Alzheimer\'s disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid β (Aβ)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aβ amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aβ in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.

Most acute coronary syndromes are due to a sudden luminal embolism caused by the rupturing or erosion of atherosclerotic plaques. Prevention and treatment of plaque development have become an effective strategy to reduce mortality and morbidity from coronary heart disease. It is now generally accepted that plaques with thin-cap fibroatheroma (TCFA) are precursors to rupturing and that larger plaques and high-risk plaque features (including low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification) constitute unstable plaque morphologies. However, plaque vulnerability or rupturing is a complex evolutionary process caused by a combination of multiple factors. Using a combination of medicine, engineering mechanics, and computer software, researchers have turned their attention to computational fluid mechanics. The importance of fluid mechanics in pathological states for promoting plaque progression, inducing plaque tendency to vulnerability, or even rupture, as well as the high value of functional evaluation of myocardial ischemia has become a new area of research. This article reviews recent research advances in coronary plaque fluid mechanics, aiming to describe the concept, research implications, current status of clinical studies, and limitations of fluid mechanic\'s characteristic parameters: wall shear stress (WSS), axial plaque shear (APS), and fractional flow reserve (FFR). Previously, most computational fluid dynamics were obtained using invasive methods, such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT). In recent years, the image quality and spatial resolution of coronary computed tomography angiography (CCTA) have greatly improved, making it possible to compute fluid dynamics by noninvasive methods. In the future, the combination of CCTA-based anatomical stenosis, plaque high-risk features, and fluid mechanics can further improve the prediction of plaque development, vulnerability, and risk of rupturing, as well as enabling noninvasive means to assess the degree of myocardial ischemia, thereby providing an important aid to guide clinical decision-making and optimize treatment.

Recent advances in immunotherapeutic approaches to the treatment of Alzheimer\'s disease (AD) have increased the importance of understanding the exact binding preference of each amyloid-beta (Aβ) antibody employed, since this determines both efficacy and risk for potentially serious adverse events known as amyloid-related imaging abnormalities. Lecanemab is a humanized IgG1 antibody that was developed to target the soluble Aβ protofibril conformation. The present study prepared extracts of post mortem brain samples from AD patients and non-demented elderly controls, characterized the forms of Aβ present, and investigated their interactions with lecanemab. Brain tissue samples were homogenized and extracted using tris-buffered saline. Aβ levels and aggregation states in soluble and insoluble extracts, and in fractions prepared using size-exclusion chromatography or density gradient ultracentrifugation, were analyzed using combinations of immunoassay, immunoprecipitation (IP), and mass spectrometry. Lecanemab immunohistochemistry was also conducted in temporal cortex. The majority of temporal cortex Aβ (98 %) was in the insoluble extract. Aβ42 was the most abundant form present, particularly in AD subjects, and most soluble Aβ42 was in soluble aggregated protofibrillar structures. Aβ protofibril levels were much higher in AD subjects than in controls. Protofibrils captured by lecanemab-IP contained high levels of Aβ42 and lecanemab bound to large, medium, and small Aβ42 protofibrils in a concentration-dependent manner. Competitive IP showed that neither Aβ40 monomers nor Aβ40-enriched fibrils isolated from cerebral amyloid angiopathy reduced lecanemab\'s binding to Aβ42 protofibrils. Immunohistochemistry showed that lecanemab bound readily to Aβ plaques (diffuse and compact) and to intraneuronal Aβ in AD temporal cortex. Taken together, these findings indicate that while lecanemab binds to Aβ plaques, it preferentially targets soluble aggregated Aβ protofibrils. These are largely composed of Aβ42, and lecanemab binds less readily to the Aβ40-enriched fibrils found in the cerebral vasculature. This is a promising binding profile because Aβ42 protofibrils represent a key therapeutic target in AD, while a lack of binding to monomeric Aβ and cerebral amyloid deposits should reduce peripheral antibody sequestration and minimize risk for adverse events.

