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Presymptomatic autoantibodies in Sjögren's syndrome: what significance do they hold for the clinic?

In a number of autoimmune diseases, for example, rheumatoid arthritis and systemic lupus erythematosus, it is known that autoantibodies are present before the clinical onset. Recently we have shown that autoantibodies can be found many years before symptom onset in primary Sjögren's syndrome. This implies that screening for autoantibodies may be used to identify individuals at risk of developing s

Increased aldehyde-modification of collagen type IV in symptomatic plaques - A possible cause of endothelial dysfunction.

Subendothelial LDL-adhesion and its subsequent oxidation are considered as key events in the development of atherosclerotic lesions. During oxidation of LDL, reactive aldehydes such as malondialdehyde (MDA) are formed, which modify apolipoprotein B100. However, the possibility that these reactive aldehydes could leak out of the LDL-particle and modify surrounding extracellular matrix proteins has

Serial soluble neurofilament heavy chain in plasma as a marker of brain injury after cardiac arrest

Introduction: Induced hypothermia has been shown to improve outcome after cardiac arrest, but early prognostication is hampered by the need for sedation. Here we tested whether a biomarker for neurodegeneration, the neurofilament heavy chain (NfH), may improve diagnostic accuracy in the first days after cardiac arrest. Methods: This prospective study included 90 consecutive patients treated with h

Regulated protein aggregation, a mechanism to control the activity of the ClpXP adaptor protein YjbH.

Bacteria use stress response pathways to activate diverse target genes to react to a variety of stresses. The Bacillus subtilis Spx protein is a global transcriptional regulator that controls expression of more than 140 genes and operons in response to thiol-specific oxidative stress. Under non-stress conditions the concentration of Spx is kept low by proteolysis catalyzed by the ClpXP complex. Sp

Signatures of mutational processes in human cancer

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in

Study of the uptake of non-steroid anti-inflammatory drugs in wheat and soybean after application of sewage sludge as a fertilizer

Non-steroid anti-inflammatory drugs (NSAIDs) are frequently occurring in sludge and waters from sewage treatment plants (STPs). Sludge obtained from sewage treatment is often applied as a fertilizer in agriculture and not many studies about the uptake of pharmaceuticals into crops can be found. In this paper, we present a greenhouse experiment to study the presence of four NSAIDs (naproxen, ketopr

Temperature, size, reproductive allocation, and life-history evolution in a gregarious caterpillar

The present study aimed to investigate the relationship between growth rate, final mass, and larval development, as well as how this relationship influences reproductive trade-offs, in the context of a gregarious life-style and the need to keep an optimal group size. We use as a model two sympatric populations of the pine processionary moth Thaumetopoea pityocampa, which occur in different seasons

Is there a future in glycerol as a feedstock in the production of biofuels and biochemicals?

Glycerine is a chemical with a wide variety of uses. There are over 2000 known applications in cosmetics, foodstuffs, fi ne chemicals, and other industries. With the recent boom for liquid biofuels however, glycerine – which is a by-product mainly of biodiesel production – has become abundant. New uses for the chemical are being researched, but little attention has been paid to the production and

Balloon Kyphoplasty for the Treatment of Acute Vertebral Compression Fractures: 2-Year Results From a Randomized Trial

Vertebral fractures are often painful and lead to reduced quality of life and disability. We compared the efficacy and safety of balloon kyphoplasty to nonsurgical therapy over 24 months in patients with acute painful fractures. Adults with one to three vertebral fractures were randomized within 3 months from onset of pain to undergo kyphoplasty (n = 149) or nonsurgical therapy (n = 151). Quality

Transient Access to the Protein Interior: Simulation versus NMR.

Many proteins rely on rare structural fluctuations for their function, whereby solvent and other small molecules gain transient access to internal cavities. In magnetic relaxation dispersion (MRD) experiments, water molecules buried in such cavities are used as intrinsic probes of the intermittent protein motions that govern their exchange with external solvent. While this has allowed a detailed c

Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study

ObjectiveA subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). MethodsPatients received lenalidomide 10mg/d (days 1-21; n=47) or 5mg/d (days 1-28; n=43) on 28-d cycles or placebo (n=45). From the placebo and lenalid

Process engineering for bioflavour production with metabolically active yeast - a minireview.

Flavours are biologically active molecules of large commercial interest in the food, cosmetics, detergent and pharmaceutical industry. The production of flavours can take place by either extraction from plant materials, chemical synthesis, through biological conversion of precursor molecules or through de novo biosynthesis. The latter alternatives are gaining importance through the rapidly growing

Hybrid Iterative Reconstruction Algorithm Improves Image Quality in Craniocervical CT Angiography.

OBJECTIVE. The purpose of this study was to evaluate the potential of a hybrid iterative reconstruction algorithm for improving image quality in craniocervical CT angiography (CTA) and to assess observer performance. SUBJECTS AND METHODS. Thirty patients (mean age, 58 years; range 16-80 years) underwent standard craniocervical CTA (volume CT dose index, 6.8 mGy, 2.8 mSv). Images were reconstructed

Audio spectrum analysis of umbilical artery Doppler ultrasound signals applied to a clinical material.

Analysis of umbilical artery flow velocity waveforms characterized by pulsatility index (PI) is used to evaluate fetoplacental circulation in high-risk pregnancies. However, an experienced sonographer may be able to further differentiate between various timbres of Doppler audio signals. Recently, we have developed a method for objective audio signal characterization; the method has been tested in

The mediating role of acceptance in multidisciplinary cognitive behavioral therapy for chronic pain

Cognitive Behavioral Therapy (CBT) is the most frequently delivered psychological intervention for adults with chronic pain. The treatment yields modest effect sizes and the mechanisms of action remain understudied and unclear. Efforts are needed to identify treatment mediators that could be used to refine CBT and improve outcomes. The primary aim of this study is to investigate whether pain-relat

Understanding the Molecular Activity of Alkaline Sphingomyelinase (NPP7) by Computer Modeling

The enzymes in the nucleotide pyrophosphatase/phosphodiesterase (NPP) family have various substrates such as nucleotides, phospholipids, and sphingolipids. The substrate specificity in relation to their structures is largely unknown because no mammalian NPP complex has been crystallized. NPP7, also called alkaline sphingomyelinase (alk-SMase), is a NPP family member that may have important implica

Synthesis of Substituted Oxazoles from N-Benzyl Propargyl Amines and Acid Chlorides

The reaction between N-benzylpropargylamines and acid chlorides at elevated temperatures provides efficient, direct access to a variety of di- and tri-substituted oxazoles. The versatility of this reaction is explored and 21 examples are demonstrated. The usefulness of the methodology is showcased through the short and efficient formal syntheses of medicinally relevant drugs aleglitazar and romaza