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Cerebro-spinal fluid biomarker levels : phosphorylated tau (T) and total tau (N) as markers for rate of progression in Alzheimer's disease

BACKGROUND: We investigated the potential associations between cerebro-spinal fluid (CSF) levels of phosphorylated tau (P-tau) and total tau (T-tau) with short-term response to cholinesterase inhibitor (ChEI) treatment, longitudinal outcome and progression rates in Alzheimer's disease (AD). METHODS: This prospective, observational study included 129 participants clinically diagnosed with mild-to-m

Second primary cancers in melanoma patients critically shorten survival

Background: Survival in malignant cutaneous melanoma has improved but increasing survival will result in an increased likelihood of the occurrence of second primary cancers (SPCs). SPCs may adversely interfere with survival. We quantified survival in patients with different types of SPCs, in comparison to known poor prognostic indicators of metastatic disease. Methods: Data for melanoma and any SP

Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis

The Mixed Lineage Leukemia (MLL1, KMT2A) gene is critical for development and maintenance of hematopoietic stem cells (HSCs), however, whether this protein is limiting for HSC development is unknown due to lack of physiologic model systems. Here, we develop an MLL1-inducible embryonic stem cell (ESC) system and show that induction of wild-type MLL1 during ESC differentiation selectively increases

The catalytic nature of protein aggregation

The formation of amyloid fibrils from soluble peptide is a hallmark of many neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Characterization of the microscopic reaction processes that underlie these phenomena have yielded insights into the progression of such diseases and may inform rational approaches for the design of drugs to halt them. Experimental evidence suggests th

Epilepsy in immigrants and Swedish-born : A cohort study of all adults 18 years of age and older in Sweden

Purpose: We aimed to study the association between country of birth and incident epilepsy in several immigrant groups using Swedish-born individuals as referents. Method: The study population included all adults aged 18 years and older in Sweden, living and deceased, 6,690,598 in the first-generation and 6,683,125 in the second-generation sub-study. Epilepsy was defined as having at least one regi

Maternal half-sibling families with discordant fathers : A contrastive design assessing cross-generational paternal genetic transmission of alcohol use disorder, drug abuse and major depression

BackgroundWe introduce and apply an elegant, contrastive genetic-epidemiological design - Maternal Half-Sibling Families with Discordant Fathers - to clarify cross-generational transmission of genetic risk to alcohol use disorder (AUD), drug abuse (DA) and major depression (MD).MethodUsing Swedish national registries, we identified 73 108 eligible pairs of reared together maternal half-siblings an

J-curve association between alcohol intake and varicose veins in Japan : The Shimane CoHRE Study

The effect of alcohol intake on varicose veins (VV) has not been determined by its consumption level. The aim of this study was to investigate the association between alcohol intake and VV in an elderly general population. Using a cross-sectional approach, the Shimane CoHRE Study data, comprising a total of 1060 participants, were analyzed. By multivariate regression analysis adjusted with basic c

Modeling the assembly of oppositely charged lock- and key-colloids

The interaction of oppositely charged lock- and key-colloids is investigated using computer simulations. We show that indented spheres, i.e., lock-particles, can be specifically assembled with spherical key-particles using solely electrostatic interactions in addition to a hard overlap potential. An analytic description of the entropic and energetic contributions is derived and supported by simula

Antihypertensive drugs and relevant cardiovascular pharmacotherapies and the risk of incident dementia in patients with atrial fibrillation

Background: Atrial fibrillation (AF) and dementia are predominant among the elderly; patients with AF have an increased dementia risk. We aimed to study if prescribed antihypertensive drugs and cardiovascular pharmacotherapies are associated with a lower relative risk of dementia. Methods: All included patients were ≥45 years and diagnosed with AF in primary care; 12,096 (6580 men and 5516 women)

Socioeconomic factors and mortality in patients with atrial fibrillation-a cohort study in Swedish primary care

Background: Preventing ischaemic stroke attracts significant focus in atrial fibrillation (AF) cases. Less is known on the association between socioeconomic factors and mortality and cardiovascular outcomes in patients with AF. Methods: Our study population included adults (n=12 283) ≥45 years diagnosed with AF at 75 primary care centres in Sweden 2001-07. Cox regression was used to calculate haza

Associations between relevant cardiovascular pharmacotherapies and incident heart failure in patients with atrial fibrillation : A cohort study in primary care

Objective: To study association between relevant cardiovascular pharmacotherapy and incident congestive heart failure (CHF) in patients with atrial fibrillation treated in primary health care. Methods: Study population included all adults (n=7975) aged 45 years and older diagnosed with atrial fibrillation at 75 primary care centers in Sweden between 2001 and 2007. Outcome was defined as a first di

Pre-diabetes and diabetes are independently associated with adverse cognitive test results : A cross-sectional, population-based study

Background: Diabetes is a risk factor for cognitive impairment, but whether there is also a link between pre-diabetes and cognitive dysfunction is not yet fully established. The aim of this observational study was to investigate associations between pre-diabetes/diabetes and cognitive test results, and also between glucose levels measured during the Oral Glucose Tolerance Test (OGTT) and cognitive

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

Immunophenotypic characterization and molecular analysis have long been used to delineate heterogeneity and define distinct cell populations. FACS is inherently a single-cell assay, however prior to molecular analysis, the target cells are often prospectively isolated in bulk, thereby losing single-cell resolution. Single-cell gene expression analysis provides a means to understand molecular diffe

Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis

Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loc

Heart failure in immigrant groups : a cohort study of adults aged 45 years and over in Sweden

Objective. An increased risk of being diagnosed with coronary heart disease or atrial fibrillation has been shown among different immigrant groups. However, less is known on the risk of being diagnosed with congestive heart failure (CHF). Design. We studied CHF in immigrants including all adults ≥45 years in Sweden (n = 3,274,119) from 1998 to 2012. CHF was defined as at the first event registered

The impact of parenthood on risk of registration for alcohol use disorder in married individuals : A Swedish population-based analysis

BackgroundAlthough being married with children is associated with a reduced rate of alcohol use disorder (AUD), is this finding independent of a marital effect, different in mothers and fathers and potentially causal in effect.MethodsUsing Cox proportional hazards, we examined, in 1 252 237 married individuals, the association between a resident younger and older child and risk for AUD registratio