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Prediction of clinical diagnosis of Alzheimer’s disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years

The strongest genetic risk factor for Alzheimer’s disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) and APOE status to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and

Improving risk assessment in the European Food Safety Authority: lessons from the European Medicines Agency

The recent Regulation (EU) 2019/1381, published on the 6th September 2019, aims to improve the transparency and sustainability of the EU risk assessment in the food chain by amending the General Food Law Regulation (EC 178/2002) and a number of other regulations related to the food sector. This Regulation is introduced as a response to the Fitness Check of the General Food Law Regulation as well a

Quantification and detection of genetic risk factors in the familial aggregation of cancer : Habilitation thesis

SummaryCancer is a multifactorial inheritance disorder caused by a combination of small variations in genes, often acting together with environmental factors. GWASs provide a potential method to investigate the genetic basis of such complex diseases, but they are limited to two main classes of cancer susceptibility variants with different levels of risk and prevalence in the general population: ra

Health Literacy among Swedish Patients in Opioid Substitution Treatment : A Mixed-Methods Study

Background: Poor health and unmet healthcare needs is common among people with substance use disorder (SUD) including patients in opioid substitution treatment (OST). Low health literacy (HL) is associated with poverty, low education and physical limitations, but is unexplored in an OST context. Methods: Mixed-methods were used. Participants were consecutively recruited by clinic staff or research

Temperatures beyond the community optimum promote the dominance of heat-adapted, fast growing and stress resistant bacteria in alpine soils

Alpine soils are warming strongly, leading to profound alterations in carbon cycling and greenhouse gas budgets, mediated via the soil microbiome. To explore microbial responses to global warming, we incubated eight alpine soils between 4 and 35 °C and linked the temperature dependency of bacterial growth with alterations in community structures and the identification of temperature sensitive taxa

Geochronology, whole-rock geochemistry and Sr-Nd isotopes of the Bhanupratappur mafic dyke swarm : Evidence for a common Paleoproterozoic LIP event at 2.37–2.36 Ga in the Bastar and Dharwar cratons

Mafic dykes and dyke swarms in continental settings provide information on the evolution of the subcontinental mantle and can be key elements in the reconstruction of paleo-geographic settings of now separated crustal terranes. This study focuses on the petrogenesis and geochronology of mafic dykes of the WNW (~125°) trending Bhanupratappur swarm in the central Bastar Craton, central India. Dykes

Management of an outbreak of postpartum Streptococcus pyogenes emm75 infections

Background: Streptococcus pyogenes is a well-known cause of postpartum infections and is causing significant morbidity and mortality. Aim: To describe measures taken to control an outbreak of postpartum infections caused by S. pyogenes emm75 on a maternity ward. Methods: Patients presenting postpartum with signs and symptoms of infection were cultured for β-haemolytic streptococci with cervical sw

Energy versus throughput optimisation for machine-to-machine communication

We investigate the trade-off between energy usage and (packet) throughput in wireless mesh networks performing machine-to-machine communication. For this we provide a novel mixed-integer programming formulation to maximise the throughput while maintaining minimal energy usage, together with an effective price-and-branch solution algorithm based on column generation. The resulting optimisation mode

Prespecified 4-Kallikrein Marker Model at Age 50 or 60 for Early Detection of Lethal Prostate Cancer in a Large Population Based Cohort of Asymptomatic Men Followed for 20 Years

PURPOSE: A prespecified statistical model based on 4 kallikrein markers in blood, commercially available as the 4Kscore®, has been shown to accurately detect high grade (greater than Grade Group 2) prostate cancer in men with moderately elevated prostate specific antigen. We assessed whether the model predicted prostate cancer metastasis or death in men not subject to prostate specific antigen scr

Glutenin and gliadin, a piece in the puzzle of their structural properties in the cell described through monte carlo simulations

Gluten protein crosslinking is a predetermined process where specific intra-and intermolecular disulfide bonds differ depending on the protein and cysteine motif. In this article, all-atom Monte Carlo simulations were used to understand the formation of disulfide bonds in gliadins and low molecular weight glutenin subunits (LMW-GS). The two intrinsically disordered proteins appeared to contain mos

Independent Validation of Early-Stage Non-Small Cell Lung Cancer Prognostic Scores Incorporating Epigenetic and Transcriptional Biomarkers With Gene-Gene Interactions and Main Effects

Background: DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. Research Question: Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomi

Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age

Smallpox, one of the most devastating human diseases, killed between 300 million and 500 million people in the 20th century alone. We recovered viral sequences from 13 northern European individuals, including 11 dated to ~600-1050 CE, overlapping the Viking Age, and reconstructed near-complete variola virus genomes for four of them. The samples predate the earliest confirmed smallpox cases by ~100

Oxidation of Polyunsaturated Lipid Membranes by Photocatalytic Titanium Dioxide Nanoparticles : Role of pH and Salinity

In the present study, UV-induced membrane destabilization by TiO2 (anatase) nanoparticles was investigated by neutron reflectometry (NR), small-angle X-ray scattering (SAXS), quartz crystal microbalance with dissipation (QCM-D), dynamic light scattering (DLS), and ζ-potential measurements for phospholipid bilayers formed by zwitterionic palmitoyloleoylphosphatidylcholine (POPC) containing biologic

Blocking Notch-Signaling Increases Neurogenesis in the Striatum after Stroke

Stroke triggers neurogenesis in the striatum in mice, with new neurons deriving in part from the nearby subventricular zone and in part from parenchymal astrocytes. The initiation of neurogenesis by astrocytes within the striatum is triggered by reduced Notch-signaling, and blocking this signaling pathway by deletion of the gene encoding the obligate Notch coactivator Rbpj is sufficient to activat

The association between rheumatoid arthritis and periodontal disease in a population-based cross-sectional case-control study

Background: The association between rheumatoid arthritis (RA) and periodontitis remains unclear. Methods: We studied oral health and periodontitis in a population-based case-control study of individuals with ≥10 remaining teeth ≥61 years of age and either with, or without a diagnosis of RA. 126 dentate individuals with RA were recruited together with age-matched control individuals without RA. The

Proinflammatory cytokines induce accumulation of glypican-1-derived heparan sulfate and the C-terminal fragment of β-cleaved APP in autophagosomes of dividing neuronal cells

Proinflammatory cytokines stimulate expression of β-secretase, which increases processing of amyloid precursor protein (APP), ultimately leading to the deposition of amyloid beta (Aβ). The N-terminal domain of β-cleaved APP supports Cu/NO-dependent release of heparan sulfate (HS) from the glypican-1 (Gpc-1) proteoglycan. HS is an inhibitor of β-secretase, thereby constituting a regulatory, negativ

Registered nurseś views on telephone nursing for patients with respiratory tract infections in primary healthcare - A qualitative interview study

Background: Telephone nursing in primary healthcare has been suggested as a solution to the increased demand for easy access to healthcare, increased number of patients with complex problems, and lack of general practitioners. Registered nurses' assessments may also be of great importance for antibiotic prescriptions according to guidelines. The aim of this study was to describe registered nurses'