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Perfusion in Upper Eyelid Flaps : Effects of Rotation and Stretching Measured With Laser Speckle Contrast Imaging in Patients

PURPOSE: The aim of this study was to investigate how the blood perfusion in human upper eyelid skin flaps is affected by the length of the flap and the degree of stretching and rotation of the flap.METHODS: Twenty-nine upper eyelids were dissected as part of a blepharoplastic procedure in patients. The 1-cm wide proximal end of the flap remains attached, to mimic a random pattern skin flap (herea

Aerosolization and recovery of viable murine norovirus in an experimental setup

Noroviruses are the major cause for viral acute gastroenteritis in the world. Despite the existing infection prevention strategies in hospitals, the disease continues to spread and causes extensive and numerous outbreaks. Hence, there is a need to investigate the possibility of airborne transmission of norovirus. In this study, we developed an experimental setup for studies on the infectivity of a

Isolation of high yield and quality RNA from human precision-cut lung slices for RNA-sequencing and computational integration with larger patient cohorts

Precision-cut lung slices (PCLS) have gained increasing interest as a model to study lung biology/disease and screening novel therapeutics. In particular, PCLS derived from human tissue can better recapitulate some aspects of lung biology/disease as compared to animal models. Several experimental readouts have been established for use with PCLS, but obtaining high yield and quality RNA for downstr

Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip

Objective Atrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity and mortality. Its increasing prevalence calls for novel biomarkers to identify underlying pathophysiological mechanisms as well as patients at risk. Methods Plasma samples from 1694 individuals from the Swedish population-based Malmö Preventive Project (mean age 69.5 years; 29.3% female; mean

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and e

Loss of Cxcr5 alters neuroblast proliferation and migration in the aged brain

Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neuroge

S100A6 is a critical regulator of hematopoietic stem cells.

The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell

Prospects for improved glomerular filtration rate estimation based on creatinine—results from a transnational multicentre study

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved.MethodsIn a cro

Impact of α-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized α-synuclein rat model of PD

Preclinical assessment of the therapeutic potential of dopamine (DA) neuron replacement in Parkinson's disease (PD) has primarily been performed in the 6-hydroxydopamine toxin model. While this is a good model to assess graft function, it does not reflect the pathological features or progressive nature of the disease. In this study, we establish a humanized transplantation model of PD that better

Organ-Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy

Nanoparticle-based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C chemokine receptor type 2 is explored in lung tumors

Enhancing mitochondrial function in vivo rescues MDS-like anemia induced by pRb deficiency

Erythropoiesis is intimately coupled to cell division, and deletion of the cell cycle regulator retinoblastoma protein (pRb) causes anemia in mice. Erythroid-specific deletion of pRb has been found to result in inefficient erythropoiesis because of deregulated coordination of cell cycle exit and mitochondrial biogenesis. However, the pathophysiology remains to be fully described, and further chara

Cognitive test results are associated with mortality and rehospitalization in heart failure : Swedish prospective cohort study

AIMS: We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort.METHODS AND RESULTS: Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making T

Costing analysis of a digital first-line treatment platform for patients with knee and hip osteoarthritis in Sweden

Osteoarthritis (OA) constitutes a major and increasing burden on patients, health care systems and the broader society. It is estimated that around a quarter of the adult population is affected by OA in the knee and hip and that the prevalence of OA will increase over the coming decades largely due to aging and adverse life-style factors. Prevention and effective care are critical to manage the ch

Antisense regulation of atrial natriuretic peptide expression

The cardiac hormone atrial natriuretic peptide (ANP) is a central regulator of blood volume and a therapeutic target in hypertension and heart failure. Enhanced ANP activity in such conditions through inhibition of the degradative enzyme neprilysin has shown clinical efficacy but is complicated by consequences of simultaneous accumulation of a heterogeneous array of other hormones. Targets for spe

Evaluation of TH-Cre knock-in cell lines for detection and specific targeting of stem cell-derived dopaminergic neurons

The focal and progressive degeneration of dopaminergic (DA) neurons in ventral midbrain has made Parkinson's disease (PD) a particularly interesting target of cell-based therapies. However, ethical issues and limited tissue availability have so far hindered the widespread use of human fetal tissue in cell-replacement therapy. DA neurons derived from human pluripotent stem cells (hPSCs) offer unpre

Antibodies against phosphorylcholine in hospitalized versus non‑hospitalized obese subjects

Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties. Here, we explored the role of anti-PC in hospitalized versus non-hospi

Proteomic and Metabolomic Characterization of Metabolically Healthy Obesity: : A Descriptive Study from a Swedish Cohort

Background/Aims. Obesity is a well-established risk factor for the development of numerous chronic diseases. However, there is a small proportion of obese individuals that seem to escape these aforementioned conditions—Metabolically Healthy Obesity (MHO). Our aim was to do a metabolic and biomarker profiling of MHO individuals. Method. Associations between different biomarkers (proteomics, lipidom

Dietary Data in the Malmö Offspring Study : Reproducibility, Method Comparison and Validation against Objective Biomarkers

Irregular dietary intakes impairs estimations from food records. Biomarkers and method combinations can be used to improve estimates. Our aim was to examine reproducibility from two assessment methods, compare them, and validate intakes against objective biomarkers. We used the Malmö Offspring Study (55% women, 18-71 y) with data from a 4-day food record (4DFR) and a short food frequency questionn

Human Atherosclerotic Plaque Progression Is Dependent on Apoptosis According to Bomb-Pulse 14C Dating

Individuals with rapidly progressing atherosclerotic plaques are at higher risk of experiencing acute complications. Currently, we lack knowledge regarding factors in human plaque that cause rapid progression. Using the 14C bomb-pulse dating method, we assessed the physical age of atherosclerotic plaques and which biological processes were associated with rapidly progressing plaques. Interestingly

Temporal trends in characteristics and outcome of heart failure patients with and without significant coronary artery disease

Aims: Ischaemic coronary artery disease (CAD) remains the leading cause of mortality globally due to sudden death and heart failure (HF). Invasive coronary angiography (CAG) is the gold standard for evaluating the presence and severity of CAD. Our objective was to assess temporal trends in CAG utilization, patient characteristics, and prognosis in HF patients undergoing CAG at a national level. Me