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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

Protein Expression in Metastatic Melanoma and the Link to Disease Presentation in a Range of Tumor Phenotypes

Malignant melanoma is among the most aggressive skin cancers and it has among the highest metastatic potentials. Although surgery to remove the primary tumor is the gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased survival. To improve survival rates and life span, advanced treatme

Glucose-Dependent Insulinotropic Peptide in the High-Normal Range Is Associated With Increased Carotid Intima-Media Thickness

OBJECTIVE: While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide 1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortalit

Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults

Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids. Methods: Participants from the GLACIER Study (Nmax = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms

A novel two-factor monosynaptic TRIO tracing method for assessment of circuit integration of hESC-derived dopamine transplants

Transplantation in Parkinson's disease using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons is a promising future treatment option. However, many of the mechanisms that govern their differentiation, maturation, and integration into the host circuitry remain elusive. Here, we engrafted hESCs differentiated toward a ventral midbrain DA phenotype into the midbrain of a preclinical

Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals

Background: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods: Participa

Single-step generation of 1D FeCo nanostructures

Magnetic one-dimensional structures are attractive nanomaterials due to the variety of potential applications they can provide. The fabrication of bimetallic 1D structures further expands the capabilities of such structures by tailoring the magnetic properties. Here, a single-step template-free method is presented for the fabrication of 1D FeCo alloy nanochains. In this approach, charged single-cr

Scanning WAXS microscopy of regenerated cellulose fibers at mesoscopic resolution

In this work, regenerated cellulose textile fibers, Ioncell-F, dry-wet spun with different draw ratios, have been investigated by scanning wide-Angle X-ray scattering (WAXS) using a mesoscopic X-ray beam. The fibers were found to be homogeneous on the 500nm length scale. Analysis of the azimuthal angular dependence of a crystalline Bragg spot intensity revealed a radial dependence of the degree of

Exploring the Functional Landscape of the p53 Regulatory Domain : The Stabilizing Role of Post-Translational Modifications

This study focuses on the intrinsically disordered regulatory domain of p53 and the impact of post-translational modifications. Through fully atomistic explicit water molecular dynamics simulations, we show the wealth of information and detailed understanding that can be obtained by varying the number of phosphorylated amino acids and implementing a restriction in the conformational entropy of the

Visual acuity in patients with non-functioning pituitary adenoma : Prognostic factors and long-term outcome after surgery

Background: Visual acuity (VA) and visual field defects (VF) are evaluated in the preoperative management of non-functioning pituitary adenoma (NFPA). The former is less studied than the latter. Research question: To analyze preoperative factors, including adenoma volumetry, associated with reduced VA and postoperative improvement of VA over five years after surgery. Methods: Eighty-seven patients

Add-on pramipexole for anhedonic depression : study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden

INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is nee

Effect of Different In2O3(111) Surface Terminations on CO2 Adsorption

In2O3-based catalysts have shown high activity and selectivity for CO2 hydrogenation to methanol; however, the origin of the high performance of In2O3 is still unclear. To elucidate the initial steps of CO2 hydrogenation over In2O3, we have combined X-ray photoelectron spectroscopy and density functional theory calculations to study the adsorption of CO2 on the In2O3(111) crystalline surface with

Structure and morphology of vesicular dispersions based on novel phosphatidyl glucose and phosphatidyl choline with different acyl chains

Hypothesis: Phospholipids are widely used in food and pharmacological formulations. However, these typically suffer from limitations such as low colloidal stability. Promising stability has been observed for vesicles based on phosphatidylglucose (P-Glu), but fundamental knowledge on this lipid is missing and those observations were made using P-Glu containing mixed acyl groups. The acyl groups are

Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort

Previous research indicates that insulin-like growth factor binding protein 7 (IGFBP7) protein levels in breast cancer tissue and blood are prognostic. However, genetic determinants of IGFBP7 in breast cancer remain largely unexplored. We examined IGFBP7 in a cohort of 1701 patients with a first breast cancer from Sweden, enrolled prior to surgery 2002-2016 and followed for up to 15 years. Genotyp

Thrombotic risk determined by ABO, F8, and VWF variants in a population-based cohort study

Background Von Willebrand factor (VWF) and coagulation factor VIII (FVIII) plasma levels are associated with increased risk for venous thromboembolism (VTE). Objectives This study aimed to determine the thrombotic risk of rare and common variants of 27 genes linked to VWF or FVIII plasma levels in genome-wide association studies. Methods Exon sequences of 27 genes linked to plasma levels of VWF or