Major human milk oligosaccharides are absorbed into the systemic circulation after oral administration in rats.

Human milk oligosaccharides (HMO) are involved in many biological functions influencing infant health. Although HMO act locally at the intestine, recent evidence has demonstrated that HMO are partially incorporated into the systemic circulation of breast-fed infants. In the last few years, a large amount of research has been conducted using preclinical models to uncover new biological functions of HMO. The aim of this study was to evaluate the absorption and urine excretion of HMO in rats. We administered a single oral dose of the following HMO: 2'-fucosyllactose (2'-FL), 6'-sialyllactose and lacto-N-neotetraose at different concentrations to adult rats. The time course of absorption of HMO into the bloodstream and their appearance in urine was studied. Our results showed that rats, similar to human infants, are able to effectively absorb a portion of HMO from the intestine into plasma and to excrete them in urine. On the basis of this, we also conducted a specific kinetic absorption study with 2'-FL, the most predominant HMO in human milk, in 9-11-d-old rat pups. Our results confirmed that a significant amount of 2'-FL was absorbed into the systemic circulation and subsequently excreted in urine during lactation in rats in a dose-depended manner. We also found basal levels of these HMO in plasma and urine of adult rats as well as rat pups as a natural result of nursing. Our data suggest that the rat may be a useful preclinical model that provides new insights into the metabolism and functions of HMO.

Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.

BACKGROUND: The prebiotic nature of human milk oligosaccharides (HMOs) and increasing evidence of direct immunomodulatory effects of these sugars suggest that they may have some therapeutic potential in allergy. Here, we assess the effect of two HMOs, 2'-fucosyllactose and 6'-sialyllactose, on symptomatology and immune responses in an ovalbumin-sensitized mouse model of food allergy. METHODS: The effects of oral treatment with 2'-fucosyllactose and 6'-sialyllactose on anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in sensitized mice were investigated. Mast cell functions in response to oral HMO treatment were also measured in the passive cutaneous anaphylaxis model, and direct effects on IgE-mediated degranulation of mast cells were assessed. RESULTS: Daily oral treatment with 2'-fucosyllactose or 6'-sialyllactose attenuated food allergy symptoms including diarrhea and hypothermia. Treatment with HMOs also suppressed antigen-induced increases in mouse mast cell protease-1 in serum and mast cell numbers in the intestine. These effects were associated with increases in the CD4(+) CD25(+) IL-10(+) cell populations in the Peyer's patches and mesenteric lymph nodes, while 6'-sialyllactose also induced increased IL-10 and decreased TNF production in antigen-stimulated splenocytes. Both 2'-fucosyllactose and 6'-sialyllactose reduced the passive cutaneous anaphylaxis response, but only 6'-sialyllactose directly inhibited mast cell degranulation in vitro, at high concentrations. CONCLUSIONS: Our results suggest that 2'-fucosyllactose and 6'-sialyllactose reduce the symptoms of food allergy through induction of IL-10(+) T regulatory cells and indirect stabilization of mast cells. Thus, human milk oligosaccharides may have therapeutic potential in allergic disease.

Frequency and spatial distribution of cartilage thickness change in knee osteoarthritis and its relation to clinical and radiographic covariates - data from the osteoarthritis initiative.

