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Background: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. Methods: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly
Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder occurring predominantly in young women. POTS is characterized by an excessive heart rate increase when assuming upright posture accompanied by symptoms of orthostatic intolerance. The pathophysiology of POTS has not been fully established and is believed to be multifactorial. Purpose We a
Background: 27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear. Methods: Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemist
Background: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild. Objectives: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non–flow-limiting vulnerable plaques. Methods: Three-vessel imaging was performed with a combination intravascular ultraso
Alzheimer's disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer's disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology
In order to identify the signal epitopes of the neuropeptide Y (NPY) molecule, the conformation of the NPY molecule was pertubated by a systematic double D-amino acid replacement of neighbouring residues. These NPY-analogs were examined for receptor affinity and on biological activity. The rat cerebral cortex and hippocampus were used for binding characteristics on Y1 and Y2 binding sites, respect
Genetic factors play an important role in the pathogenesis of osteoporosis but the genes that determine susceptibility to poor bone health are defined incompletely. Previous work has shown that a polymorphism that affects an Spl binding site in the COLIA1 gene is associated with reduced bone mineral density (BMD) and an increased risk of osteoporotic fracture in several populations. Data from cros
Despite long‐standing interest in the evolutionary role of plant hormones, relatively few studies have used hormonally manipulated phenotypes to address questions about phenotypic evolution in plants. In the present investigation, I subjected plants of Crepis tectorum subsp. pumila to simple gibberellin (GA) treatments under both field and greenhouse conditions to assess developmental lability andDespite long‐standing interest in the evolutionary role of plant hormones, relatively few studies have used hormonally manipulated phenotypes to address questions about phenotypic evolution in plants. In the present investigation, I subjected plants of Crepis tectorum subsp. pumila to simple gibberellin (GA) treatments under both field and greenhouse conditions to assess developmental lability and
The southern section of the Mylonite Zone (MZ) is a major lithotectonic terrane boundary in the SW Baltic Shield. It separates the parautochthonous Eastern Segment of the Sveconorwegian orogen from the allochthonous Western Segment. Complex zircons in migmatised and banded orthogneisses along the southern MZ were investigated by ion microprobe analyses guided by backscattered electron imaging to d
BACKGROUND: Sacroiliac joint pain is increasingly recognized as a cause of low back pain. We compared the safety and effectiveness of minimally invasive sacroiliac joint arthrodesis using triangular titanium implants and conservative management in patients with chronic sacroiliac joint pain. METHODS: This study was a prospective, multicenter randomized controlled trial of adults with chronic sacro
Background: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. Methods: In the
Objective: To determine the role of inflammatory biomarkers at 2 years post–anterior cruciate ligament (ACL) injury to predict radiographic knee osteoarthritis (OA) and magnetic resonance imaging (MRI)–defined knee OA at 5 years postinjury, with a secondary aim of estimating the concordance of inflammatory biomarkers assessed by MRI and synovial fluid (SF) analysis. Methods: We studied 113 patient
Objective: To investigate the causal role of cardiometabolic risk factors in osteoarthritis (OA) using associated genetic variants. Methods: We studied 27,691 adults from the Malmö Diet and Cancer Study (MDCS) and replicated novel findings among 376,435 adults from the UK Biobank. Trait-specific polygenic risk scores for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol
The incidence of narcolepsy type 1 (NT1) increased in Sweden following the 2009-2010 mass-vaccination with the influenza Pandemrix-vaccine. NT1 has been associated with Human leukocyte antigen (HLA) DQB1*06:02 but full high-resolution HLA-typing of all loci in vaccine-induced NT1 remains to be done. Therefore, here we performed HLA typing by sequencing HLA-DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1
Background The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group). Methods This analysis studied
OBJECTIVES: the purpose of this study was to assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure and atrial fibrillation, and the added benefit of multiple biomarkers reflecting diverse pathophysiological pathways. BACKGROUND: heart failure and atrial fibrillation are interrelated cardiac diseases associated with substantial morbidity and mortality
The structural heterogeneity of tumor tissue can be probed by diffusion MRI (dMRI) in terms of the variance of apparent diffusivities within a voxel. However, the link between the diffusional variance and the tissue heterogeneity is not well-established. To investigate this link we test the hypothesis that diffusional variance, caused by microscopic anisotropy and isotropic heterogeneity, is assoc
IMPORTANCE Fluid overload occurring as a consequence of overly aggressive fluid resuscitation may adversely affect outcome in hemodynamically unstable critically ill patients. Therefore, following the initial fluid resuscitation, it is important to identify which patients will benefit from further fluid administration. OBJECTIVE To identify predictors of fluid responsiveness in hemodynamically uns
