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Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson's disease therapy

Parkinson's disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathway

Genetic Risk Prediction of Atrial Fibrillation

BACKGROUND—: Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. METHODS—: To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of Europea

The influence of native language word order and cognitive biases in pictorial event representations

Ever since Goldin-Meadow, S., C. Mylander, W. C. So, and A. Özyürek. 2008. The natural order of events: How speakers of different languages represent events nonverbally. PNAS 105: 9163–9168. proposed that there is a preferred order in sequential non-verbal event representations (Actor > Patient > Act), apparently independent of the default word order in one’s native language, the topic has been th

Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

Background Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. Objectives This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysi

The Physical Housing Environment and Subjective Well-Being Among Older People Using Long-Term Care Services in Japan

For older people using long-term care services, the conditions of their life-space may be critical. The relationships between the physical housing environment and aspects of health were examined among older people in Japan (aged 65+ years, N = 1,928) by multivariable logistic regression analysis, adjusting for sociodemographic characteristics. Lack of safety, low access to emergency assistance, lo

Unique animal friendly 3D culturing of human cancer and normal cells

Two-dimensional cell culturing has proven inadequate as a reliable preclinical tumour model due to many inherent limitations. Hence, novel three-dimensional (3D) cell culture models are needed, which in many aspects can mimic a native tumour with 3D extracellular matrix. Here, we present a 3D electrospun polycaprolactone (PCL) mesh mimicking the collagen network of tissue. The naturally hydrophobi

Depletion of the transcriptional coactivators CREB-binding protein or EP300 downregulates CD20 in diffuse large B-cell lymphoma cells and impairs the cytotoxic effects of anti-CD20 antibodies

Monoclonal antibodies targeting CD20 are central in the treatment of B-cell lymphomas. In diffuse large B-cell lymphoma (DLBCL), inactivating mutations of the histone acetyltransferases CREB-binding protein (CBP) and EP300 are common. Moreover, knockdown of CBP in DLBCL has been shown to result in aberrant transcriptional silencing. Expression of CD20 is sensitive to epigenetic manipulation, and h

Homelessness and risk of end-stage renal disease

To identify homeless people with chronic kidney disease (CKD) who were at highest risk for end-stage renal disease (ESRD), we studied 982 homeless and 15,674 domiciled people with CKD receiving public health care. We developed four risk prediction models for the primary outcome of ESRD. Overall, 71 homeless and 888 domiciled people progressed to ESRD during follow-up (median: 6.6 years). Homeless

COSCA (Core Outcome Set for Cardiac Arrest) in Adults : An Advisory Statement From the International Liaison Committee on Resuscitation

Cardiac arrest effectiveness trials have traditionally reported outcomes that focus on survival. A lack of consistency in outcome reporting between trials limits the opportunities to pool results for meta-analysis. The COSCA initiative (Core Outcome Set for Cardiac Arrest), a partnership between patients, their partners, clinicians, research scientists, and the International Liaison Committee on R

COSCA (Core Outcome Set for Cardiac Arrest) in Adults : An Advisory Statement From the International Liaison Committee on Resuscitation

Cardiac arrest effectiveness trials have traditionally reported outcomes that focus on survival. A lack of consistency in outcome reporting between trials limits the opportunities to pool results for meta-analysis. The COSCA initiative (Core Outcome Set for Cardiac Arrest), a partnership between patients, their partners, clinicians, research scientists, and the International Liaison Committee on R

Functional Screening Identifies MicroRNA Regulators of Corin Activity and Atrial Natriuretic Peptide Biogenesis

Atrial natriuretic peptide (ANP) represents an attractive therapeutic target in hypertension and heart failure. The biologically active form of ANP is produced by the cardiac serine protease corin, and modulation of its activity might therefore represent a novel approach for ANP augmentation. MicroRNAs (miRNAs) are pervasive regulators of gene expression, but their potential role in regulating cor

Novel functional proteins coded by the human genome discovered in metastases of melanoma patients

In the advanced stages, malignant melanoma (MM) has a very poor prognosis. Due to tremendous efforts in cancer research over the last 10 years, and the introduction of novel therapies such as targeted therapies and immunomodulators, the rather dark horizon of the median survival has dramatically changed from under 1 year to several years. With the advent of proteomics, deep-mining studies can reac

Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants

Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporter

Plasma Lipidome and Prediction of Type 2 Diabetes in the Population-Based Malmö Diet and Cancer Cohort

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with dyslipidemia, but the detailed alterations in lipid species preceding the disease are largely unknown. We aimed to identify plasma lipids associated with development of T2DM and investigate their associations with lifestyle. RESEARCH DESIGN AND METHODS: At baseline, 178 lipids were measured by mass spectrometry in 3,668 participants wit

Low bone mineral density is associated with hypogonadism and cranial irradiation in male childhood cancer survivors

Summary: We investigated if bone mineral density was related to testosterone deficiency and/or previous cancer treatment in men who were childhood cancer survivors. Men with untreated testosterone deficiency or previous treatment with cranial irradiation were at increased risk of impaired bone health. Prevention of osteoporosis should be considered in their follow-up. Introduction: Childhood cance