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Chronic Inflammation and Atherosclerosis

Inflammation is a vital response and necessary for maintaining homeostasis. Inflammation protects against tissue damage and pathogens-but is also one of the main driving forces of the atherosclerotic plaque progression. How and why the inflammatory response is initiated in the atherosclerotic disease is not fully known, but evidence suggests modified lipids as potential antigens activating the imm

The chronic stress risk phenotype mirrored in the human retina as a neurodegenerative condition

The brain is the key organ that orchestrates the stress response which translates to the retina. The retina is an extension of the brain and retinal symptoms in subjects with neurodegenerative diseases substantiated the eye as a window to the brain. The retina is used in this study to determine whether chronic stress reflects neurodegenerative signs indicative of neurodegenerative conditions. A 3-

Fluorescence microscopy studies of interactions between monomeric α-Synuclein and lipid membranes

α-Synuclein (α-Syn), is an intrinsically disordered protein present in the substantia nigra part of the brain. α-Syn is commonly known to associate with lipid membranes containing anionic lipids. Hence, the protein is hypothesized to be involved in the vesicle trafficking at the synapses, but there are yet many unanswered questions regarding the full physiological role of the protein. During the d

Photo-Induced Cross-Linking of Unmodified α-Synuclein Oligomers

Photo-induced cross-linking of unmodified proteins (PICUP) has been used in the past to study size distributions of protein assemblies. PICUP may, for example, overcome the significant experimental challenges related to the transient nature, heterogeneity, and low concentration of amyloid protein oligomers relative to monomeric and fibrillar species. In the current study, a reaction chamber was de

A randomized trial involving a multifunctional diet reveals systematic lipid remodeling and improvements in cardiometabolic risk factors in middle aged to aged adults

BACKGROUND: A multifunctional diet (MFD) combining foods and ingredients with proven functional properties, such as fatty fish and fiber-rich foods, among others, was developed and shown to markedly reduce cardiometabolic risk-associated factors.OBJECTIVE: Here, we aim at examining metabolic physiological changes associated with these improvements.METHODS: Adult overweight individuals without othe

3D analysis and grading of calcifications from ex vivo human meniscus

Objective: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (μCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. Method: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (

Assessing the importance of predictors of adherence to a digital self‑management intervention for osteoarthritis

OBJECTIVE: Treatment adherence is suggested to be associated with greater improvement in patient outcomes. Despite the growing use of digital therapeutics in osteoarthritis management, there is limited evidence of person-level factors influencing adherence to these interventions in real-world settings. We aimed to determine the relative importance of factors influencing adherence to a digital self

Protocol for optical clearing and imaging of fluorescently labeled ex vivo rat brain slices

Tissue clearing is commonly used for whole-brain imaging but seldom used for brain slices. Here, we present a simple protocol to slice, immunostain, and clear sections of adult rat brains for subsequent high-resolution confocal imaging. The protocol does not require toxic reagents or specialized equipment. We also provide instructions for culturing of rat brain slices free floating on permeable cu

Does lower educational attainment increase the risk of osteoarthritis surgery? a Swedish twin study

Background: Previous studies have reported an inverse association between educational attainment and different osteoarthritis (OA) outcomes. However, none of the previous studies have accounted for potential confounding by early-life environment and genetics. Thus, we aimed to examine the association between educational attainment and knee and hip OA surgery using twin data. Methods: From the Swed

Hip complaints differ across age and sex : A population-based reference data for the Hip disability and Osteoarthritis Outcome Score (HOOS)

Background: The Hip disability and Osteoarthritis Outcome Score (HOOS) is a self-administered hip-specific questionnaire intended to evaluate symptoms and functional limitations, and it is commonly used to evaluate interventions in individuals with hip dysfunction or hip osteoarthritis. The HOOS consists of 43 questions in five subscales: Pain, Symptoms, Function in daily living, Function in sport

Targeting elevated heme levels to treat a mouse model for Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) is a rare genetic disorder in which patients present a scarcity of erythroid precursors in an otherwise normocellular bone marrow. Most, but not all, patients carry mutations in ribosomal proteins such as RPS19, suggesting that compromised mRNA translation and ribosomal stress are pathogenic mechanisms causing depletion of erythroid precursors. To gain further insight

Advanced dental cleaning is associated with reduced risk of copd exacerbations – a randomized controlled trial

Purpose: Infections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcom

Amyloid β 42 fibril structure based on small-angle scattering

Amyloid fibrils are associated with a number of neurodegenerative diseases, including fibrils of amyloid β42 peptide (Aβ42) in Alzheimer's disease. These fibrils are a source of toxicity to neuronal cells through surface-catalyzed generation of toxic oligomers. Detailed knowledge of the fibril structure may thus facilitate therapeutic development. We use small-angle scattering to provide informati

T cell receptor (TCR) signaling in health and disease

Interaction of the T cell receptor (TCR) with an MHC-antigenic peptide complex results in changes at the molecular and cellular levels in T cells. The outside environmental cues are translated into various signal transduction pathways within the cell, which mediate the activation of various genes with the help of specific transcription factors. These signaling networks propagate with the help of v

Grafts Derived from an α-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson's Disease

BACKGROUND: Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson's disease (PD) and they provide the option of using the patient's own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and fun

Mapping the melanoma plasma proteome (MPP) using single-shot proteomics interfaced with the WiMT database

Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom prote

Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations

The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequenc