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Protein synthesis of the pro-inflammatory S100A8/A9 complex in plasmacytoid dendritic cells and cell surface S100A8/A9 on leukocyte subpopulations in systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in many different organ systems, activation of leukocytes and production of pro-inflammatory cytokines. The heterodimer of the cytosolic calcium-binding proteins S100A8 and S100A9 (S100A8/A9) is secreted by activated polymorphonuclear neutrophils (PMNs) and monocytes and serves as a seru

Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical trials using a multi-biomarker disease activity score as an inclusion criterion.

Objective Rheumatoid arthritis (RA) clinical trials often exclude patients with low C-reactive protein (CRP), slowing trial enrollment. We evaluated whether RA patients with a high multi-biomarker disease activity (MBDA) score (>44) among those with low CRP (≤10 mg/L) could complement patients with CRP >10mg/L to enhance patient recruitment without affecting clinical trial outcomes. Methods We eva

Incidence of Cancer in Patients With Schizophrenia and Their First-Degree Relatives: A Population-Based Study in Sweden.

Context: Previous studies of the association between schizophrenia and cancer have produced conflicting results, probably because of the failure to control for confounding factors. Objective: To test if the possible association between schizophrenia and cancer is genetic by investigating the incidence of cancer in patients with schizophrenia and their relatives. Design: Retrospective cohort stud

Triparental Families: A New Genetic-Epidemiological Design Applied to Drug Abuse, Alcohol Use Disorders, and Criminal Behavior in a Swedish National Sample.

Objective: The authors sought to clarify the sources of parent-offspring resemblance for drug abuse, alcohol use disorders, and criminal behavior, using a novel genetic-epidemiological design. Method: Using national registries, the authors identified rates of drug abuse, alcohol use disorders, and criminal behavior in 41,360 Swedish individuals born between 1960 and 1990 and raised in triparental

Quality of Life and the Effect of Memantine in Dementia with Lewy Bodies and Parkinson's Disease Dementia.

Aim: To investigate quality of life (QOL) and the effect of memantine treatment in patients with Lewy body dementias. Methods: A secondary analysis of a randomized controlled study in 70 patients with Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB) over 24 weeks using caregiver-rated QOL-Alzheimer's disease (AD) in domains according to the WHO's classification of health. Resu

Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors

Objective To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis. Methods. Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated

The impact of low-frequency and rare variants on lipid levels.

Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs w

Nonablative neonatal bone marrow transplantation rapidly reverses severe murine osteopetrosis despite low level engraftment and lack of selective expansion of the osteoclastic lineage.

Infantile malignant osteopetrosis (IMO) is caused by lack of functional osteoclasts leading to skeletal abnormalities, blindness due to compression of the optic nerves, bone marrow (BM) failure and early death. In most patients TCIRG1, a proton pump subunit essential for bone resorption, is mutated. Oc/oc mice represent a model for IMO due to a deletion in Tcirg1 and die around 4 weeks. To determi

The impact of type 2 diabetes mellitus on cancer-specific survival: A follow-up study in sweden.

BACKGROUND: Earlier studies have suggested that type 2 diabetes mellitus (T2DM) alters the risk of developing a variety of cancers, but little has been known about the impact of T2DM on cancer prognosis. On the basis of nationwide population-based Swedish registries, the authors of this report compared the cause-specific survival among cancer patients with and without T2DM. METHODS: Patients with

Factors associated with prospective development of environmental annoyance

Objectives: Idiopathic environmental intolerance (IEI) has in cross-sectional studies been associated with emotional problems and psychiatric disorders. However, in the absence of prospective studies it has not been possible to determine whether emotional problems precede the onset of IEI, or are a consequence of IEI. The purpose of this study was to address this issue in a prospective panel study

Efficient Ablation of Genes in Human Hematopoietic Stem and Effector Cells using CRISPR/Cas9.

Genome editing via CRISPR/Cas9 has rapidly become the tool of choice by virtue of its efficacy and ease of use. However, CRISPR/Cas9-mediated genome editing in clinically relevant human somatic cells remains untested. Here, we report CRISPR/Cas9 targeting of two clinically relevant genes, B2M and CCR5, in primary human CD4(+) T cells and CD34(+) hematopoietic stem and progenitor cells (HSPCs). Use

Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions

Objective: Whether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung. Methods: Bronchial and transbronchi

Acinar ventilation heterogeneity in COPD relates to diffusion capacity, resistance and reactance.

The aim of this study was to investigate heterogenic ventilation in the acinar (Sacin) and conductive (Scond) airways of patients with varying chronic obstructive pulmonary disease (COPD) severity and how these relates to advanced lung function parameters, primarily measured by impulse oscillometry (IOS). A secondary aim was to investigate the effects of a short acting beta2-agonist and a muscarin

A Common SCN5A Variant Is Associated with PR Interval and Atrial Fibrillation Among African Americans

rs7629265 and AF Risk ObjectiveWe examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans. BackgroundThe SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger populati

Emergence of NK cell progenitors and functionally competent NK cell lineage subsets in the early mouse embryo.

The earliest stages of natural killer (NK) cell development are not well characterized. In this study, we investigated in different fetal hematopoietic tissues how NK cell progenitors and their mature NK cell progeny emerge and expand during fetal development. Here we demonstrate, for the first time, that the counterpart of adult bone marrow Lin(-)CD122(+)NK1.1(-)DX5(-) NK cell progenitor (NKP) em