Gait risk factors for disease progression differ between non-traumatic and post-traumatic knee osteoarthritis.

OBJECTIVE: To examine if relationships between knee osteoarthritis (OA) progression with knee moments and muscle activation during gait vary between patients with non-traumatic and post-traumatic knee OA. DESIGN: This longitudinal study included participants with non-traumatic (n = 17) and post-traumatic (n = 18) knee OA; the latter group had a previous anterior cruciate ligament rupture. Motion capture cameras, force plates, and surface electromyography measured knee moments and lower extremity muscle activation during gait. Cartilage volume change were determined over 2 years using magnetic resonance imaging in four regions: medial and lateral plateau and condyle. Linear regression analysis examined relationships between cartilage change with gait metrics (moments, muscle activation), group, and their interaction. RESULTS: Measures from knee adduction and rotation moments were related to lateral condyle cartilage loss in both groups, and knee adduction moment to lateral plateau cartilage loss in the non-traumatic group only [ß = -1.336, 95% confidence intervals (CI) = -2.653 to -0.019]. Generally, lower levels of stance phase muscle activation were related to greater cartilage loss. The relationship between cartilage loss in some regions with muscle activation characteristics varied between non-traumatic and post-traumatic groups including for: lateral hamstring (lateral condyle ß = 0.128, 95%CI = 0.003 to 0.253; medial plateau ß = 0.199, 95%CI = 0.059 to 0.339), rectus femoris (medial condyle ß = -0.267, 95%CI = -0.460 to -0.073), and medial hamstrings (medial plateau; ß = -0.146, 95%CI = -0.244 to -0.048). CONCLUSION: Findings indicate that gait risk factors for OA progression may vary between patients with non-traumatic and post-traumatic knee OA. These OA subtypes should be considered in studies that investigate gait metrics as risk factors for OA progression.

Relationship between alignment and cartilage thickness in patients with non-traumatic and post-traumatic knee osteoarthritis.

OBJECTIVE: To compare cartilage thickness between patients with non-traumatic and post-traumatic knee osteoarthritis (OA) and healthy controls and to determine if disease severity and alignment impact these differences. DESIGN: Participants with non-traumatic (n = 22) and post-traumatic (n = 19) knee OA, and healthy controls (n = 22) were recruited for this cross-sectional study. Participants underwent 3T magnetic resonance imaging (T1-weighted, 3D sagittal gradient echo sequence) and cartilage thickness was determined in four regions: medial and lateral condyle, and medial and lateral plateau. Lower extremity alignment (mechanical axis angle) and disease severity (Kellgren-Lawrence scores) were measured from full length radiographs. Statistical analysis included one-way analysis of variance (ANOVA) and modified Bonferroni test adjusting for multiple pairwise comparisons. Linear regression analyses examined the relationship between cartilage thickness and knee OA group after controlling for disease severity, meniscal status, and alignment. RESULTS: In participants with predominantly medial compartment knee OA, compared to healthy controls, those with non-traumatic knee OA had diminished cartilage thickness in the medial plateau (p = 0.035) and those with post-traumatic knee OA had greater cartilage thickness in the lateral condyle (p = 0.044). In the lateral condyle, data revealed that alignment accounted for the variance in cartilage thickness (p = 0.035), in which a stronger relationship was found in the non-traumatic (r = -0.61) than the post-traumatic (r = -0.12) OA group. CONCLUSIONS: Emerging data demonstrated that participants with non-traumatic knee OA have a stronger relationship between alignment and cartilage thickness than those with post-traumatic knee OA. This indicates that factors involved in knee OA initiation and progression may differ between these OA subtypes.

The ratio adipsin/MCP-1 is strongly associated with structural changes and CRP/MCP-1 with symptoms in obese knee osteoarthritis subjects: data from the Osteoarthritis Initiative.

