Psychological Impact of Significantly Short Stature

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142466/1/apa199180s37714.pd

Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254)

INTRODUCTION: Acute trauma involving the anterior cruciate ligament is believed to be a major risk factor for the development of post-traumatic osteoarthritis 10 to 20 years post-injury. In this study, to better understand the early biological changes which occur after acute injury, we investigated synovial fluid and serum biomarkers. METHODS: We collected serum from 11 patients without pre-existing osteoarthritis from a pilot intervention trial (5 placebo and 6 drug treated) using an intra-articular interleukin-1 receptor antagonist (IL-1Ra) therapy, 9 of which also supplied matched synovial fluid samples at presentation to the clinic after acute knee injury (mean 15.2 ± 7.2 days) and at the follow-up visit for reconstructive surgery (mean 47.6 ± 12.4 days). To exclude patients with pre-existing osteoarthritis (OA), the study was limited to individuals younger than 40 years of age (mean 23 ± 3.5) with no prior history of joint symptoms or trauma. We profiled a total of 21 biomarkers; 20 biomarkers in synovial fluid and 13 in serum with 12 biomarkers measured in both fluids. Biomarkers analyzed in this study were found to be independent of treatment (P > 0.05) as measured by Mann-Whitney and two-way ANOVA. RESULTS: We observed significant decreases in synovial fluid (sf) biomarker concentrations from baseline to follow-up for (sf)C-Reactive protein (CRP) (P = 0.039), (sf)lubricin (P = 0.008) and the proteoglycan biomarkers: (sf)Glycosaminoglycan (GAG) (P = 0.019), and (sf)Alanine-Arginine-Glycine-Serine (ARGS) aggrecan (P = 0.004). In contrast, we observed significant increases in the collagen biomarkers: (sf)C-terminal crosslinked telopeptide type II collagen (CTxII) (P = 0.012), (sf)C1,2C (P = 0.039), (sf)C-terminal crosslinked telopeptide type I collagen (CTxI) (P = 0.004), and (sf)N-terminal telopeptides of type I collagen (NTx) (P = 0.008). The concentrations of seven biomarkers were significantly higher in synovial fluid than serum suggesting release from the signal knee: IL-1β (P < 0.0001), fetal aggrecan FA846 (P = 0.0001), CTxI (P = 0.0002), NTx (P = 0.012), osteocalcin (P = 0.012), Cartilage oligomeric matrix protein (COMP) (P = 0.0001) and matrix metalloproteinase (MMP)-3 (P = 0.0001). For these seven biomarkers we found significant correlations between the serum and synovial fluid concentrations for only CTxI (P = 0.0002), NTx (P < 0.0001), osteocalcin (P = 0.0002) and MMP-3 (P = 0.038). CONCLUSIONS: These data strongly suggest that the biology after acute injury reflects that seen in cartilage explant models stimulated with pro-inflammatory cytokines, which are characterized by an initial wave of proteoglycan loss followed by subsequent collagen loss. As the rise of collagen biomarkers in synovial fluid occurs within the first month after injury, and as collagen loss is thought to be irreversible, very early treatment with agents to either reduce inflammation and/or reduce collagen loss may have the potential to reduce the onset of future post-traumatic osteoarthritis. TRIAL REGISTRATION: The samples used in this study were derived from a clinical trial NCT00332254 registered with ClinicalTrial.gov

First Qualification Study of Serum Biomarkers as Indicators of Total Body Burden of Osteoarthritis

