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A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study

Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportio

Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

Background/purpose: The objective of this study was to explore the impact of systemic lupuserythematosus and belimumab given in addition to standard of care therapy on 13-valentconjugated pneumococcal vaccine (PCV13) response. Methods: Forty-seven systemic lupuserythematosus patients and 21 healthy controls were immunized with a single dose of13-valent conjugated pneumococcal vaccine. Forty system

Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study : A cohort study of 21,297 childhood cancer survivors

Background: Survivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer. Metho

Amino Acid Signatures to Evaluate the Beneficial Effects of Weight Loss

Aims. We investigated the relationship between circulating amino acid levels and obesity; to what extent weight loss followed by weight maintenance can correct amino acid abnormalities; and whether amino acids are related to weight loss. Methods. Amino acids associated with waist circumference (WC) and BMI were studied in 804 participants from the Malmö Diet and Cancer Cardiovascular Cohort (MDC-C

Lentiviral Vectors with Cellular Promoters Correct Anemia and Lethal Bone Marrow Failure in a Mouse Model for Diamond-Blackfan Anemia

Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with Diamond-Blackfan anemia have mutations in a gene encoding ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral vector with the spleen focus-forming virus promoter, we demonstrated that the Diamon

Familial Aggregation of Aortic Valvular Stenosis : A Nationwide Study of Sibling Risk

Background - Aortic valvular stenosis (AS) is the most common cause of cardiac valvular replacement surgery. During the last century, the pathogenesis of AS has undergone transitions in developed countries, from rheumatic heart disease to a degenerative calcific pathogenesis. Although a familial component has been described for a subset of cases with a bicuspid valve, data are limited on the overa

Predominance of girls with cancer in families with multiple childhood cancer cases

Background: Recent studies indicate that one of four childhood cancers can be attributed to hereditary genetic abnormalities. Methods: The Lund Childhood Cancer Genetic study includes newly diagnosed childhood cancer patients as well as childhood cancer survivors visiting the Department of Pediatrics or the Late Effect Clinic at Skåne University Hospital, Lund, Sweden. Questionnaires regarding fam

Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

To understand the developmental trajectories in early lymphocyte differentiation, we identified differentially expressed surface markers on lineage-negative lymphoid progenitors (LPs). Single-cell polymerase chain reaction experiments allowed us to link surface marker expression to that of lineage-associated transcription factors (TFs) and identify GFRA2 and BST1 as markers of early B cells. Funct

Familial Risks of Heart Failure in Sweden

Hjärtsvikt betecknar ett syndrom som innebär att hjärtat har otillräcklig förmåga att försörja kroppen med blod. Detta kan antingen bero på att hjärtat inte kan fyllas med eller stöta ut tillräckligt med mängd blod. Patienter med hjärtsvikt har i allmänhet hög dödlighet, detta trots att stora framsteg har gjorts avseende behandlingen av hjärtsvikt, speciellt sedan 1980-talet. Femårsöverlevnaden föIntroduction: Despite major advances, the incidence rate and mortality of heart failure (HF) remains high, with a five-year survival of approximately 50%. At the time of inception of this thesis the familial risks of HF, including the aspects of mortality, were largely underdetermined. This thesis is composed of four papers with the main aims as follows:To determine the risk of hospitalization of

Systematic Analysis of MicroRNAs Targeting the Androgen Receptor in Prostate Cancer Cells.

Androgen receptor (AR) is expressed in all stages of prostate cancer progression, including in castration-resistant tumors. Eliminating AR function continues to represent a focus of therapeutic investigation, but AR regulatory mechanisms remain poorly understood. To systematically characterize mechanisms involving microRNAs (miRNAs), we conducted a gain-of function screen of 1129 miRNA molecules i

Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.

The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody

Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke.

OBJECTIVE: Serum and glucocorticoid regulated kinase 1 (SGK1) expression is increased by aldosterone and is a key regulator of the amiloride-sensitive sodium channel (ENaC) in the distal nephron. We have previously shown that two SNPs in SGK1 (rs1057293 and rs1743966) are associated with blood pressure variation and blood pressure progression in the general population. Therefore, we tested the ass

HLA-DQB1 genotypes and islet cell autoantibodies against GAD65 and IA-2 in relation to development of diabetes post partum in women with gestational diabetes mellitus.

AIMS: To study HLA-DQB1 genes and islet cell autoantibodies against glutamic acid decarboxylase 65 (GADA) and insulinoma antigen-2 (IA-2A) in relation to diabetes post partum in mothers with diagnosed gestational diabetes mellitus (GDM). METHODS: During 2003-2004, women undergoing a 75g oral glucose tolerance test (OGTT) during pregnancy were invited to participate in the Mamma Study. Cut-off leve

Tumour-suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model

Oestrogen receptor β (ERβ) has been suggested to have anti-proliferative and anti-tumour effects in breast and prostate cancer cells, but other studies have indicated its tumour-promoting effects. Understanding the complex effects of this receptor in different contexts requires further study. We reported that high ERβ expression is independently associated with improved prognosis in female colorec

Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons

Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons for brain repair. Proof of concept for direct neuronal reprogramming of glial progenitors has been obtained in mouse models in vivo, but conversion using human cells has not yet been demonstrated. Such studies have been difficult to perform since hGPCs are born late during hu

PREVALENCE OF BIOPSY-PROVEN GIANT CELL ARTERITIS IN SOUTHERN SWEDEN

Background: Few previous studies have examined the prevalence of giant cell arteritis (GCA). The main objective of this study is to investigate the prevalence of temporal artery positive GCA (TAB+GCA) in southern Sweden.Methods: The study area is the region of Skåne in southern Sweden with a population of 1,3 million inhabitants (36% aged ⩾50 years). To be included in the study, patient should ful

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents : a prospective cohort study

Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-ra