OBJECTIVE: There is a need to identify reliable biomarkers that can predict knee osteoarthritis (OA) progression. We investigated a panel of adipokines and some related inflammatory factors alone and their ratios for their associative value at assessing cartilage volume loss over time and symptoms in obese [High body mass index (BMI)] and non-obese (Low BMI) OA subjects. DESIGN: Human OA serum was from the Osteoarthritis Initiative Progression subcohort. Baseline levels of adiponectin (high and low molecular weight forms), adipsin, chemerin, leptin, visfatin, C-reactive protein (CRP), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were evaluated with specific assays. Cartilage volume was assessed at baseline and 48 months by quantitative magnetic resonance imaging (MRI), and symptoms using baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Data were analysed by linear regression with confounding factors at baseline, followed by multiple comparison adjustment. RESULTS: The levels of the nine biomarkers and their ratios (36) were studied. Among High BMI subjects, only the ratio adipsin/MCP-1 was associated with cartilage volume loss over time in the lateral compartment [ß, -2.95; 95% confidence interval (CI), -4.42, -1.49; P = 0.010], whereas MCP-1 was associated with WOMAC pain (-1.74; -2.75, -0.73; P = 0.030) and the ratio CRP/MCP-1 with WOMAC pain (0.76; 0.37, 1.14; P = 0.023), function (2.43; 1.20, 3.67; P = 0.020) and total (3.29; 1.58, 5.00; P = 0.027). No associations were found for biomarkers or ratios in Low BMI OA. CONCLUSION: In this study, the ratio adipsin/MCP-1 was found to be associated with the knee structural changes and that of CRP/MCP-1 with symptoms in obese OA subjects. Our data further underline the relevance of ratios as biomarkers to a stronger association to OA progression and symptoms.

Meniscal extrusion and bone marrow lesions are associated with incident and progressive knee osteoarthritis.

OBJECTIVE: Whether meniscal extrusion and bone marrow lesions (BMLs) are independently associated with the risk of knee osteoarthritis (OA) is unknown. METHODS: Data was extracted from the Osteoarthritis Initiative (OAI) cohort. Participants were grouped according to the absence (Kellgren-Lawrence (KL) grade ≤ 1, n = 2120) or presence (KL ≥ 2, n = 2249) of radiographic OA (ROA). Baseline meniscal extrusion and tibial BMLs were assessed. Tibial plateau cartilage volume was assessed at baseline and 72 months, while radiographic disease was assessed at baseline and 48 months. Total knee replacement (TKR) was assessed at 72 months. RESULTS: In those with ROA, the presence of a baseline meniscal extrusion (independent of BMLs) was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.5%; lateral: -2.6%/annum vs -1.6%; both P < 0.001), progressive ROA and TKR (Odds ratio (OR) range 1.4-1.8; 95% CI range 1.1-2.9). The presence of a baseline BML was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.6%; lateral: -1.9%/annum vs -1.6%; P ≤ 0.02), progressive ROA and joint replacement (OR range 1.5-2.4; 95% CI range 1.1-3.4). In those with no ROA, a baseline medial meniscal extrusion was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.2%, P < 0.001), and a baseline medial BML with incident ROA (OR 1.7, 95% CI 1.1 to 2.9). CONCLUSIONS: The presence of baseline meniscal extrusion and BMLs are associated with incident and progressive knee of each other (OA) and represent important structural targets for the treatment and prevention of knee OA.

A pilot randomized controlled trial evaluating outdoor community walking for knee osteoarthritis: walk.

OBJECTIVES: To determine the feasibility of a randomized controlled trial (RCT) examining outdoor walking on knee osteoarthritis (KOA) clinical outcomes and magnetic resonance imaging (MRI) structural changes. METHOD: This was a 24-week parallel two-arm pilot RCT in Tasmania, Australia. KOA participants were randomized to either a walking plus usual care group or a usual care control group. The walking group trained 3 days/week. The primary outcome was feasibility assessed by changes being required to the study design, recruitment, randomization, program adherence, safety, and retention. Exploratory outcomes were changes in symptoms, physical performance/activity, and MRI measures. RESULTS: Forty participants (mean age 66 years (SD 1.4) and 60% female) were randomized to walking (n = 24) or usual care (n = 16). Simple randomization resulted in a difference in numbers randomized to the two groups. During the study, class sizes were reduced from 10 to 8 participants to improve supervision, and exclusion criteria were added to facilitate program adherence. In the walking group, total program adherence was 70.0% and retention 70.8% at 24 weeks. The walking group had a higher number of mild adverse events and experienced clinically important improvements in symptoms (e.g., visual analogue scale (VAS) knee pain change in the walking group: - 38.7 mm [95% CI - 47.1 to - 30.3] versus usual care group: 4.3 mm [- 4.9 to 13.4]). CONCLUSIONS: This study supports the feasibility of a full-scale RCT given acceptable adherence, retention, randomization, and safety, and recruitment challenges have been identified. Large symptomatic benefits support the clinical usefulness of a subsequent trial. TRIAL REGISTRATION NUMBER: 12618001097235. Key Points • This pilot study is the first to investigate the effects of an outdoor walking program on knee osteoarthritis clinical outcomes and MRI joint structure, and it indicates that a full-scale RCT is feasible. • The outdoor walking program (plus usual care) resulted in large improvements in self-reported knee osteoarthritis symptoms compared to usual care alone. • The study identified recruitment challenges, and the manuscript explores these in more details and provides recommendations for future studies.

