The relationship between reductions in knee loading and immediate pain response whilst wearing lateral wedged insoles in knee osteoarthritis.

Studies of lateral wedge insoles (LWIs) in medial knee osteoarthritis (OA) have shown reductions in the average external knee adduction moment (EKAM) but no lessening of knee pain. Some treated patients actually experience increases in the EKAM which could explain the overall absence of pain response. We examined whether, in patients with painful medial OA, reductions in the EKAM were associated with lessening of knee pain.

Competition between photodetachment and autodetachment of the 2(1)ππ* state of the green fluorescent protein chromophore anion.

Using a combination of photoelectron spectroscopy measurements and quantum chemistry calculations, we have identified competing electron emission processes that contribute to the 350-315 nm photoelectron spectra of the deprotonated green fluorescent protein chromophore anion, p-hydroxybenzylidene-2,3-dimethylimidazolinone. As well as direct electron detachment from S0, we observe resonant excitation of the 2(1)ππ* state of the anion followed by autodetachment. The experimental photoelectron spectra are found to be significantly broader than photoelectron spectrum calculated using the Franck-Condon method and we attribute this to rapid (∼10 fs) vibrational decoherence, or intramolecular vibrational energy redistribution, within the neutral radical.

Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune-mediated disease.

Objective: Genome-wide association studies (GWAS) have identified genetic variants within multiple risk loci as predisposing to intestinal inflammatory diseases, including Crohn's disease, ulcerative colitis and coeliac disease. Most risk variants affect regulation of transcription, but a critical challenge is to identify which genes and which cell types these variants affect. We aimed to characterise whole transcriptomes for each common T lymphocyte subset resident within the gut mucosa, and use these to infer biological insights and highlight candidate genes of interest within GWAS risk loci.

Factors associated with arthrogenous muscle inhibition in patellofemoral osteoarthritis.

Objectives: Arthrogenous muscle inhibition (AMI) is thought to contribute to quadriceps weakness in knee osteoarthritis (OA), but its relationship with structural changes of bone marrow lesions (BMLs), capsular distension and pain is unclear. This study's objective was to investigate the factors associated with AMI in subjects with symptomatic patellofemoral joint OA (PFJOA).

Design: 126 Subjects with predominant PFJOA were assessed for pain by the visual analogue scale (VAS) for a nominated aggravating activity.

Seasonal variation of acute gastro-intestinal illness by hydroclimatic regime and drinking water source: a retrospective population-based study.

Acute gastro-intestinal illness (AGI) is a major cause of mortality and morbidity worldwide and an important public health problem. Despite the fact that AGI is currently responsible for a huge burden of disease throughout the world, important knowledge gaps exist in terms of its epidemiology. Specifically, an understanding of seasonality and those factors driving seasonal variation remain elusive.

The kinetics and product state distributions from gas-phase reactions of small atomic and molecular cations with C2H4, C2H3F, 1,1-C2H2F2, C2HF3 and C2F4.

The reactions of twenty one gas-phase cations with C2H3F, 1,1-C2H2F2, C2HF3 and C2F4 have been studied in a selected ion flow tube at 298 K. The cations are both atomic and molecular with recombination energies in the range 6-22 eV, and the kinetics and branching ratios into product ions are revealed for all the reactions. These data, together with that from an earlier study of reactions of C(x)F(y)(+) with these four fluorinated ethenes (J.

Personalised medicine and genetic prediction--are we there yet?

A working definition of personalised medicine is the delivery of a tailor-made treatment to the right patient at the right time. How close have recent advances in genetics come to realising this in the clinic?

Evaluating the importance of the carotid chemoreceptors in controlling breathing during exercise in man.

Only the carotid chemoreceptors stimulate breathing during hypoxia in Man. They are also ideally located to warn if the brain's oxygen supply falls, or if hypercapnia occurs. Since their discovery ~80 years ago stimulation, ablation, and recording experiments still leave 3 substantial difficulties in establishing how important the carotid chemoreceptors are in controlling breathing during exercise in Man: (i) they are in the wrong location to measure metabolic rate (but are ideally located to measure any mismatch), (ii) they receive no known signal during exercise linking them with metabolic rate and no overt mismatch signals occur and (iii) their denervation in Man fails to prevent breathing matching metabolic rate in exercise.

