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White matter lesions (WMLs) are a common manifestation of small vessel disease (SVD) in the elderly population. They are associated with an enhanced risk of developing gait abnormalities, poor executive function, dementia, and stroke with high mortality. Hypoperfusion and the resulting endothelial damage are thought to contribute to the development of WMLs. The focus of the present study was the analysis of the microvascular bed in SVD patients with deep WMLs (DWMLs) by using double- and triple-label immunohistochemistry and immunofluorescence. Simultaneous visualization of collagen IV (COLL4)-positive membranes and the endothelial glycocalyx in thick sections allowed us to identify endothelial recession in different types of string vessels, and two new forms of small vessel/capillary pathology, which we called vascular bagging and ghost string vessels. Vascular bags were pouches and tubes that were attached to vessel walls and were formed by multiple layers of COLL4-positive membranes. Vascular bagging was most severe in the DWMLs of cases with pure SVD (no additional vascular brain injury, VBI). Quantification of vascular bagging, string vessels, and the density/size of CD68-positive cells further showed widespread pathological changes in the frontoparietal and/or temporal white matter in SVD, including pure SVD and SVD with VBI, as well as a significant effect of the covariate age. Plasma protein leakage into vascular bags and the white matter parenchyma pointed to endothelial damage and basement membrane permeability. Hypertrophic IBA1-positive microglial cells and CD68-positive macrophages were found in white matter areas covered with networks of ghost vessels in SVD, suggesting phagocytosis of remnants of string vessels. However, the overall vessel density was not altered in our SVD cohort, which might result from continuous replacement of vessels. Our findings support the view that SVD is a progressive and generalized disease process, in which endothelial damage and vascular bagging drive remodeling of the microvasculature.

The retinal vasculature supplies oxygen and nutrition to the cells and is crucial for an adequate retinal function. In myopia, excessive eye growth is associated with various anatomical changes that can lead to myopia-related complications. However, how myopia-induced ocular growth affects the integrity of the aged retinal microvasculature at the cellular level is not well understood. Here, we studied how aging interacts with myopia-induced alteration of the retinal microvasculature in fourteen marmoset retinas ( Callithrix jacchus ). String vessel and capillary branchpoint were imaged and quantified in all four capillary plexi of the retinal vasculature. As marmosets with lens-induced myopia aged, they developed increasing numbers of string vessels in all four vascular plexi, with increased vessel branchpoints in the parafoveal and peripapillary retina and decreased vessel branchpoints in the peripheral retina. These myopia-induced changes to the retinal microvasculature suggest an adaptive reorganization of the retinal microvascular cellular structure template with aging and during myopia development and progression.

The identification of cerebral microinfarctions with magnetic resonance imaging (MRI) and histological methods remains challenging in aging and dementia. Here, we matched pathological changes in the microvasculature of cortical cerebral microinfarcts to MRI signals using single 100 μm-thick histological sections scanned with ultra-high-resolution 11.7 T MRI. Histologically, microinfarcts were located in superficial or deep cortical layers or transcortically, compatible with the pattern of layer-specific arteriolar blood supply of the cerebral cortex. Contrary to acute microinfarcts, at chronic stages the core region of microinfarcts showed pallor with extracellular accumulation of lipofuscin and depletion of neurons, a dense meshwork of collagen 4-positive microvessels with numerous string vessels, CD68-positive macrophages and glial fibrillary acidic protein (GFAP)-positive astrocytes. In MRI scans, cortical microinfarcts at chronic stages, called chronic cortical microinfarcts here, gave hypointense signals in T1-weighted and hyperintense signals in T2-weighted images when thinning of the tissue and cavitation and/or prominent iron accumulation were present. Iron accumulation in chronic microinfarcts, histologically verified with Prussian blue staining, also produced strong hypointense T2*-weighted signals. In summary, the microinfarct core was occupied by a dense microvascular meshwork with string vessels, which was invaded by macrophages and astroglia and contained various degrees of iron accumulation. While postmortem ultra-high-resolution single-section imaging improved MRI-histological matching and the structural characterization of chronic cortical cerebral microinfarcts, miniscule microinfarcts without thinning or iron accumulation could not be detected with certainty in the MRI scans. Moreover, string vessels at the infarct margin indicate disturbances in the microcirculation in and around microinfarcts, which might be exploitable in the diagnostics of cortical cerebral microinfarcts with MRI in vivo.

Mesial temporal sclerosis (MTS) is the most common cause of drug-resistant temporal lobe epilepsy in adults. Despite nearly 2 centuries since the first reports of MTS, relatively little is known about its etiology and pathogenesis. Increasing attention has been directed toward the potential role of vascular abnormalities in MTS. We evaluated the hippocampal microvasculature in 9 MTS cases and 3 non-MTS controls using celloidin tissue sections and markers for total (collagen type IV) and afferent (enzymatic alkaline phosphatase) vessels. Tissue sections were assessed by light microscopy and quantified by threshold analysis of digital images and stereological analysis using the Space Balls probe. Although consistent alterations in the total microvascular density were not found, there was a significant reduction in the density of afferent vessels using both methodologies; these reductions were in areas CA2 and CA3 by image threshold analysis and in area CA3 using stereological measures of the ratio of afferent to total vessels. Increased numbers of string vessels (i.e. remnants of regressing vasculature) were also observed in Ammon's horn, suggesting vascular degeneration in the MTS hippocampus. These findings may help further our understanding of the pathophysiology of MTS.

Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (M pro ) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, M pro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood–brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the M pro -induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19. A novel study led by scientists in Lübeck, Germany, shows that SARS-CoV-2-infected brain endothelial cells undergo cell death due to the cleavage of NEMO by the viral protease M pro , potentially causing cerebral COVID-19 and ‘long COVID’ symptoms.

