus (MCPyV) genomes are clonally integrated in tumor tissues of approximately 85% of all Merkel cell carcinoma (MCC) cases, a highly aggressive tumor of the skin which predominantly afflicts elderly and immunosuppressed patients. All integrated viral genomes recovered from MCC tissue or MCC cell lines harbor signature mutations in the early gene transcript encoding for the large T-Antigen (LT-Ag). These mutations selectively abrogate the ability of LT-Ag to support viral replication while still maintaining its Rb-binding activity, suggesting a continuous requirement for LT-Ag mediated cell cycle deregulation during MCC pathogenesis.

Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier.

We attempted to assess regional differences in cerebral P-glycoprotein (P-gp) function by performing paired positron emission tomography (PET) scans with the P-gp substrate (R)-[(11)C]verapamil in five healthy subjects before and after i.v. infusion of tariquidar (2 mg/kg).

Methods from the theory of random heterogeneous media for quantifying myocardial morphology in normal and dilated hearts.

In the present study, descriptors from the theory of random heterogeneous media were used to characterize the morphology of the myocardial interstitial space in histological sections from hearts of healthy subjects and of patients with idiopathic dilated cardiomyopathy (DCM). Histological sections from resected DCM hearts (n = 9) were compared with donor hearts showing no signs of cardiac disease (n = 6). From control to DCM, the area fraction phi(1) of the interstitial space increased from 0.

Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET.

Purpose: The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier.

Methods: Seven young (mean age: 27 +/- 4 years) and six elderly (mean age: 69 +/- 9 years) healthy volunteers underwent dynamic (R)-[(11)C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM).

[Different attitudes towards hypertension and urinary tract incontinence in elderly individuals participating in a health promotion project].

Background: The aim of the study was to evaluate health associated attitudes of elderly individuals taking part in a community based health promotion programme. It was of interest to focus on mobility, hypertension and urinary incontinence, problems frequently observed in geriatrics.

Methods: Participants in the health promotion programme were asked to answer a standardized questionnaire about their individual risk factors and habits concerning some of the main risk factors in the elderly: social isolation, immobility, hypertension, urinary incontinence.

Error estimation of geometrical data obtained by histomorphometry of oblique vessel sections: a computer model study.

The errors of radius and wall thickness of a single vessel due to oblique sectioning in histomorphometry are expressed as a function of the circular shape factor (CSF) of the section's lumen, assuming cylindrical geometry and the absence of tissue deformation. Using computer model trees generated by constrained constructive optimization, mean errors are estimated for an ensemble of vessel segments. A geometrical exclusion criterion for segments cut too obliquely is defined on the basis of a CSF-cutoff value.

Optimized arterial trees supplying hollow organs.

Computer models of arterial trees can be generated from optimization principles using the algorithm of constrained constructive optimization (CCO). Up to now this algorithm could handle only tissue areas of convex shape, without concavities. CCO is now generalized to cope also with non-convex organ shapes, possibly featuring external as well as internal concavities.

The spatial pattern of coronary capillaries in patients with dilated, ischemic, or inflammatory cardiomyopathy.

Introduction: The goal of the present study was to compare the pattern of coronary capillaries in healthy participants and in patients with end-stage heart failure due to idiopathic dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), or inflammatory cardiomyopathy (InfCM).

Methods: Capillary patterns were studied in histological sections from resected hearts from patients with DCM (n=5), ICM (n=5), or InfCM (n=5) and compared with donor hearts showing no signs of cardiac disease (n=3). Patterns were characterized by the distribution of Voronoi polygon areas, A, associated with the centers of capillary profiles, nearest-neighbor distances, d, intercapillary distances (ICD), as well as by means of the pair correlation function g(r).

Fractal properties of perfusion heterogeneity in optimized arterial trees: a model study.

Regional blood flows in the heart muscle are remarkably heterogeneous. It is very likely that the most important factor for this heterogeneity is the metabolic need of the tissue rather than flow dispersion by the branching network of the coronary vasculature. To model the contribution of tissue needs to the observed flow heterogeneities we use arterial trees generated on the computer by constrained constructive optimization.

Voronoi polyhedra analysis of optimized arterial tree models.

Topological and metric properties of Voronoi polyhedra (VP) generated by the distal end points of terminal segments in arterial tree models grown by the method of constrained constructive optimization (CCO) are analyzed with the aim to characterize the spatial distribution of their supply sites relative to randomly distributed points as a reference model. The distributions of the number Nf of Voronoi cell faces, cell volume V, surface area S, area A of individual cell faces, and asphericity parameter alpha of the CCO models are all significantly different from the ones of random points, whereas the distributions of V, S, and alpha are also significantly different among CCO models optimized for minimum intravascular volume and minimum segment length (p < 0.0001).

Heterogeneous perfusion is a consequence of uniform shear stress in optimized arterial tree models.

Using optimized computer models of arterial trees we demonstrate that flow heterogeneity is a necessary consequence of a uniform shear stress distribution. Model trees are generated and optimized under different modes of boundary conditions. In one mode flow is delivered to the tissue as homogeneously as possible.