Where and how to inject the knee--a systematic review.

Objectives: The knee can be injected at different anatomic sites with or without image-guidance. We undertook a systematic review to determine the accuracy of intra-articular knee injection (IAKI) and whether this varied by site, use of image-guidance, and experience of injectors, and whether accuracy of injection, site, or use of image-guidance influenced outcomes following IAKIs.

Methods: Medline, Embase, AMED, CINAHL, Web of Knowledge, Cochrane Central Registers for Controlled Trials up to Dec 2012 were searched for studies that evaluated either accuracy of IAKIs or outcomes related to accuracy, knee injection sites, or use of image-guidance.

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway.

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis.

Lateral wedge insoles as a conservative treatment for pain in patients with medial knee osteoarthritis: a meta-analysis.

Importance: There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis.

Objective: To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control.

Data Sources: Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language.

Genetic insights into common pathways and complex relationships among immune-mediated diseases.

Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases.

Bond-forming reactions of small triply charged cations with neutral molecules.

Time-of-flight mass spectrometry reveals that atomic and small molecular triply charged cations exhibit extensive bond-forming chemistry, following gas-phase collisions with neutral molecules. These experiments show that at collision energies of a few eV, I(3+) reacts with a variety of small molecules to generate molecular monocations and molecular dications containing iodine. Xe(3+) and CS2(3+) react in a similar manner to I(3+), undergoing bond-forming reactions with neutrals.

Negligible impact of rare autoimmune-locus coding-region variants on missing heritability.

Genome-wide association studies (GWAS) have identified common variants of modest-effect size at hundreds of loci for common autoimmune diseases; however, a substantial fraction of heritability remains unexplained, to which rare variants may contribute. To discover rare variants and test them for association with a phenotype, most studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set. This approach fails to analyse a large fraction of the rare variants present in the entire sample set.

Electron ionisation of sulfur dioxide.

Relative precursor-specific partial ionisation cross sections for the fragment ions formed following electron ionisation of sulfur dioxide (SO2) have been measured for the first time, from 30 to 200 eV, using time-of-flight mass spectrometry coupled with two-dimensional ion coincidence detection. These data quantify the yields of O(2+), O(+), SO(2+), S(+), O2(+), and SO(+) ions, relative to the formation of SO2(+), via single, double, and triple electron ionisation of SO2. Formation of O(2+), following electron-SO2 collisions, has been quantified for the first time.

Screening metal-organic frameworks for selective noble gas adsorption in air: effect of pore size and framework topology.

The adsorption of noble gases and nitrogen by sixteen metal-organic frameworks (MOFs) was investigated using grand canonical Monte Carlo simulation. The MOFs were chosen to represent a variety of net topologies, pore dimensions, and metal centers. Three commercially available MOFs (HKUST-1, AlMIL-53, and ZIF-8) and PCN-14 were also included for comparison.

Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies.

Background & Aims: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies.

DNA methylation analysis in the intestinal epithelium-effect of cell separation on gene expression and methylation profile.

Background: Epigenetic signatures are highly cell type specific. Separation of distinct cell populations is therefore desirable for all epigenetic studies. However, to date little information is available on whether separation protocols might influence epigenetic and/or gene expression signatures and hence might be less beneficial.

A new approach to prevention of knee osteoarthritis: reducing medial load in the contralateral knee.

Objective: Few if any prevention strategies are available for knee osteoarthritis (OA). In those with symptomatic medial OA, the contralateral knee may be at high risk of disease, and a reduction in medial loading in that knee might prevent disease or its progression there. Our aim was to determine how often persons with medial OA on 1 side had either concurrent or later medial OA on the contralateral side, and whether an intervention known to reduce medial loading in affected knees with medial OA might reduce medial loading in the contralateral knee.

Bayesian refinement of association signals for 14 loci in 3 common diseases.

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal.