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Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes

Type 2 diabetes has been reproducibly clustered into five subtypes with different disease progression and risk of complications; however, etiological differences are unknown. We used genome-wide association and genetic risk score (GRS) analysis to compare the underlying genetic drivers. Individuals from the Swedish ANDIS (All New Diabetics In Scania) study were compared to individuals without diab

Role of FLT3 in Acute Myeloid Leukemia: Molecular mechanisms and Therapeutic opportunities

Acute myeloid leukemia (AML) is a highly heterogeneous blood disease which is characterized by different mutations and chromosomal rearrangements. Nearly 60% of genetic alterations have been found in AML patients involve in signaling pathways including signaling of tyrosine kinase receptor FLT3. FLT3 mutations emerged as one of the most common mutations in AML which represent around 35% of all AML

Low risk patients with acute atrial fibrillation and elevated high-sensitivity troponin do not have increased incidence of pathological stress tests

OBJECTIVES: Many patients with atrial fibrillation (AF) or atrial flutter (AFL) and rapid ventricular response (RVR) have elevated high-sensitivity troponin T (hsTnT) values. Elevated hsTnT is an independent risk marker for cardiovascular events and mortality. The aim was to examine if AF/AFL patients with RVR and elevated hsTnT have an increased incidence of pathological cardiac stress tests, ind

Life satisfaction and adaptation in persons with Parkinson’s disease — A qualitative study

Persons with Parkinson’s disease (PD) need to adapt to their progressive disability to achieve and maintain a high degree of life satisfaction (LS), but little is known about the meaning of LS and adaptation. This study aimed to gain an in-depth understanding of the meaning of LS and adaptation in persons with PD. Open-ended in-depth interviews were performed with 13 persons diagnosed with PD, 9 w

Heparin-binding protein in lower airway samples as a biomarker for pneumonia

Objectives: Ventilator-associated pneumonia (VAP) is difficult to diagnose using clinical criteria and no biomarkers have yet been proved to be sufficiently accurate. The use of the neutrophil-derived Heparin-binding protein (HBP) as a biomarker for pneumonia was investigated in this exploratory case–control study in two intensive care units at a tertiary referral hospital. Methods: Patients with

In vitro differentiation of human pluripotent stem cells into the B lineage using OP9-MS5 co-culture

In vitro differentiation of human pluripotent stem cells (hPSCs) offers a genetically tractable system to examine the physiology and pathology of human tissue development and differentiation. We have used this approach to model the earliest stages of human B lineage development and characterize potential target cells for the in utero initiation of childhood B acute lymphoblastic leukemia. Herein,

3D Engineering of Human Hematopoietic Niches in Perfusion Bioreactor

The hematopoietic microenvironment, also referred to as hematopoietic niche, is a functional three-dimensional (3D) unit of the bone marrow (BM) that planar culture systems cannot recapitulate. Existing limitations of 2D protocols are driving the development of advanced 3D methodologies, capable of superior modeling of the native organization and interactions between hematopoietic cells and their

Dopamine Neuron Diversity : Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing

Human midbrain dopamine (DA) neurons are a heterogeneous group of cells that share a common neurotransmitter phenotype and are in close anatomical proximity but display different functions, sensitivity to degeneration, and axonal innervation targets. The A9 DA neuron subtype controls motor function and is primarily degenerated in Parkinson's disease (PD), whereas A10 neurons are largely unaffected

Stem Derived Dopamine Neurons : Will They Replace DBS as the Leading Neurosurgical Treatment for Parkinson's Disease?

The use of stem cell derived dopamine neurons for treating patients with Parkinson's disease has now evolved to the first in human clinical trials. In this debate, we argue that assuming these trials give positive outcomes that this therapy will supercede DBS as the neurosurgical treatment of choice for PD patients in the future given it is a one-off therapy that repairs a critical pathway in the

GDNF Therapy : Can We Make It Work?

In two recent postmortem studies, Jeffrey Kordower and colleagues report new findings that open up for an interesting discussion on the status of GDNF/NRTN signaling in patients with Parkinson's disease (PD), adding an interesting perspective on the, admittedly very limited, signs of restorative effects previously seen in GDNF/NRTN-treated patients. Their new findings show that the level of the GD

Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes

AIMS: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes (T2D). The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior inter

The role of citrulline, intestinal fatty acid–binding protein, and D-dimer as potential biomarkers in the diagnosis of internal herniation after Roux-en-Y gastric bypass

Background: Diagnosing internal herniation (IH) in Roux-en-Y gastric bypass (RYGB) patients with acute abdominal pain poses a diagnostic challenge. Diagnostic laparoscopy is often required for a definitive diagnosis. We hypothesized that intestinal ischemia biomarkers would aid in the diagnosing of IH. Objectives: To explore intestinal ischemia biomarkers in diagnosing IH. Setting: University Hosp

RUBIC (ReproUnion Biobank and Infertility Cohort) : A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity

Background: Infertility affects 15%–25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples

Right ventricular stroke work index by echocardiography in adult patients with pulmonary arterial hypertension

BACKGROUND: In adult patients with pulmonary arterial hypertension (PAH), right ventricular (RV) failure may worsen rapidly, resulting in a poor prognosis. In this population, non-invasive assessment of RV function is challenging. RV stroke work index (RVSWI) measured by right heart catheterization (RHC) represents a promising index for RV function. The aim of the present study was to comprehensiv

Fibroblast growth factor 23 is an independent marker of COPD and is associated with impairment of pulmonary function and diffusing capacity

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in recent years has been reported to have significant effects on numerous tissues. Chronic obstructive pulmonary disease (COPD) is associated with hypophosphatemia but the evidence for elevated plasma levels of FGF23 in COPD subjects is ambiguous. Recently, FGF23 has even been shown to be involved in the inflammatory pathways activ

The copy number variation and stroke (CaNVAS) risk and outcome study

Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and e

Photoelectrochemical oxidation in ambient conditions using earth-abundant hematite anode : A green route for the synthesis of biobased polymer building blocks

This study demonstrates the use of a photoelectrochemical device comprising earth-abundant hematite photoanode for the oxidation of 5-hydroxymethylfurfural (5-HMF), a versatile bio-based platform chemical, under ambient conditions in the presence of an electron mediator. The results obtained in this study showed that the hematite photoanode, upon doping with fluorine, can oxidize water even at low

Polyphenol intake and epithelial ovarian cancer risk in the european prospective investigation into cancer and nutrition (Epic) study

Despite some epidemiological evidence on the protective effects of polyphenol intake on epithelial ovarian cancer (EOC) risk from case-control studies, the evidence is scarce from prospective studies and non-existent for several polyphenol classes. Therefore, we aimed to investigate the associations between the intake of total, classes and subclasses of polyphenols and EOC risk in a large prospect

The role of full-length apoE in clearance of Gram-negative bacteria and their endotoxins

ApoE is a well-known lipid-binding protein that plays a main role in the metabolism and transport of lipids. More recently, apoE-derived peptides have been shown to exert antimicrobial effects. Here, we investigated the antibacterial activity of apoE using in vitro assays, advanced imaging techniques, and in vivo mouse models. The formation of macromolecular complexes of apoE and endotoxins from G