BACKGROUND: Osteoarthritis (OA) is a debilitating chronic multijoint disease of global proportions. OA presence and severity is usually documented by x-ray imaging but whole body imaging is impractical due to radiation exposure, time and cost. Systemic (serum or urine) biomarkers offer a potential alternative method of quantifying total body burden of disease but no OA-related biomarker has ever been stringently qualified to determine the feasibility of this approach. The goal of this study was to evaluate the ability of three OA-related biomarkers to predict various forms or subspecies of OA and total body burden of disease. METHODOLOGY/PRINCIPAL FINDINGS: Female participants (461) with clinical hand OA underwent radiography of hands, hips, knees and lumbar spine; x-rays were comprehensively scored for OA features of osteophyte and joint space narrowing. Three OA-related biomarkers, serum hyaluronan (sHA), cartilage oligomeric matrix protein (sCOMP), and urinary C-telopeptide of type II collagen (uCTX2), were measured by ELISA. sHA, sCOMP and uCTX2 correlated positively with total osteophyte burden in models accounting for demographics (age, weight, height): R(2) = 0.60, R(2) = 0.47, R(2) = 0.51 (all p<10(-6)); sCOMP correlated negatively with total joint space narrowing burden: R(2) = 0.69 (p<10(-6)). Biomarkers and demographics predicted 35-38% of variance in total burden of OA (total joint space narrowing or osteophyte). Joint size did not determine the contribution to the systemic biomarker concentration. Biomarker correlation with disease in the lumbar spine resembled that in the rest of the skeleton. CONCLUSIONS/SIGNIFICANCE: We have suspected that the correlation of systemic biomarkers with disease has been hampered by the inability to fully phenotype the burden of OA in a patient. These results confirm the hypothesis, revealed upon adequate patient phenotyping, that systemic joint tissue concentrations of several biomarkers can be quantitative indicators of specific subspecies of OA and of total body burden of disease

Follicle-stimulating Hormone is Independently Associated with Lean Mass but not BMD in Younger Postmenopausal Women

PURPOSE: Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.METHODS: We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT).RESULTS: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β=-0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD.CONCLUSIONS: After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight

Interference in Exclusive Vector Meson Production in Heavy Ion Collisions

Photons emitted from the electromagnetic fields of relativistic heavy ions can fluctuate into quark anti-quark pairs and scatter from a target nucleus, emerging as vector mesons. These coherent interactions are identifiable by final states consisting of the two nuclei and a vector meson with a small transverse momentum. The emitters and targets can switch roles, and the two possibilities are indistinguishable, so interference may occur. Vector mesons are negative parity so the amplitudes have opposite signs. When the meson transverse wavelength is larger than the impact parameter, the interference is large and destructive. The short-lived vector mesons decay before amplitudes from the two sources can overlap, and so cannot interfere directly. However, the decay products are emitted in an entangled state, and the interference depends on observing the complete final state. The non-local wave function is an example of the Einstein-Podolsky-Rosen paradox.Comment: 13 pages with 3 figures; submitted to Physical Review Letter

Geometric representations for minimalist grammars

We reformulate minimalist grammars as partial functions on term algebras for strings and trees. Using filler/role bindings and tensor product representations, we construct homomorphisms for these data structures into geometric vector spaces. We prove that the structure-building functions as well as simple processors for minimalist languages can be realized by piecewise linear operators in representation space. We also propose harmony, i.e. the distance of an intermediate processing step from the final well-formed state in representation space, as a measure of processing complexity. Finally, we illustrate our findings by means of two particular arithmetic and fractal representations.Comment: 43 pages, 4 figure

Separated at Birth? Microarray Analysis of Two Strikingly Similar Yersinia Species

This is the final version of the article. Available from [publisher] via the DOI in this record.--We acknowledge financial support for this project from DSTL and The Wellcome Trust. We also acknowledge BµG@S (the Bacterial Microarray Group at St George’s) and The Wellcome Trust for funding their work; Keith Vass from the University of Glasgow; and Mike Prentice from St. Bartholomew’s Hospital for his advice and expertise in all things Yersinia

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Interpretation of serum C-reactive protein (CRP) levels for cardiovascular disease risk is complicated by race, pulmonary disease, body mass index, gender, and osteoarthritis

High sensitivity serum C-reactive protein (hsCRP) is used as a marker of risk for cardiovascular disease (CVD); however CRP is a non-specific acute phase reactant. We evaluated the association between hsCRP concentrations and the most common form of arthritis, osteoarthritis (OA), and assessed the applicability of hsCRP for CVD risk prediction