With the enormous progress in the field of cardiovascular imaging in recent years, computed tomography (CT) has become readily available to phenotype atherosclerotic coronary artery disease. New analytical methods using artificial intelligence (AI) enable the analysis of complex phenotypic information of atherosclerotic plaques. In particular, deep learning-based approaches using convolutional neural networks (CNNs) facilitate tasks such as lesion detection, segmentation, and classification. New radiotranscriptomic techniques even capture underlying bio-histochemical processes through higher-order structural analysis of voxels on CT images. In the near future, the international large-scale Oxford Risk Factors And Non-invasive Imaging (ORFAN) study will provide a powerful platform for testing and validating prognostic AI-based models. The goal is the transition of these new approaches from research settings into a clinical workflow. In this review, we present an overview of existing AI-based techniques with focus on imaging biomarkers to determine the degree of coronary inflammation, coronary plaques, and the associated risk. Further, current limitations using AI-based approaches as well as the priorities to address these challenges will be discussed. This will pave the way for an AI-enabled risk assessment tool to detect vulnerable atherosclerotic plaques and to guide treatment strategies for patients.

BACKGROUND: Antiretroviral therapy has allowed a clear improvement in prognosis for HIV patients, but metabolic problems, such as dyslipidemia, remain. This can lead to the development of atheromatous plaques. Our study aims to evaluate whether HIV-positive (HIV+) patients show higher myo-intimal media thickness (IMT) and atheromatous plaques compared to HIV-negative (HIV-) patients.
METHODS: To evaluate the association between HIV infection in experienced patients and vascular pathology, we performed a cross-sectional study, observing 1006 patients, 380 HIV+ enrolled in the Archiprevaleat cohort, and 626 HIV- as a control group. All patients underwent a Doppler scan of the supra-aortic vessels. We compared the prevalence of IMT > 1.0 mm and plaques in the two groups.
RESULTS: Patients in the HIV+ group were younger than those in the HIV- group, with a lower prevalence of hypertension and diabetes and higher dyslipidemia. The prevalence of plaques in strata of age was higher in the HIV+ group than in the HIV- group and was associated with the length of ART exposure.
CONCLUSIONS: Our cross-sectional, retrospective study shows that HIV+ experienced patients are at greater risk of IMT and atheromatous plaques compared to HIV-. The risk is associated with being HIV+ and with the length of ART exposure. This finding may be useful in preventing cardiovascular risk.

BACKGROUND: When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease.
OBJECTIVE: The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods.
METHODS: Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented.
RESULTS: Assessing asbestos-related diseases requires recognition of the person\'s occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM).
CONCLUSIONS: The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients\' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains a concern.
UNASSIGNED: HINTERGRUND: Werden Asbestfasern eingeatmet, können sich in der Lunge sog. Asbestkörperchen unter Beteiligung von Makrophagen ausbilden. Von der letzten Exposition bis zum Ausbrechen einer asbestbedingten Erkrankung können Jahrzehnte vergehen.
UNASSIGNED: Das Ziel dieser Übersichtsarbeit ist die Darstellung der Nachweismöglichkeiten von Asbest im Lungengewebe, die Entwicklung der Diagnosekriterien und die Diskussion der Vor- und Nachteile unterschiedlicher Methoden.
METHODS: Es werden Beobachtungen und Auswertungen des Deutschen Mesotheliomregisters unter Hinzuziehung und Auswertung relevanter Fachliteratur sowie Expertenempfehlungen in Leitlinien betrachtet.
UNASSIGNED: Für die Beurteilung einer asbestbedingten Erkrankung sind neben der Erfassung der persönlichen arbeitsbedingten Exposition, die Quantifizierung der inhalierten Fasern und die Bestimmung des Fasertyps von Bedeutung. Hierbei sind verschiedene Methoden entwickelt und validiert worden. Es finden lichtmikroskopische und/oder elektronenmikroskopische Untersuchungen Anwendung wie die Hellfeldmikroskopie, Phasenkontrastmikroskopie, Polarisationsmikroskopie und Differenzialinterferenzmikroskopie, sowie elektronenmikroskopisch die Rasterelektronenmikroskopie (z. B. Feldemissionsrasterelektronenmikroskop, FE-REM) und Transmissionselektronenmikroskopie (TEM).
UNASSIGNED: Die Verwendung von Asbest wurde weltweit stark eingeschränkt, in Europa sogar vollständig verboten. Somit nimmt die Exposition der Patienten gegenüber Asbest ab. In den Vordergrund rücken Asbestexpositionen bei Sanierungen und Rückbauten oder durch den unbewussten Umgang mit asbesthaltigen Materialien.

BACKGROUND: A plethora of studies has shown the utility of several chemical dyes due to their affinity to bind Aβ to enable visualization of plaques under light or fluorescence microscope, and some of them showed affinity to bind neurofibrillary tangles (NFT) as well. However, only a few of them have the propensity to bind both senile plaques (SP) and NFT simultaneously.
OBJECTIVE: In our current study, we aimed to modify the K114 dye and the staining procedure to substantially improve the staining of amyloid plaques in both human and rodent brains and neurofibrillary tangles in the human brain.
METHODS: We modified the K114 solution and the staining procedure using Sudan Black as a modifier. Additionally, to evaluate the target of the modified K114, we performed double labeling of K114 and increased Aβ against three different epitopes. We used 5 different antibodies to detect phosphorylated tau to understand the specific targets that modified K114 binds.
RESULTS: Dual labeling using hyperphosphorylated antibodies against AT8, pTau, and TNT1 revealed that more than 80% hyperphosphorylated tau colocalized with tangles that were positive for modified K114, whereas more than 70% of the hyperphosphorylated tau colocalized with modified K114. On the other hand, more than 80% of the plaques that were stained with Aβ MOAB-2 were colocalized with modified K114.
CONCLUSIONS: Our modified method can label amyloid plaques within 5 min in the rat brain and within 20 min in the human brain. Our results indicated that modified K114 could be used as a valuable tool for detecting amyloid plaques and tangles with high contrast and resolution relative to other conventional fluorescence markers.

Bacteriophages are ubiquitous biological entities which can be found in a variety of habitats. Here, we describe protocols for the isolation of bacteriophages on a variety of Actinobacterial genera. Two approaches to phage isolation, direct isolation and enriched isolation, are described, which can be performed individually or in parallel. The protocols described can be adapted to isolate a wide array of bacteriophages.

Atherosclerosis, which currently contributes to 31% of deaths globally, is of critical cardiovascular concern. Current diagnostic tools and biomarkers are limited, emphasizing the need for early detection. Lifestyle modifications and medications form the basis of treatment, and emerging therapies such as photodynamic therapy are being developed. Photodynamic therapy involves a photosensitizer selectively targeting components of atherosclerotic plaques. When activated by specific light wavelengths, it induces localized oxidative stress aiming to stabilize plaques and reduce inflammation. The key advantage lies in its selective targeting, sparing healthy tissues. While preclinical studies are encouraging, ongoing research and clinical trials are crucial for optimizing protocols and ensuring long-term safety and efficacy. The potential combination with other therapies makes photodynamic therapy a versatile and promising avenue for addressing atherosclerosis and associated cardiovascular disease. The investigations underscore the possibility of utilizing photodynamic therapy as a valuable treatment choice for atherosclerosis. As advancements in research continue, photodynamic therapy might become more seamlessly incorporated into clinical approaches for managing atherosclerosis, providing a blend of efficacy and limited invasiveness.

Brain-derived extracellular vesicles (EVs) play an active role in Alzheimer\'s disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making EVs attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease-vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF ) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labelling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40-150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g., APPswe, PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with Aβ deposition. Genotype, age, and Aβ deposition modulated proteostasis- and immunometabolic-related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust- and diverse- EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD.