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TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity.

The aggregation of α-synuclein plays a major role in Parkinson disease (PD) pathogenesis. Recent evidence suggests that defects in the autophagy-mediated clearance of α-synuclein contribute to the progressive loss of nigral dopamine neurons. Using an in vivo model of α-synuclein toxicity, we show that the PD-like neurodegenerative changes induced by excess cellular levels of α-synuclein in nigral

The effects of a cancer diagnosis on the health of a patient's partner : a population-based registry study of cancer in Sweden

The aim of this population-based registry study was to explore how cancer influences the health of partners, by examining the onset of new diagnoses for partners, health care use and health care costs among partners living with patients with cancer. The sample consisted of partners of patients with cancer (N = 10 353) and partners of age- and sex-matched controls who did not have cancer (N = 74 59

The BRCA1-Δ11q alternative splice isoform bypasses germline mutations and promotes therapeutic resistance to PARP inhibition and cisplatin

Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a B

Blood Metabolic Signatures of Body Mass Index : A Targeted Metabolomics Study in the EPIC Cohort

Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from t

Brain damage and behavioural disorders in fish induced by plastic nanoparticles delivered through the food chain

The tremendous increases in production of plastic materials has led to an accumulation of plastic pollution worldwide. Many studies have addressed the physical effects of large-sized plastics on organisms, whereas few have focused on plastic nanoparticles, despite their distinct chemical, physical and mechanical properties. Hence our understanding of their effects on ecosystem function, behaviour

SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111

Risk of low bone mineral density in testicular germ cell cancer survivors : Association with hypogonadism and treatment modality

The cure rate of testicular cancer exceeds 95%, but testicular cancer survivors (TCS) are at increased risk of hypogonadism (HG). It has been suggested that TCS have reduced bone mineral density (BMD), but it is unclear whether this is related to HG or a direct effect of cancer therapy. The aim of this study was to evaluate whether TCS have decreased BMD, and if BMD is related to HG and/or the can

Utilization of genetic data can improve the prediction of type 2 diabetes incidence in a Swedish cohort

The aim of this study was to measure the impact of genetic data in improving the prediction of type 2 diabetes (T2D) in the Malmö Diet and Cancer Study cohort. The current study was performed in 3,426 Swedish individuals and utilizes of a set of genetic and environmental risk data. We first validated our environmental risk model by comparing it to both the Finnish Diabetes Risk Score and the T2D r

High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer

Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC

Orthostatic Hypotension Predicts Incidence of Heart Failure: The Malmö Preventive Project.

BackgroundThe presence of orthostatic hypotension (OH) predicts all-cause mortality and incident cardiovascular disease. Whether or not OH is associated with the development of heart failure (HF) remains unknown.MethodsIn this Swedish population-based prospective study (the Malmö Preventive Project), the incidence of HF in relation to baseline OH, defined as decrease in systolic (SBP) >/=20 mm Hg

Associations of alcohol use disorders with esophageal and gastric cancers: a population-based study in Sweden.

Alcohol consumption is associated with squamous cell carcinoma of the esophagus, but little is known about whether alcohol consumption is associated with adenocarcinoma of the esophagus and gastric cancer, which we attempt to clarify in this study. Individuals with alcohol use disorders were identified from the nation-wide Swedish Hospital Discharge Register and Outpatient Register, the Crime Regi

Atrial fibrillation in the Malmö diet and cancer study: a study of occurrence, risk factors and diagnostic validity.

The validity of atrial fibrillation (AF) diagnoses in national registers for use as endpoints in prospective studies has not been evaluated. We studied the validity of AF diagnoses in Swedish national hospital discharge and cause of death registers and the occurrence of and risk factors for AF in a middle-aged Swedish population using these registers. Our study included the 30,447 individuals (age

Androgen receptor htSNPs in relation to androgen levels and OC use in young women from high-risk breast cancer families.

High testosterone levels have been associated with breast cancer. BRCA1 may function as an androgen receptor (AR) co-regulator. We aimed to examine AR haplotype-tagging single-nucleotide polymorphisms (AR htSNPs) and diplotypes in relation to in vivo androgen levels, combined OC use, CAG and GGC genotypes, and BRCA1/2/X family status in 269 young healthy women from breast cancer high-risk families

Evaluation of Human Papillomavirus Antibodies and Risk of Subsequent Head and Neck Cancer.

PURPOSEHuman papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera. METHODSWe identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oro

Glomerular filtration rate in patients with atrial fibrillation on warfarin treatment: A subgroup analysis from the AURICULA registry in Sweden.

INTRODUCTION: Numerous associations between chronic kidney disease (CKD) and atrial fibrillation (AF) have been reported and patients with CKD on anticoagulation therapy have an increased risk of bleeding. Currently, new anticoagulant agents are emerging in clinical practice, some of which are excreted by the kidneys. The proportion of AF patients on anticoagulant treatment with reduced renal func

Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.

Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were

Anthropometric factors and ovarian cancer risk in the Malmö Diet and Cancer Study.

Objective: To examine the associations of measured anthropometric factors, including general and central adiposity, with epithelial ovarian cancer (EOC) risk in the Malmö Diet and Cancer Study. Methods: In 93 incident EOC cases from a Swedish population-based prospective cohort study, seven anthropometric factors; height, weight, BMI, body fat percentage, waist- and hip circumference, and waist-hi

Incidence of Coronary Events and Case Fatality Rate in Relation to Blood Lymphocyte and Neutrophil Counts.

OBJECTIVE: Elevated levels of blood leukocytes have been associated with acute coronary events (CEs), but data on leukocyte subclasses are limited. This study aimed to explore whether blood lymphocyte and neutrophil counts are associated with incidence of CEs and with fatal outcome in subjects who subsequently experienced a first CE. METHODS AND RESULTS: Neutrophil and lymphocyte counts were measu