OBJECTIVE: Estimate the frequency and spatial location of rapid femorotibial cartilage thinning or thickening in knees with, or at risk of, osteoarthritis (OA) and examine their association with clinical and radiographic covariates. DESIGN: Knee cartilage thickness change over 12 months was measured using magnetic resonance imaging in the right knee of 757 Osteoarthritis Initiative (OAI) participants that had radiographic findings of osteophytes or joint space narrowing (JSN). Thickness changes in individual knees were classified as having rapid thinning or thickening or no detectable OA-related change when compared to asymptomatic OAI Control cohort knees. RESULTS: Cartilage thinning, found in 18.5% of subjects, was more frequent in knees with OAI calculated Kellgren-Lawrence grade (cKLG) > 2 (P < 0.001) and with frequent pain (P = 0.047). No link was found between body mass index, sex, and age and cartilage thinning (P > 0.15). The percent of knees with thickening was small (4.4%), but greater in knees with frequent pain (P = 0.02). Rapid thinning was most common in the central (36.4%) and external (32.1%) subregions of the medial weight-bearing femur. Mean cartilage loss in rapidly thinning subregions ranged from 11.2%/y to 24.6%/y. Knees with cKLG > 2, but classified as having no detectable OA-related change had mean cartilage loss rates significantly >0 (0.4%/y-1.3%/y) in 10 subregions. CONCLUSION: Most observed subregional changes in OA knees were indistinguishable from changes found in an asymptomatic cohort, but a fraction of subregions showed rapid progression. The relative frequency of rapid thinning increases when cKLG > 2, a classification closely associated with JSN and/or frequent knee pain are present.

Direct comparison of fixed flexion, radiography and MRI in knee osteoarthritis: responsiveness data from the Osteoarthritis Initiative.

OBJECTIVE: Minimum radiographic joint space width (mJSW) represents the Food and Drug Administration (FDA) standard for demonstrating structural therapeutic benefits for knee osteoarthritis (KOA), but only shows moderate responsiveness (sensitivity to change). We directly compare the responsiveness of magnetic resonance imaging (MRI)-based cartilage thickness and JSW measures from fixed-flexion radiography (FFR) and explore the correlation of region-matched changes between both methods. METHODS: Nine hundred and sixty-seven knees of Osteoarthritis Initiative participants with radiographic KOA were studied: 445 over 1 year with coronal FLASH MRI and FFR, and 375/522 over 1/2 years with sagittal DESS MRI and FFR. Standardized response means (SRM) of cartilage thickness and mJSW were compared using the sign-test. RESULTS: With FLASH MRI, SRM was -0.28 for medial femorotibial compartment (MFTC) cartilage loss vs -0.15 for mJSW, and -0.32 vs -0.22 for the most sensitive MRI subregion (central MFTC) vs the most sensitive fixed-location JSW(x = 0.25). With DESS MRI, 1-year SRM was -0.34 for MFTC vs -0.22 for mJSW and -0.44 vs -0.28 for central MFTC vs JSW(x = 0.225). Over 2 years, the SRM was significantly greater for MFTC than for mJSW (-0.43 vs -0.31, P = 0.017) and for central MFTC than for JSW(x = 0.225) (-0.51 vs -0.44, P < 0.001). Correlations between changes in spatially matched MRI subregions and fixed-location JSW were not consistently higher (r = 0.10-0.51) than those between non-matched locations (r = 0.15-0.50). CONCLUSIONS: MRI displays greater responsiveness in KOA than JSW FFR-based JSW, with the greatest SRM observed in the central medial femorotibial compartment. Fixed-location radiographic measures appear not capable of determining the spatial distribution of femorotibial cartilage loss.

Ketamine-medetomidine compared to tiletamine-zolazepam-medetomidine for immobilisation of semi-captive cheetahs (Acinonyx jubatus).