The associations between parity, other reproductive factors and cartilage in women aged 50-80 years.

OBJECTIVE: Sex hormones and reproductive factors may be important for osteoarthritis (OA). The aim of this study was to describe the associations of parity, use of hormone replacement therapy (HRT) and oral contraceptives (OCs) with cartilage volume, cartilage defects and radiographic OA in a population-based sample of older women. DESIGN: Cross-sectional study of 489 women aged 50-80 years. Parity, use of HRT and OC was assessed by questionnaire; knee cartilage volume and defects by magnetic resonance imaging and knee joint space narrowing (JSN) and osteophytes by X-ray. RESULTS: Parity was associated with a deficit in total knee cartilage volume [adjusted ß=-0.69 ml, 95% confidence interval (CI) -1.34, -0.04]. Increasing parity was associated with decreasing cartilage volume in both the tibial compartment and total knee (both P trend <0.05). Parity was also associated with greater cartilage defects in the patella compartment [adjusted odds ratio (OR)=2.87, 95% CI=1.39, 5.93] but not other sites. There was a consistent but non-significant increase in knee JSN (OR=2.78, 95% CI=0.75, 10.31) and osteophytes (OR=1.69, 95% CI=0.59, 4.82) for parous women. Use of HRT and/or OC was not associated with cartilage volume, cartilage defects or radiographic change. CONCLUSIONS: Parity (but not use of HRT or OC) is independently associated with lower cartilage volume primarily in the tibial compartment and higher cartilage defects in the patella compartment in this population-based sample of older women.

A metaproteomic approach gives functional insights into anaerobic digestion.

AIMS: The objective of this work was to provide functional evidence of key metabolic pathways important for anaerobic digestion processes through the identification of highly expressed proteins in a mixed anaerobic microbial consortium. METHODS AND RESULTS: The microbial communities from an anaerobic industrial-like wastewater treatment bioreactor were characterized using phylogenetic analyses and metaproteomics. Clone libraries indicated that the bacterial community in the bioreactor was diverse while the archaeal population was mainly composed of Methanocorpusculum-like (76%) micro-organisms. Three hundred and eighty-eight reproducible protein spots were obtained on 2-D gels, of which 70 were excised and 33 were identified. The putative functions of the proteins detected in the anaerobic bioreactor were related to cellular processes, including methanogenesis from CO(2) and acetate, glycolysis and the pentose phosphate pathway. Metaproteomics also indicated, by protein assignment, the presence of specific micro-organisms in the bioreactor. However, only a limited overlap was observed between the phylogenetic and metaproteomic analyses. CONCLUSIONS: This study provides some direct evidence of the microbial activities taking place during anaerobic digestion. SIGNIFICANCE AND IMPACT OF STUDY: This study demonstrates metaproteomics as a useful tool to uncover key biochemical pathways underpinning specific anaerobic bioprocesses.

Decrease in serum level of matrix metalloproteinases is predictive of the disease-modifying effect of osteoarthritis drugs assessed by quantitative MRI in patients with knee osteoarthritis.