A bstract Oscura is a planned light-dark matter search experiment using Skipper-CCDs with a total active mass of 10 kg. As part of the detector development, the collaboration plans to build the Oscura Integration Test (OIT), an engineering test with 10% of the total mass. Here we discuss the early science opportunities with the OIT to search for millicharged particles (mCPs) using the NuMI beam at Fermilab. mCPs would be produced at low energies through photon-mediated processes from decays of scalar, pseudoscalar, and vector mesons, or direct Drell-Yan productions. Estimates show that the OIT would be a world-leading probe for mCPs in the ∼MeV mass range.

The internal thoracic artery is the choice of graft for coronary artery bypass grafting due to the excellent long-term patency. However internal thoracic artery graft failures still occur due to diffuse narrowing, known as the string phenomenon. Studies suggest that the string phenomenon is caused by competitive flow when the coronary stenosis is not serious, but the hemodynamics of the string phenomenon are still unclear. The purpose of this study is to clarify the hemodynamic characteristics of the string phenomenon. A patient-specific 3-dimensional model of the aortic arch and coronary arteries was reconstructed. A moderate stenosis was applied to the left anterior descending artery. The internal thoracic artery was used to bypass the stenosis. Two further 3D models were built to study the hemodynamics of the string phenomenon. A numerical study was performed by coupling the 3D artery model with 0-dimensional lumped parameter model of the cardiovascular system. The graft flow, native coronary flow, wall shear stress and oscillatory shear index were calculated and illustrated. Inverse flow and high oscillatory shear index appeared on the internal thoracic artery graft when the stenosis was moderate. High oscillatory shear index might be the major hemodynamic characteristic of the string phenomenon in internal thoracic artery graft. The inverse graft flow and the difference in graft flow caused by clamping the stenosis can be used to evaluate the probability of observing the string phenomenon.

Sandwich cylindrical structures are widely used in various industries, including high-speed trains, automotive, and civil engineering applications. To improve their performance, integrating polymeric foam cores and various configurations of periodic stiffeners into sandwich cylindrical shells significantly enhances their noise-cancellation capabilities. This paper investigates, for the first time, the acoustic parameters of sound transmission loss (STL) and noise reduction (NR) in an infinitely long sandwich cylindrical shell reinforced with annular and axial stiffeners (rings and strings), considering the effects of open-cell and closed-cell foams. The cross-sectional architecture consists of three layers: a functionally graded (FG) outer layer, an FG polymeric foam core, and an isotropic inner layer. Fluid (air) fills the gaps between the layers, and the shell is submerged in an external fluid medium while subjected to excitation by a plane acoustic wave. The outer and inner layers are further strengthened by circumferential and axial stiffeners. The polymeric foam core plays a crucial role in absorbing and dissipating sound energy, significantly enhancing the structure’s acoustic insulation properties. Meanwhile, the ring and string stiffeners improve overall mechanical stiffness, ensuring structural integrity and reducing vibrations. To address this problem, the motion equations of the shell are derived using the first-order shear deformation theory (FSDT) and Hamilton’s principle. The Zener viscoelastic model, which accounts for the frequency-dependent variation of material properties, is employed to model the viscoelastic core. The acoustic parameters are calculated by incorporating boundary conditions and fluid–structure interaction effects. Among the various reinforcement configurations, the highest STL and NR are achieved when both the inner and outer layers are reinforced, significantly improving vibration damping and acoustic insulation. When only the outer layer is reinforced, the structure performs better in the mass-controlled region, while reinforcing only the inner layer leads to superior performance in the stiffness-controlled region. Furthermore, open-cell foam outperforms closed-cell foam at higher frequencies due to its superior damping properties.

A bstract Charge Coupled Devices (CCD) are being used for reactor neutrino experiments and have already demonstrated their potential in constraining new physics models. The prospect of a Skipper-CCD experiment looking for standard and beyond standard model (BSM) physics in a nuclear reactor has been evaluated for different benchmark scenarios. Here, we report the first installation of a 2-g Skipper-CCD inside the containment building of a 2 GW th nuclear power plant and analyze its performance throughout its first 18 months of operation. The sensor was successfully deployed at Atucha II, in Argentina, 12 meters away from the center of the reactor core. We discuss the challenges involved in the commissioning of the detector and present data acquired during reactor ON and reactor OFF periods, with the sensor functioning with a sub-electron readout noise of 0.17 e − . Based on an exposure of 56.8 g day reactor ON and two reactor OFF data sets with a total exposure of 118.1 g day we characterize the system and evaluate the sensitivity to CEvNS. We achieved a background rate of 33 kdru and a low threshold of 45 eV ee . The ongoing efforts to improve sensitivities to CEvNS and BSM interaction are also discussed.

Background Coronary artery disease (CAD) is the leading cause of mortality worldwide. We aimed to screen out potential gene signatures and construct a diagnostic model for CAD. Method We downloaded two mRNA profiles, GSE66360 and GSE60993, and performed analyses of differential expression, gene ontology terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The STRING database was used to identify protein–protein interactions (PPI). PPI network visualization and screening out of key genes were performed using Cytoscape software. Finally, a diagnostic model was constructed. Results A total of 2127 differentially expressed genes (DEGs) were identified in GSE66360, and 527 DEGs in GSE60993. Of the 153 DEGs from both datasets that showed differential expression between CAD patients and controls, 471 biological process terms, 35 cellular component terms, 17 molecular function terms, and 49 KEGG pathways were significantly enriched. The top 20 key genes in the PPI network were identified, and a diagnostic model constructed from five optimal genes that could efficiently separate CAD patients from controls. Conclusion We identified several potential biomarkers for CAD and built a logistic regression model that will provide a valuable reference for future clinical diagnoses and guide therapeutic strategies.