ABSTRACT: The immobilisation time and cardiopulmonary effects of ketamine-medetomidine (KM) and tiletamine-zolazepam-medetomidine (TZM) were compared in semi-captive cheetahs (Acinonyx jubatus). Seven healthy adult cheetahs were included in a randomised prospective crossover study. Each cheetah was immobilised on two occasions by remote injection, once with a combination of ketamine (4.93 ± 0.75 mg/kg) and medetomidine (0.038 ± 0.003 mg/kg) (KM) and once with tiletamine-zolazepam (1.16 ± 0.12 mg/kg) and medetomidine (0.039 ± 0.002 mg/kg) (TZM). Time to safe approach, characterised by absent responses to an ear flick and tail tug, was recorded as the immobilisation time. Following immobilisation, cardiopulmonary parameters were recorded, and an arterial blood gas sample analysed. Data is reported as mean ± SD and compared using a general linear mixed model (p < 0.05). Immobilisation times were no different between combinations, 11.4 ± 5.7 minutes for KM and 13.2 ± 4.6 minutes for TZM (p = 0.528). Systolic blood pressure was 218 ± 22 mmHg for KM and 210 ± 28 mmHg for TZM (p = 0.594). There was moderate hypoxaemia with both combinations with arterial oxygen partial pressure of 58.4 ± 6.6 mmHg for KM and 61.3 ± 4.2 mmHg for TZM (p = 0.368). Haematocrit was higher with KM (40.7 ± 2.5) than TZM (35.8 ± 2.8, p = 0.007). There were differences in electrolytes, with TZM resulting in higher serum potassium (4.3 ± 0.2 mmol/L, p < 0.001) and glucose (11.8 ± 2.9 mmol/L, p = 0.039) than KM. Both combinations provided acceptable immobilisation for field use, although severe hypertension was a consistent finding. Supplementation with oxygen is recommended with both combinations.

Clinical, radiographic, molecular and MRI-based predictors of cartilage loss in knee osteoarthritis.

OBJECTIVE: To examine the relationship of baseline clinical, radiographic, molecular and MRI measures with structural progression (subregional MRI-based femorotibial cartilage loss) in knee osteoarthritis (OA). METHODS: Single knees of 75 female participants with radiographic knee OA (and 77 healthy control participants) were examined over 24 months using MRI. Subregional femorotibial cartilage thickness was determined at baseline and follow-up. Baseline clinical, radiographic, molecular (n=16) and quantitative MRI-based measures of the meniscus and cartilage, including delayed gadolinium-enhanced MRI (dGEMRIC) and T2, were obtained. Differences in these baseline measures between radiographic osteoarthritic knees with longitudinal cartilage thinning (or thickening) and those with no significant change were evaluated by receiver operator characteristic analyses and Wilcoxon rank sum tests. RESULTS: The relatively strongest predictors of longitudinal cartilage thinning were reduced baseline cartilage thickness in the medial femur (area under the curve (AUC)=0.81), varus malalignment (AUC=0.77), reduced minimum joint space width and a greater radiographic joint space narrowing (JSN) score (both AUC=0.74). These remained significant after adjusting for multiple comparisons using false discovery rates. Reduced bone resorption (C-terminal telopeptide of type I collagen; AUC=0.65) and a low dGEMRIC index (reflecting low proteoglycan content) in the medial tibia (AUC=0.68) were associated with longitudinal cartilage thinning, but failed to reach statistical significance after correction for multiple testing in this (small) sample. CONCLUSIONS: This exploratory study indicates that baseline molecular or MRI cartilage compositional markers may not provide better discrimination between knees with cartilage thinning and those without longitudinal change than simple radiographic measures, such as greater JSN score.

Using ordered values of subregional cartilage thickness change increases sensitivity in detecting risk factors for osteoarthritis progression.

OBJECTIVE: To examine whether ordered values of (sub)regional femorotibial cartilage thickness change are superior to region-based approaches in detecting risk factors for cartilage loss in osteoarthritis (OA). METHODS: 58 women with knee OA had 3 Tesla MR images acquired at baseline and 24 months. Changes in cartilage thickness (∆ThCtAB) were determined in eight medial femorotibial subregions. An ascending sort of individual ∆ThCtAB measurements was done to create "ordered values". Risk factors for cartilage loss considered were: age, BMI, anatomical knee axis (AAA), minimal (medial) joint space width (mJSW), and percent of medial tibial plateau covered by the meniscus (percent cover). All change metrics were tested for association with the risk factors using Kendall's τ and relative sensitivity of multiple tests of subregions and ordered values were compared with single metrics of change from plate and compartment summaries and the first ordered value. RESULTS: The associations between subregion ∆ThCtAB and AAA (P=0.0002), mJSW (P=0.016), and age (P=0.011) were significant, but only AAA (at α=0.05) and age (at α=0.1) remained significant after adjusting for multiple subregions. In contrast, cMFTC had P-values<0.05 for AAA (P=0.0001), mJSW (P=0.016), and meniscus subluxation (0.04). The first ordered value had significant associations with AAA (P=0.0004), mJSW (P=0.003), meniscus subluxation (P=0.02) and percent cover (P=0.031) all of which were significant at α=0.05 after adjusting for tests on multiple risk factors. CONCLUSION: Ordered values of ∆ThCtAB were more sensitive in detecting risk factors of cartilage loss than subregional ∆ThCtAB. Sensitivity was further enhanced by considering the minimum ordered value as a single test, thus not requiring adjustment for multiple tests. Using ordered values there was a significant association between ∆ThCtAB and baseline AAA, mJSW, meniscus subluxation and meniscus percent cover. This study provides an important step in validating ordered values of cartilage change.

MRI-based extended ordered values more efficiently differentiate cartilage loss in knees with and without joint space narrowing than region-specific approaches using MRI or radiography--data from the OA initiative.

OBJECTIVE: The sensitivity to change of quantitative analysis of cartilage in knee osteoarthritis using magnetic resonance imaging (MRI) is compromised by the spatial heterogeneity of cartilage loss. We explore whether extended (medial-lateral) "ordered values" (OVs) are superior to conventional approaches of analyzing subregional cartilage thickness loss and to radiography, in differentiating rates of progression in knees with and without joint space narrowing (JSN). METHODS: 607 Osteoarthritis Initiative (OAI) participants (308 without and 299 with baseline JSN at baseline) were studied over 12 months. Subregional femorotibial cartilage loss was determined in all knees, and changes in minimum joint space width (mJSW) in a subset of 290 knees. Subregional thickness changes in medial and lateral tibial and femoral cartilages were sorted in ascending order (OV1-16). A Wilcoxon rank-sum test was used to compare rates of change in knees with and without JSN. RESULTS: JSN-knees displayed greater cartilage loss than those without JSN, with minimal P-values of 0.008 for femorotibial subregions, 3.3×10(-4) for medial OV1, and 5.4×10(-7) for extended (medial and lateral) OV1. mJSW measurements (n=290) did not discriminate between longitudinal rates of change in JSN vs no-JSN knees (P=0.386), whereas medial OV1 (P=5.1×10(-4)) and extended OV1 did (P=2.1×10(-5)). CONCLUSION: Extended OVs showed higher sensitivity to detecting differences in longitudinal rates of cartilage loss in knees with and without baseline JSN than anatomical (sub)regions and radiography. The OV technique also circumvents challenges of selecting particular regions "a priori" in clinical trials and may thus provide a powerful tool in studying risk factors or treatment efficacy in osteoarthritis.

Impacts on work performance; what matters 6 months on?

BACKGROUND: Presenteeism often precedes and follows a period of work absence. Cross-sectional analysis of a workforce survey highlighted health, psychosocial and work characteristics as being particularly important in understanding current work performance, but it is unclear whether these variables predict future work performance. AIMS: To establish whether self-reported health, perceptions of work and objective characteristics of work measured at baseline can predict performance at 6 months follow-up. METHODS: Self-completed questionnaires to assess health, objective characteristics of work and perceptions of work were completed at two public sector organizations. Follow-up questionnaires were completed at 6 months to assess workplace performance using a visual analogue scale for self-rated performance and the Stanford Presenteeism Scale 6 (SPS6). RESULTS: Five hundred and five employees completed questionnaires at baseline and 310 (61%) of these completed follow-up questionnaires. Psychological distress as measured with the General Health Questionnaire and perceptions of work predicted both self-rated performance and SPS6 score. Objective characteristics of work were relatively unimportant in the prediction of future performance. CONCLUSIONS: This study has provided an initial indication of the factors that may predict performance at follow-up in the population studied. These findings may be used to generate hypotheses for future studies and highlights the need to assess a range of factors in relation to an individual's performance at work including health and perceptions of work.

Change in regional cartilage morphology and joint space width in osteoarthritis participants versus healthy controls: a multicentre study using 3.0 Tesla MRI and Lyon-Schuss radiography.

OBJECTIVE: Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls. METHODS: A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren-Lawrence grade (KLG)2 and 28 KLG3). Lyon-Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined. RESULTS: At 6 months, qMRI demonstrated a -3.7% "annualised" change in cartilage thickness (SRM -0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was -0.68/-0.13 and at 24 months was -0.62/-0.20. The SRM for cMFTC changes measured with qMRI was -0.32 (12 months; -2.0%) and -0.48 (24 months; -2.2%), respectively. CONCLUSIONS: qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.

Osteoarthritis may not be a one-way-road of cartilage loss--comparison of spatial patterns of cartilage change between osteoarthritic and healthy knees.

OBJECTIVE: To explore whether longitudinal change in cartilage thickness in femorotibial subregions of knees with radiographic osteoarthritis (ROA) differs from that in healthy knees. METHODS: 3T coronal magnetic resonance (MR) images were acquired in 152 women at seven clinical centers at baseline (BL) and 24 months. Knees from 75 women with signs of ROA in either anterior-posterior or Lyon schuss radiographs were compared with those from 77 asymptomatic healthy controls without ROA to identify knees showing greater change in cartilage thickness than expected based on observations in healthy knees. The femorotibial cartilage thickness was determined in BL and follow-up MR images across five tibial and three femoral subregions in the medial/lateral compartment, respectively. RESULTS: A substantial portion of knees with ROA were classified as having longitudinal cartilage thinning (28%) or thickening (20%) in at least one medial femorotibial subregion based on comparisons to longitudinal changes observed in healthy knees; only 5% showed both subregional thinning and thickening across (different) medial subregions at the same time. Whereas the estimated proportion of Kellgren Lawrence grade (KLG) 3 knees (n=28) with significant medial cartilage thinning (46%) was substantially greater than that with cartilage thickening (18%), the estimated percentages of KLG2 knees (n=30) with significant medial thinning (20%) and thickening (23%) were similar. CONCLUSION: This exploratory study indicates that OA may not be a one-way-road of cartilage loss. Subregional analysis suggests that, compared with healthy knees, cartilage changes in ROA may occur in both directions. Medial femorotibial cartilage thickening was observed as frequently as cartilage thinning in KLG2 knees.

The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year.

OBJECTIVES: To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS: Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS: JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION: Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.

Relation of regional articular cartilage morphometry and meniscal position by MRI to joint space width in knee radiographs.

OBJECTIVE: To ascertain the contribution of articular cartilage morphometry and meniscal position on MRI to joint space width (JSW) measured in the Lyon schuss radiograph of the knee. DESIGN: 62 obese women with knee OA and 99 non-obese female controls (mean age 56.6 years) were imaged using 3T MRI and coronal water excitation spoiled gradient echo sequences. Segmentation of femorotibial cartilage morphology and regional morphometric analysis was performed using custom software. Meniscal position was measured quantitatively in sagittal and coronal planes. Minimum space width (mJSW) was measured in the Lyon Schuss knee radiograph; Kellgren and Lawrence grades (KLG) were assigned on standing anteroposterior knee films. The relative contribution of regional cartilage thickness and meniscal position to mJSW was assessed initially in univariate models and subsequently with multivariable modelling. RESULTS: 65% of the variation in mJSW was explained by regional cartilage thickness measures, different KLG and meniscal coverage. Of these measures the medial tibia cartilage thickness measures and central region of the central medial femur (ccMF) play a consistent role in variations in mJSW observed across all KLG. Further ccMF and the addition of percent meniscal coverage to this model explains the remaining differences in mean mJSW found between those subjects with definite joint space narrowing (KLG3) and those without OA. CONCLUSION: The variation in radiographic mJSW is best described by five regional cartilage thickness measures and percent meniscal coverage. The magnitude of each measures contribution differs according to radiographic severity with more variability explained by cartilage thickness of ccMF cartilage thickness and percent meniscal coverage with more severe disease.

Subregional femorotibial cartilage morphology in women--comparison between healthy controls and participants with different grades of radiographic knee osteoarthritis.

OBJECTIVE: To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA). DESIGN: 158 women aged > or =40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)< or =28, no symptoms, and were AP KLG0. 61 women had a BMI> or =30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified. RESULTS: KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered. CONCLUSIONS: The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others.

Solid ion-exchange electrode selective for calcium ion.

A calcium-selective electrode with solid ion exchanger was prepared from a solution of the calcium salt of a dialkylphosphoric acid in collodion. The electrode responds rapidly and reproducibly to activity of calcium ion and demonstrates a selective response for calcium ion in the presence of alkaline earth and alkali metal cations.

Head-to-head comparison of the Lyon Schuss and fixed flexion radiographic techniques. Long-term reproducibility in normal knees and sensitivity to change in osteoarthritic knees.

OBJECTIVE: The Lyon Schuss (LS) and fixed flexion (FF) views of the knee are superior to a conventional standing anteroposterior view in evaluating joint space narrowing (JSN) in osteoarthritis (OA). Both position the knee identically but only the LS aligns the medial tibial plateau (MTP) with the x-ray beam fluoroscopically. The present study provides the first head-to-head comparison of the LS and FF views. METHODS: At baseline and 12 months, 62 OA and 99 control knees were imaged twice on the same day with LS and FF views. Minimum joint space width (mJSW) was measured by computer and MTP alignment was assessed from the distance between anterior and posterior margins of the MTP (intermargin distance, IMD). Reproducibility of measurements of mJSW and sensitivity to change were evaluated. RESULTS: In normal knees, JSW did not vary over 12 months with either view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the LS view and -0.01 (0.46) mm with the FF view (p = 0.0002 and p = 0.92, respectively). Mean IMD was only half as large in LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p<0.0001). CONCLUSIONS: LS and FF radiographs offer similar reproducibility in JSW measurement. However, presumably due to its superiority in aligning the MTP, the LS view is much more sensitive to JSN in OA knees.

Precision of 3.0 Tesla quantitative magnetic resonance imaging of cartilage morphology in a multicentre clinical trial.

OBJECTIVE: Quantitative MRI (qMRI) of cartilage morphology is a promising tool for disease-modifying osteoarthritis drug (DMOAD) development. Recent studies at single sites have indicated that measurements at 3.0 Tesla (T) are more reproducible (precise) than those at 1.5 T. Precision errors and stability in multicentre studies with imaging equipment from various vendors have, however, not yet been evaluated. METHODS: A total of 158 female participants (97 Kellgren and Lawrence grade (KLG) 0, 31 KLG 2 and 30 KLG 3) were imaged at 7 clinical centres using Siemens Magnetom Trio and GE Signa Excite magnets. Double oblique coronal acquisitions were obtained at baseline and at 3 months, using water excitation spoiled gradient echo sequences (1.0x0.31x0.31 mm3 resolution). Segmentation of femorotibial cartilage morphology was performed using proprietary software (Chondrometrics GmbH, Ainring, Germany). RESULTS: The precision error (root mean square coefficient of variation (RMS CV)%) for cartilage thickness/volume measurements ranged from 2.1%/2.4% (medial tibia) to 2.9%/3.3% (lateral weight-bearing femoral condyle) across all participants. No significant differences in precision errors were observed between KLGs, imaging sites, or scanner manufacturers/types. Mean differences between baseline and 3 months ranged from <0.1% (non-significant) in the medial to 0.94% (p<0.01) in the lateral femorotibial compartment, and were 0.33% (p<0.02) for the total femorotibial subchondral bone area. CONCLUSIONS: qMRI performed at 3.0 T provides highly reproducible measurements of cartilage morphology in multicentre clinical trials with equipment from different vendors. The technology thus appears sufficiently robust to be recommended for large-scale multicentre trials.