OBJECTIVES: To explore the impact of disease-modifying osteoarthritis drug (DMOAD) treatment on biomarker levels and their correlation with cartilage volume loss and disease symptoms in a 2-year phase III clinical trial in patients with knee OA. METHODS: 161 patients with knee OA (according-to-protocol population) were selected from a 2-year DMOAD trial studying the effect of licofelone (200 mg twice daily) versus naproxen (500 mg twice daily). Clinical evaluation of patients was carried out using the Western Ontario and McMaster Universities (WOMAC) questionnaire. Biomarker measurements of matrix metalloproteinase (MMP)-1, MMP-3, interleukin (IL)-6, C reactive protein (CRP), cartilage oligomeric matrix protein (COMP) and type I collagen C-terminal telopeptide (CTX-I) in serum, type II collagen C-terminal telopeptide (CTX-II) in urine, and knee MRI were performed at baseline and 2 years. RESULTS: Over time an increase occurred in all biomarker levels with the exception of IL-6, CRP and CTX-II which decreased. The increase in MMP-1 and MMP-3 was significantly less (p = 0.05; p < 0.01, respectively) in the licofelone group. The baseline MMP-1 level was significantly but inversely predictive of cartilage volume loss for the medial compartment in both univariate (p = 0.04) and multivariate (p ≤ 0.04) regression analyses, and COMP, a predictor for the lateral compartment, in both univariate and multivariate models (p < 0.01). Baseline levels of IL-6 and CRP also showed a significant relationship with volume loss for the medial compartment (univariate analysis, p = 0.04 and p = 0.01, respectively; multivariate analysis, p = 0.03, p = 0.01). A significant association (univariate) was observed between the change in the levels of MMP-1 (p = 0.03) and MMP-3 (p = 0.02) and cartilage volume loss (lateral compartment) over 2 years. Baseline levels of CTX-I correlated (p = 0.02) with an increase in the size of the bone marrow lesion in the medial compartment. The baseline CRP levels correlated with worsening of symptoms: WOMAC total index (p < 0.01), pain (p < 0.01) and function (p < 0.01). CONCLUSION: Higher baseline values of IL-6, CRP and COMP are predictive of greater risk of cartilage loss in OA. However, over time a reduction in MMP-1 and MMP-3 levels correlated best with reduction in cartilage volume loss and the effect of drug treatment. Baseline CRP was found to be a good predictor of the symptomatic response to treatment.

Landspreading with co-digested cattle slurry, with or without pasteurisation, as a mitigation strategy against pathogen, nutrient and metal contamination associated with untreated slurry.

North Atlantic European grassland systems have a low nutrient use efficiency and high rainfall. This grassland is typically amended with unprocessed slurry, which counteracts soil organic matter depletion and provides essential plant micronutrients but can be mobilised during rainfall events thereby contributing to pathogen, nutrient and metal incidental losses. Co-digesting slurry with waste from food processing mitigates agriculture-associated environmental impacts but may alter microbial, nutrient and metal profiles and their transmission to watercourses, and/or soil persistence, grass yield and uptake. The impact of EU and alternative pasteurisation regimes on transmission potential of these various pollutants is not clearly understood, particularly in pasture-based agricultural systems. This study utilized simulated rainfall (Amsterdam drip-type) at a high intensity indicative of a worst-case scenario of ~11 mm hr-1 applied to plots 1, 2, 15 and 30 days after grassland application of slurry, unpasteurised digestate, pasteurised digestate (two conditions) and untreated controls. Runoff and soil samples were collected and analysed for a suite of potential pollutants including bacteria, nutrients and metals following rainfall simulation. Grass samples were collected for three months following application to assess yield as well as nutrient and metal uptake. For each environmental parameter tested: microbial, nutrient and metal runoff losses; accumulation in soil and uptake in grass, digestate from anaerobic co-digestion of slurry with food processing waste resulted in lower pollution potential than traditional landspreading of slurry without treatment. Reduced microbial runoff from digestate was the most prominent advantage of digestate application. Pasteurisation of the digestate further augmented those environmental benefits, without impacting grass output. Anaerobic co-digestion of slurry is therefore a multi-beneficial circular approach to reducing impacts of livestock production on the environment.

Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI.

