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UNLABELLED: To clarify the role of the TNFRSF11B gene encoding osteoprotegerin (OPG), in Paget's disease of bone (PDB) we studied TNFRSF11B polymorphisms in an association study of 690 UK subjects and in a worldwide familial study of 66 kindreds. We found that the G1181 allele of TNFRSF11B, encoding lysine at codon 3 of the OPG protein, predisposes to both sporadic and familial PDB.INTRODUCTION: P
BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein.METHODS: We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction-based assay. We the
AIM: A survival benefit has been observed for colorectal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). However, this treatment modality is associated with a considerable morbidity and mortality and in a significant number of patients survival is not improved. We studied whether poor survivors c
BACKGROUND: Malignant pleural mesothelioma (MPM) is a disease mostly confined to the thoracic cavity. Untreated, the median survival is <1 year. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy is used to kill residual tumor cells on the surface of the thoracic cavity while having limited systemic side effects.METHODS: From August 1998 to August 2001, 22 p
INTRODUCTION: It is unclear how different proteinopathies (tau, transactive response DNA-binding protein 43 [TDP-43], amyloid β [Aβ], and α-synuclein) contribute to atrophy within medial temporal lobe (MTL) subregions in Alzheimer's disease (AD).METHODS: We utilized antemortem structural magnetic resonance imaging (MRI) data to measure MTL substructures and examined the relative contribution of ta
Hepatic failure is an important risk factor for poor outcome in septic patients. Using a chemical tagging workflow and high-resolution mass spectrometry, we demonstrate that rapid proteome remodeling of the vascular surfaces precedes hepatic damage in a murine model of Staphylococcus aureus sepsis. These early changes include vascular deposition of neutrophil-derived proteins, shedding of vascular
Esophageal perforation is associated with significant mortality, and this may markedly increase with advanced age. This multicenter study investigates this issue in patients older than 80 years. Data on 33 patients >80 years old who underwent conservative (10 patients), endoclip (one patient), stent grafting (11 patients), or surgical treatment (11 patients) for esophageal perforation were collect
OBJECT: Central nervous system axons regenerate poorly after traumatic brain injury (TBI), partly due to inhibitors such as the protein Nogo-A present in myelin. The authors evaluated the efficacy of anti-Nogo-A monoclonal antibody (mAb) 7B12 administration on the neurobehavioral and cognitive outcome of rats following lateral fluid-percussion brain injury, characterized the penetration of the 7B1
Background and purpose - Little is know about patterns of sick leave in connection with total hip and knee joint replacement (THR and TKR) in patients with osteoarthritis (OA). Patients and methods - Using registers from southern Sweden, we identified hip and knee OA patients aged 40-59 years who had a THR or TKR in the period 2004-2012. Patients who died or started on disability pension were excl
The current downturn of the arctic cryosphere, such as the strong loss of sea ice, melting of ice sheets and glaciers, and permafrost thaw, affects the marine and terrestrial carbon cycles in numerous interconnected ways. Nonetheless, processes in the ocean and on land have been too often considered in isolation while it has become increasingly clear that the two environments are strongly connecte
Non-invasive imaging biomarkers (IBs) are warranted to enable improved diagnostics and follow-up monitoring of interstitial lung disease (ILD) including drug-induced ILD (DIILD). Of special interest are IB, which can characterize and differentiate acute inflammation from fibrosis. The aim of the present study was to evaluate a PET-tracer specific for Collagen-I, combined with multi-echo MRI, in a
Optimal maternal long chain polyunsaturated fatty acid (LCPUFA) status is essential for the developing foetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS single nucleotide polymorphisms (SNPs) have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), a
Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we f
BackgroundRight ventricular (RV) function is a major determinant of outcome in patients with pulmonary hypertension. Cardiac magnetic resonance (CMR) is gold standard to assess RV ejection fraction (RVEFCMR), however this is a crude measure. New CMR measures of RV function beyond RVEFCMR have emerged, such as RV lateral atrio-ventricular plane displacement (AVPDlat), maximum emptying velocity (S’C
Proteolytic activation is a unique feature of the epithelial sodium channel (ENaC). However, the underlying molecular mechanisms and the physiologically relevant proteases remain to be identified. The serine protease trypsin I can activate ENaC in vitro but is unlikely to be the physiologically relevant activating protease in ENaC-expressing tissues in vivo. Herein, we investigated whether human t
OBJECTIVE: Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies. METHODS AND RESULTS: We tested whether combinations
We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis.
Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1-10 nM) and high (10 muM) concentrations of forskolin, respectively. The expression of GLP-1 receptors in alpha cells is <0.2% of that in beta cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose indep
OBJECTIVE: To determine whether musculoskeletal pain was associated with impaired sexual function in a population sample of middle-aged and older men. METHODS: The European Male Ageing Study (EMAS), a multicenter population-based study of men aged 40-79 years, was used to investigate this hypothesis. A questionnaire asked about the presence and duration of musculoskeletal pain, allowing subjects t
BRCA1 and BRCA2 screening in women at high-risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population-based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of wh