Ribonucleotides: conditionally essential nutrients shown to enhance immune function and reduce diarrheal disease in infants.

It remains a goal of pediatric nutrition to provide optimal nourishment for infants who are not fed human milk. Investigators have attempted to emulate the composition and functionality of human milk, the gold standard for infant nutrition. These efforts began with the analysis of milk components and continued with assessments of biological effects that culminated in clinical studies in infants. This chapter summarizes the path that researchers followed to study ribonucleotides and their role in infant nutrition. Based on analytical methods for the quantification of ribonucleotides in human milk, investigators assessed their potential impact on the immune systems of infants and looked for concomitant mechanistic explanations. These inquiries evolved into clinical trials in which ribonucleotide-supplemented formula performance was compared with that of non-supplemented formulas and with human milk. This chapter intends to summarize an area of pediatric nutrition that has yielded both enlightening evidence and seemingly contradictory data.

Bioaccessible arsenic in the home environment in southwest England.

Samples of household dust and garden soil were collected from twenty households in the vicinity of an ex-mining site in southwest England and from nine households in a control village. All samples were analysed by ICP-MS for pseudo-total arsenic (As) concentrations and the results show clearly elevated levels, with maximum As concentrations of 486 microg g(-1) in housedusts and 471 microg g(-1) in garden soils (and mean concentrations of 149 microg g(-1) and 262 microg g(-1), respectively). Arsenic concentrations in all samples from the mining area exceeded the UK Soil Guideline Value (SGV) of 20 microg g(-1). No significant correlation was observed between garden soil and housedust As concentrations. Bioaccessible As concentrations were determined in a small subset of samples using the Physiologically Based Extraction Test (PBET). For the stomach phase of the PBET, bioaccessibility percentages of 10-20% were generally recorded. Higher percentages (generally 30-45%) were recorded in the intestine phases with a maximum value (for one of the housedusts) of 59%. Data from the mining area were used, together with default values for soil ingestion rates and infant body weights from the Contaminated Land Exposure Assessment (CLEA) model, to derive estimates of As intake for infants and small children (0-6 years old). Dose estimates of up to 3.53 microg kg(-1) bw day(-1) for housedusts and 2.43 microg kg(-1) bw day(-1) for garden soils were calculated, compared to the index dose used for the derivation of the SGV of 0.3 microg kg(-1) bw day(-1) (based on health risk assessments). The index dose was exceeded by 75% (18 out of 24) of the estimated As doses that were calculated for children aged 0-6 years, a group which is particularly at risk from exposure via soil and dust ingestion. The results of the present study support the concerns expressed by previous authors about the significant As contamination in southwest England and the potential implications for human health.

Comparison of the degree of contact guidance between tumor cells and normal cells in vitro.

A comparison was made between the degree of contact guidance produced by grooved or ridged substrata in cultures of normal mouse embryonic fibroblasts and in fibrosarcoma EMT6 cells or cells of a dibenzanthracene-induced fibrosarcoma. Normal mouse mammary epithelial cells were also compared with cells of C3HBA mammary tumor. All types of cell showed a highly significant orientation in the direction of the grooves or ridges, but there were significantly lower proportions of aligned tumor cells than of their normal counterparts. Fibroblasts showed more alignment than did normal mammary epithelial cells, and the sarcoma cells showed more alignment than did the C3HBA tumor cells. Scanning electron microscopy of cells growing on ridged substrata revealed that all types of cells adhere to the ridges rather than to flat areas between ridges. The difference between normal and malignant cells appears to indicate a real difference in a behavioral characteristic, namely, that tumor cells are less responsive to the topographical features of the substratum that are their normal counterparts. The local infiltration of tissues by tumor cells is due to factors other than contact guidance, for it occurs in spite of their lower contact guidance compared to that of normal cells.