OBJECTIVE: In a multicentre study to explore the effects of licofelone as a disease-modifying osteoarthritis drug in comparison with naproxen in patients with knee osteoarthritis (OA), using MRI and x-ray examination. METHODS: Patients with knee OA (n = 355) were randomised to receive either licofelone (200 mg twice a day) or naproxen (500 mg twice a day). MRI and x-ray examinations were performed at baseline, 6 months (MRI only), 12 and 24 months. MRI was used to assess quantitatively changes in cartilage volume, and x-ray examinations (Lyon-Schuss) to measure changes in the mean and minimum joint space width (JSW) in the medial compartment. Questionnaires probing symptoms were completed. Data were presented as intention to treat (ITT) and according to protocol (ATP). RESULTS: Cartilage volume loss in the global joint and medial and lateral compartments was significantly less in the licofelone than in the naproxen group for ITT at 12 and 24 months and for ATP at all times except in the medial compartment. Patients with medial meniscal extrusion had a greater loss of cartilage volume. In these patients, licofelone markedly reduced the cartilage loss for both ITT and ATP at 12 and 24 months. Although licofelone showed less reduction in the JSW than naproxen, this did not reach significance. All clinical variables were improved at 24 months (p<0.001) for both groups, with a good safety profile. CONCLUSION: Licofelone and naproxen were equally effective in reducing OA symptoms; however, licofelone significantly reduced cartilage volume loss over time, thus having a protective effect in patients with knee OA. This study proves the superiority of quantitative MRI over x-ray examinations in a multicentre clinical trial.

Factors affecting the haptic filled-space illusion for dynamic touch.

In the haptic filled-space illusion for active dynamic touch, observers move their fingertip across an unfilled extent or an extent filled with intermediate stimulations. Previous researchers have reported lengths of filled extents to be overestimated, but the parameters affecting the strength of the illusion are still largely unknown. In the current research, we show that the illusion persists when intermediate stimulations do not provide information about the extent's length. In addition, the results show that the strength of the illusion increases with the number of filler elements. In contrast with earlier research, we control for movement speed differences between filled and unfilled extents. The results suggest that the strength of the illusion is independent of the overall average movement speed. Insight into factors affecting the strength of the illusion may provide a better understanding of the kinematic mechanisms underlying haptic length perception.

Magnetic resonance imaging can accurately assess the long-term progression of knee structural changes in experimental dog osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) structural changes take place over decades in humans. MRI can provide precise and reliable information on the joint structure and changes over time. In this study, we investigated the reliability of quantitative MRI in assessing knee OA structural changes in the experimental anterior cruciate ligament (ACL) dog model of OA. METHODS: OA was surgically induced by transection of the ACL of the right knee in five dogs. High resolution three dimensional MRI using a 1.5 T magnet was performed at baseline, 4, 8 and 26 weeks post surgery. Cartilage volume/thickness, cartilage defects, trochlear osteophyte formation and subchondral bone lesion (hypersignal) were assessed on MRI images. Animals were killed 26 weeks post surgery and macroscopic evaluation was performed. RESULTS: There was a progressive and significant increase over time in the loss of knee cartilage volume, the cartilage defect and subchondral bone hypersignal. The trochlear osteophyte size also progressed over time. The greatest cartilage loss at 26 weeks was found on the tibial plateaus and in the medial compartment. There was a highly significant correlation between total knee cartilage volume loss or defect and subchondral bone hypersignal, and also a good correlation between the macroscopic and the MRI findings. CONCLUSION: This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of the joint structural changes during the development of OA in the ACL dog model. The combination of this OA model with MRI evaluation provides a promising tool for the evaluation of new disease-modifying osteoarthritis drugs (DMOADs).

Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period.

OBJECTIVE: To evaluate in patients with knee osteoarthritis (OA) the size changes in bone oedema and cysts over 24 months, and to contrast these changes with cartilage volume loss using quantitative magnetic resonance imaging. METHODS: 107 patients with knee OA, selected from a large trial evaluating the effect of a bisphosphonate, were analysed by magnetic resonance imaging at baseline and 24 months. Assessments of subchondral bone oedema and cysts, and cartilage volume were done. RESULTS: At baseline, 86 patients showed the presence of at least one type of bone lesion: 71 oedema, 61 cysts and 51 both. At 24 months, although not statistically significant, the oedema total size change increased by 2.09 (SD 15.03) mm, and the cyst by 1.09 (8.13) mm; mean size change for the oedema was +0.38 (2.18) mm and -0.10 (4.36) mm for the cyst. When analysed according to subregions, an increase was found for the cyst size in the trochlea (+0.67 (2.74) mm, p = 0.02) and in the lateral tibial plateau (+0.15 (0.83) mm, p = 0.09), and for the oedema size in the medial tibial plateau (+1.73 (8.11) mm, p = 0.05). At 24 months, significant correlations were seen between the loss of cartilage volume and oedema size change in the medial condyle (-0.40, p = 0.0001) and the medial tibial plateau (-0.23, p = 0.03), and the changes in cyst size in the medial condyle (-0.29, p = 0.01). A multivariate analysis showed that the oedema size change was strongly and independently associated with medial cartilage volume loss (-0.31, p = 0.0004). CONCLUSION: These data demonstrate that bone lesions are prevalent in knee OA. The correlation of the oedema and cyst size increase in the medial compartment over time with a greater loss of cartilage volume in this area underlines the importance of subchondral bone lesions in OA pathophysiology.

