Rare Variants in Specific Lysosomal Genes Are Associated With Parkinson's Disease.

Objective: Impaired lysosomal degradation of α-synuclein and other cellular constituents may play an important role in Parkinson's disease (PD). Rare genetic variants in the glucocerebrosidase (GBA) gene were consistently associated with PD. Here we examine the association between rare variants in lysosomal candidate genes and PD.

A systematic review of educational interventions aiming to reduce prehospital delay in patients with acute coronary syndrome.

Interventions aiming at reducing prehospital delay (PHD) in patients with acute coronary syndrome (ACS) have yielded inconsistent findings. Therefore, we aimed to systematically review studies which investigated the impact of educational interventions on reducing PHD in patients with ACS. We searched four electronic databases (Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Embase, Cochrane) from inception throughout December 2016 for studies that reported the impact of either mass-media or personalised intervention on PHD.

Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects.

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants' smoking and sporting habits were measured by a questionnaire.

Protein-coding variants contribute to the risk of atopic dermatitis and skin-specific gene expression.

Background: Fifteen percent of atopic dermatitis (AD) liability-scale heritability could be attributed to 31 susceptibility loci identified by using genome-wide association studies, with only 3 of them (IL13, IL-6 receptor [IL6R], and filaggrin [FLG]) resolved to protein-coding variants.

Objective: We examined whether a significant portion of unexplained AD heritability is further explained by low-frequency and rare variants in the gene-coding sequence.

Methods: We evaluated common, low-frequency, and rare protein-coding variants using exome chip and replication genotype data of 15,574 patients and 377,839 control subjects combined with whole-transcriptome data on lesional, nonlesional, and healthy skin samples of 27 patients and 38 control subjects.

One simple claudication question as first step in Peripheral Arterial Disease (PAD) screening: A meta-analysis of the association with reduced Ankle Brachial Index (ABI) in 27,945 subjects.

Purpose And Methods: A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire.

Early nutrition in combination with polymorphisms in fatty acid desaturase gene cluster modulate fatty acid composition of cheek cells' glycerophospholipids in school-age children.

Variants in the human genes of fatty acid (FA) desaturase 1 (FADS1), 2 (FADS2) and 3 (FADS3) are associated with PUFA blood levels. We explored if maternal prenatal supplementation and children's genetic variation in seventeen SNP of the FADS1, FADS2 and FADS3 gene cluster influence twenty-one of the most relevant cheek cells' derived FA in glycerophospholipids (GPL-FA). The study was conducted in 147 Spanish and German mother-children pairs participating in the Nutraceuticals for a Healthier Life (NUHEAL) study at 8, 9 and 9·5 years.

MTF1 binds to metal-responsive element e within the ATP7B promoter and is a strong candidate in regulating the ATP7B expression.

Wilson's disease is an autosomal recessive disorder resulting from copper excess. Some patients with clinical Wilson's disease symptoms exhibit no or only heterozygous pathogenic variants in the coding region of the disease-causing ATP7B gene. Therefore, the ATP7B promoter region is of special interest.

Usual Dietary Intake Estimation Based on a Combination of Repeated 24-H Food Lists and a Food Frequency Questionnaire in the KORA FF4 Cross-Sectional Study.

Estimation of usual dietary intake poses a challenge in epidemiological studies. We applied a blended approach that combines the strengths provided by repeated 24-h food lists (24HFLs) and a food frequency questionnaire (FFQ). At least two web-based 24HFLs and one FFQ were completed by 821 participants in the KORA FF4 study.

Periodontal Health and Use of Oral Health Services: A Comparison of Germans and Two Migrant Groups.

A cross-sectional study was performed with 251 individuals, consisting of 127 Germans, 68 migrants from Turkey, and 56 resettlers (migrants from the former Soviet Union with German ancestors) to compare periodontal health status, with a special focus on associations with lifestyle and anthropometric factors, and use of dental health services. Maximal pocket depth was used as a clinical surrogate marker for periodontitis. Other variables were obtained by questionnaires administered by a Turkish or Russian interpreter.

A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals.

Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality.

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.

Background: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

Methods: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death.

Psychometric Evaluation of the Major Depression Inventory (MDI) as a Depression Severity Scale in Chinese Patients With Coronary Artery Disease. Findings From the MEDEA FAR-EAST Study.

It is highly recommended that all patients with coronary artery disease should be screened for depression. The Major Depression Inventory (MDI) is a widely used self-rating scale for the assessment of depression but is not valid in Chinese language. The present study was designed to assess the reliability and validity of a version of the MDI translated into Chinese among patients with acute myocardial infarction (AMI).

Longitudinal relationship between B-type natriuretic peptide and anxiety in coronary heart disease patients with depression.

Objective: Patients with coronary heart disease (CHD) suffer from physical limitations, but also from psychological distress. Natriuretic peptides may be involved in the neurobiological processes that modulate psychological adaptation, as they are increased in heart disease and seem to have an anxiolytic-like function. Longitudinal data on this association are scarce.

Performance of the UKPDS Outcomes Model 2 for Predicting Death and Cardiovascular Events in Patients with Type 2 Diabetes Mellitus from a German Population-Based Cohort.

Background And Objective: Accurate prediction of relevant outcomes is important for targeting therapies and to support health economic evaluations of healthcare interventions in patients with diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) risk equations are some of the most frequently used risk equations. This study aims to analyze the calibration and discrimination of the updated UKPDS risk equations as implemented in the UKPDS Outcomes Model 2 (UKPDS-OM2) for predicting cardiovascular (CV) events and death in patients with type 2 diabetes mellitus (T2DM) from population-based German samples.

Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration.

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases.

Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT).

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium.

Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).

Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes).

Hepatic fat is superior to BMI, visceral and pancreatic fat as a potential risk biomarker for neurodegenerative disease.

Objectives: Prior studies relating body mass index (BMI) to brain volumes suggest an overall inverse association. However, BMI might not be an ideal marker, as it disregards different fat compartments, which carry different metabolic risks. Therefore, we analyzed MR-based fat depots and their association with gray matter (GM) volumes of brain structures, which show volumetric changes in neurodegenerative diseases.

Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ultrafine particles and PM in the air of cities around the world: Are they representative of each other?

Can mitigating only particle mass, as the existing air quality measures do, ultimately lead to reduction in ultrafine particles (UFP)? The aim of this study was to provide a broader urban perspective on the relationship between UFP, measured in terms of particle number concentration (PNC) and PM (mass concentration of particles with aerodynamic diameter < 2.5 μm) and factors that influence their concentrations. Hourly average PNC and PM were acquired from 10 cities located in North America, Europe, Asia, and Australia over a 12-month period.

Vertigo and dizziness cause considerable more health care resource use and costs: results from the KORA FF4 study.

Objectives: Vertigo is a common reason for primary care consultations, and its diagnosis and treatment consume considerable medical resources. However, limited information on the specific cost of vertigo is currently available. The aim of this study is to analyse the health care costs of vertigo and examine which individual characteristics would affect these costs.

Seropositivity: Prevalence, Associations, and the Impact on Incident Metabolic Diseases/Risk Factors in the Population-Based KORA Study.

() is a common infection and known risk factor for gastric cancer. We assessed cross-sectional and longitudinal associations to study the impact of seropositivity on metabolic diseases. seropositivity in serum samples of the KORA study was analyzed by multiplex serology.