Identification of components of the sigma B regulon in Listeria monocytogenes that contribute to acid and salt tolerance.

Sigma B (sigma(B)) is an alternative sigma factor that controls the transcriptional response to stress in Listeria monocytogenes and is also known to play a role in the virulence of this human pathogen. In the present study we investigated the impact of a sigB deletion on the proteome of L. monocytogenes grown in a chemically defined medium both in the presence and in the absence of osmotic stress (0.5 M NaCl). Two new phenotypes associated with the sigB deletion were identified using this medium. (i) Unexpectedly, the strain with the DeltasigB deletion was found to grow faster than the parent strain in the growth medium, but only when 0.5 M NaCl was present. This phenomenon was independent of the carbon source provided in the medium. (ii) The DeltasigB mutant was found to have unusual Gram staining properties compared to the parent, suggesting that sigma(B) contributes to the maintenance of an intact cell wall. A proteomic analysis was performed by two-dimensional gel electrophoresis, using cells growing in the exponential and stationary phases. Overall, 11 proteins were found to be differentially expressed in the wild type and the DeltasigB mutant; 10 of these proteins were expressed at lower levels in the mutant, and 1 was overexpressed in the mutant. All 11 proteins were identified by tandem mass spectrometry, and putative functions were assigned based on homology to proteins from other bacteria. Five proteins had putative functions related to carbon utilization (Lmo0539, Lmo0783, Lmo0913, Lmo1830, and Lmo2696), while three proteins were similar to proteins whose functions are unknown but that are known to be stress inducible (Lmo0796, Lmo2391, and Lmo2748). To gain further insight into the role of sigma(B) in L. monocytogenes, we deleted the genes encoding four of the proteins, lmo0796, lmo0913, lmo2391, and lmo2748. Phenotypic characterization of the mutants revealed that Lmo2748 plays a role in osmotolerance, while Lmo0796, Lmo0913, and Lmo2391 were all implicated in acid stress tolerance to various degrees. Invasion assays performed with Caco-2 cells indicated that none of the four genes was required for mammalian cell invasion. Microscopic analysis suggested that loss of Lmo2748 might contribute to the cell wall defect observed in the DeltasigB mutant. Overall, this study highlighted two new phenotypes associated with the loss of sigma(B). It also demonstrated clear roles for sigma(B) in both osmotic and low-pH stress tolerance and identified specific components of the sigma(B) regulon that contribute to the responses observed.

Proteomic analyses of a Listeria monocytogenes mutant lacking sigmaB identify new components of the sigmaB regulon and highlight a role for sigmaB in the utilization of glycerol.

In Listeria monocytogenes the alternative sigma factor sigmaB plays important roles in both virulence and stress tolerance. In this study a proteomic approach was used to define components of the sigmaB regulon in L. monocytogenes 10403S (serotype 1/2a). Using two-dimensional gel electrophoresis and the recently developed isobaric tags for relative and absolute quantitation technique, the protein expression profiles of the wild type and an isogenic delta sigB deletion strain were compared. Overall, this study identified 38 proteins whose expression was sigmaB dependent; 17 of these proteins were found to require the presence of sigmaB for full expression, while 21 were expressed at a higher level in the delta sigB mutant background. The data obtained with the two proteomic approaches showed limited overlap (four proteins were identified by both methods), a finding that highlights the complementarity of the two technologies. Overall, the proteomic data reaffirmed a role for sigmaB in the general stress response and highlighted a probable role for sigmaB in metabolism, especially in the utilization of alternative carbon sources. Proteomic and physiological data revealed the involvement of sigmaB in glycerol metabolism. Five newly identified members of the sigmaB regulon were shown to be under direct regulation of sigmaB using reverse transcription-PCR (RT-PCR), while random amplification of cDNA ends-PCR was used to map four sigmaB-dependent promoters upstream from lmo0796, lmo1830, lmo2391, and lmo2695. Using RT-PCR analysis of known and newly identified sigmaB-dependent genes, as well as proteomic analyses, sigmaB was shown to play a major role in the stationary phase of growth in complex media.

Temporal assessment of bone marrow lesions on magnetic resonance imaging in a canine model of knee osteoarthritis: impact of sequence selection.

OBJECTIVE: To assess the evolution of bone marrow lesions (BMLs) in a canine model of knee osteoarthritis (OA) using three different magnetic resonance imaging (MRI) sequences. DESIGN: Three MRI sequences [coronal, T1-weighted three-dimensional fast gradient recalled echo (T1-GRE), sagittal fat-suppressed 3D spoiled gradient echo at a steady state (SPGR), and sagittal T2-weighted fast spin echo with fat saturation (T2-FS)] were performed at baseline, and at week 4, 8 and 26 in five dogs following transection of the anterior cruciate ligament. The same reader scored (0-3) subchondral BMLs twice, in blinded conditions, according to their extent in nine joint subregions, for all imaging sessions, and independently on the three MRI sequences. Correlation coefficients and Bland-Altman plots evaluated intra-reader repeatability. Readings scores were averaged and the nine subregions were summed to generate global BML scores. RESULTS: BMLs were most prevalent in the central and medial portions of the tibial plateau. Intra-reader repeatability was good to excellent for each sequence (r(s)=0.87-0.97; P<0.001). Maximal intra-reader variability (24%) was reached on T2-FS and was associated to higher scores (P<0.05). Global BML scores increased similarly on all three sequences until week 8 (P<0.05). At week 26, score on T2-FS was decreased, being lower when compared to T1-GRE and SPGR (P<0.05). CONCLUSION: In this canine OA model, the extent of BMLs varies in time on different MRI sequences. Until the complex nature of these lesions is fully resolved, it is suggested that to accurately assess the size and extent of BMLs, a combination of different sequences should be used.

A new non-invasive method to assess synovitis severity in relation to symptoms and cartilage volume loss in knee osteoarthritis patients using MRI.

OBJECTIVES: Synovitis in knee osteoarthritis (OA) patients is a significant risk factor for disease progression. This study aimed at developing a magnetic resonance imaging (MRI) scoring system allowing reliable and sensitive assessment of synovitis severity in knee OA patients without the use of a contrast agent. METHODS: Imaging was performed without contrast agent, using a 1.5T and a knee coil. For the synovial membrane, the MRI exam included two axial sequences: a T2-weighted (synovial fluid) and a gradient echo (GRE) (synovial membrane). Synovial membrane thickness was measured on four regions of interest (ROI): medial and lateral recesses, and medial and lateral suprapatellar bursa, with each graded/scored from 0 to 3, for a maximum of 12. A validation study was performed on a cohort of 27 knee OA patients having MRI at baseline. A subset of 14 patients had an additional MRI acquisition and symptom assessment at Day 60. Evaluation of disease symptoms was done with Western Ontario and McMaster Universities OA Index and visual analog scale, and of cartilage volume, menisci and subchondral bone, with MR images from a 3D spoiled gradient recalled (SPGR) sequence. RESULTS: The synovial membrane thickness grade was 1.9+/-0.5 (mean+/-SD) with a score of 7.1+/-2.3. The intra-reader (r=0.91) and inter-reader (r=0.82) correlation coefficients were excellent (P<0.0001). The medial compartment grade was 1.9+/-0.6 and score was 3.4+/-1.4, and of the lateral compartment were 2.0+/-0.7 and 3.7+/-1.5, respectively. The grade and score for the suprapatellar bursa and recess were 1.8+/-0.7 and 3.5+/-1.5, and 2.1+/-0.5 and 3.9+/-0.9, respectively. No statistically significant differences in the ROI score and grade were observed between medial and lateral compartments or between recess and suprapatellar bursa. A positive correlation was found between the global severity of synovitis at baseline and the presence of a medial meniscal extrusion (P<0.04), and the loss of cartilage volume at 60 days (P<0.03). CONCLUSION: This newly developed MRI technology for the assessment of synovial membrane thickness in knee OA patients was shown to be accurate and reproducible.

Peer-delivered interventions reduce HIV risk behaviors among out-of-treatment drug abusers.

OBJECTIVE: The purpose of this chapter is to describe the results of a randomized study (funded by the National Institute on Drug Abuse [NIDA]) comparing a peer-delivered enhanced intervention to the NIDA standard intervention for reducing human immunodeficiency virus (HIV) risk behaviors. METHODS: Data come from the ongoing St. Louis Each One Teach One (EOTO) study on HIV risk behaviors among out-of-treatment crack cocaine users and injecting drug users (IDUs). The study has a randomized prospective design, and for this chapter, three risk behaviors were analyzed--the frequency of crack cocaine use and the number of sex partners and condom use over the past 30-day period. We report the level of risk at baseline and at the three-month follow-up period to determine the proportion of individuals improving or worsening based on a dichotomous outcome in which remaining at low risk or decreasing moderate or high risk behaviors is considered "improving" and increasing risk behavior or remaining at moderate or high risk is considered "worsening". RESULTS: Overall, 80% of the sample "improved" their crack cocaine use, meaning they maintained at low level or reduced their use. Although both the standard and enhanced intervention groups made substantial improvement in their crack cocaine use, individuals in the enhanced intervention group were statistically more likely to reduce their risk than those assigned to the standard intervention (83% vs. 75%, P < 0.05). As for the number of sex partners, 75% of the overall sample improved; that is, they reduced the number of sex partners or remained abstinent or in a one-partner relationship at baseline and follow-up. There was no statistically significant difference between the enhanced and standard groups (76% vs 73%). Stratified by gender, the results showed a trend toward improvement among women assigned to the enhanced intervention compared with those assigned to the standard. In terms of condom use, the overall sample worsened more than it improved (65% vs. 44%), and no differences were found between the enhanced and standard groups. CONCLUSIONS: These findings show that the use of peers as role models in promoting HIV risk reduction is feasible and effective among out-of-treatment drug abusers, particularly for drug use itself. Condom use was found to be more difficult to change than other behaviors. Possible reasons for this lack of improvement and suggestions for future interventions are given.

[Stress urinary incontinence in women. Physiopathology and surgical treatment using Burch's technique and TVT]. / Incontinence urinaire d'effort chez la femme. Physiopathologie et traitement chirurgical par les techniques de Burch et TVT.

FROM PHYSIOPATHOLOGY TO TREATMENT: Urinary incontinence on effort in women is due to a default in sub-urethral anatomical structure, which leads to incontinence on effort (coughing, laughing, carrying heavy weights, physical activity). When re-education fails, surgical treatment using Burch's technique or the placing of sub-urethral TVT (Tension free Vaginal Tape) is generally proposed. BURCH'S TECHNIQUE: Burch's technique consists in an upper tract colposuspension via coelioscopy or laparotomy, under rachis or general anaesthesia. In the literature, the following rates of complete cure have been presented: 64 to 87%, 75 to 95% and 63 to 89% respectively in the short, median and long term together with the cure of certain complications (vesicular instability, dysuria, secondary prolapse, infections). THE TVT TECHNIQUE: Developed in the early nineties, the placing of TVT is a mini-invasive technique requiring the use of polypropylene tape inserted vaginally under the urethra under rachis or local anaesthesia. It is associated with over 80% median term clinical efficacy and rare complications (vesicular perforation, arterial wounds, perineal haematoma, dysuria, infections).

[Immediate resection-anastomosis after intra-operative colonic irrigation in cancer of the left colon with obstruction]. / Résection-anastomose immédiate après lavage colique per-opératoire dans le cancer du côlon gauche en occlusion.

In a consecutive series of 38 patients over 5 years, who required emergency surgery for obstructing left colonic carcinoma, 24 had primary bowel resection with immediate anastomosis, after intraoperative anterograde colonic irrigation. Complete colonic obstruction was present in all cases. There were 7 Dukes B tumors, 11 Dukes C tumors and 6 Dukes D tumors. The operative mortality was 8.3% (2 patients, with one from anastomotic leakage), anastomotic leakage rate was 4%. Superficial wound infection occurred in 4% of patients. The median postoperative hospital stay was 19.5 days. The Kaplan-Meier survival curve showed a 41% survival rate after 5 years. This technique was found to be safe and effective to perform a primary anastomosis, without requiring temporary colostomies, after emergency resection of selected left colonic carcinoma obstruction.