Future directions for the management of pain in osteoarthritis.

Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future

Fast Benchtop Fabrication of Laminar Flow Chambers for Advanced Microscopy Techniques

Background: Fluid handling technology is acquiring an ever more prominent place in laboratory science whether it is in simple buffer exchange systems, perfusion chambers, or advanced microfluidic devices. Many of these applications remain the providence of laboratories at large institutions with a great deal of expertise and specialized equipment. Even with the expansion of these techniques, limitations remain that frequently prevent the coupling of controlled fluid flow with other technologies, such as coupling microfluidics and high-resolution position and force measurements by optical trapping microscopy. Method: Here we present a method for fabrication of multiple-input laminar flow devices that are optically clear [glass] on each face, chemically inert, reusable, inexpensive, and can be fabricated on the benchtop in approximately one hour. Further these devices are designed to allow flow regulation by a simple gravity method thus requiring no specialized equipment to drive flow. Here we use these devices to perform total internal reflection fluorescence microscopy measurements as well as position sensitive optical trapping experiments. Significance: Flow chamber technology needs to be more accessible to the general scientific community. The method presented here is versatile and robust. These devices use standard slides and coverslips making them compatible with nearly all types and models of light microscopes. These devices meet the needs of groups doing advanced optical trapping experiments, but could also be adapted by nearly any lab that has a function for solution flow coupled with microscopy

Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study

BACKGROUND: The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. METHODS: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. RESULTS AND DISCUSSION: In multivariate analysis, women who were overweight (BMI > 25 to ≤ 30 kg/m(2)) had a 2-fold increase, and obese women (BMI > 30 kg/m(2)) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI ≤25 kg/m(2)) women. When the models for the different measures of adiposity were assessed by multiple R(2), models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. CONCLUSION: Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin

Augmentation of osteochondral repair with hyperbaric oxygenation: a rabbit study

<p>Abstract</p> <p>Background</p> <p>Current treatments for osteochondral injuries often result in suboptimal healing. We hypothesized that the combination of hyperbaric oxygen (HBO) and fibrin would be superior to either method alone in treating full-thickness osteochondral defects.</p> <p>Methods</p> <p>Osteochondral repair was evaluated in 4 treatment groups (control, fibrin, HBO, and HBO+fibrin groups) at 2-12 weeks after surgical injury. Forty adult male New Zealand white rabbits underwent arthrotomy and osteochondral surgery on both knees. Two osteochondral defects were created in each femoral condyle, one in a weight-bearing area and the other in a non-weight-bearing area. An exogenous fibrin clot was placed in each defect in the right knee. Left knee defects were left empty. Half of the rabbits then underwent hyperbaric oxygen therapy. The defects in the 4 treatment groups were then examined histologically at 2, 4, 6, 8, and 12 weeks after surgery.</p> <p>Results</p> <p>The HBO+fibrin group showed more rapid and more uniform repair than the control and fibrin only groups, but was not significantly different from the group receiving HBO alone. In the 2 HBO groups, organized repair and good integration with adjacent cartilage were seen at 8 weeks; complete regeneration was observed at 12 weeks.</p> <p>Conclusions</p> <p>HBO significantly accelerated the repair of osteochondral defects in this rabbit model; however, the addition of fibrin produced no further improvement.</p

Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee

Background and purpose Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

In vitro selectivity, in vivo biodistribution and tumour uptake of annexin V radiolabelled with a positron emitting radioisotope

The availability of a noninvasive method to detect and quantify apoptosis in tumours will enable tumour response to several cancer therapies to be assessed. We have synthesised two radiotracers, annexin V and the N-succinimidyl-3-iodobenzoic acid (SIB) derivative of annexin V, labelled with radio-iodine (124I and 125I) and provided proof of the concept by assessing specific binding and biodistribution of these probes to apoptotic cells and tumours. We have also assessed the tumour uptake of [124I]annexin V in a mouse model of apoptosis. RIF-1 cells induced to undergo apoptosis in vitro showed a drug concentration-dependent increased binding of [125I]annexin V and [125I]SIB–annexin V. In the same model system, there was an increase in terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL)-positive cells and a decrease in clonogenic survival. Radiotracer binding was completely inhibited by preincubation with unlabelled annexin V. In RIF-1 tumour-bearing mice, rapid distribution of [125I]SIB–annexin V-derived radioactivity to kidneys was observed and the radiotracer accumulated in urine. The binding of [125I]SIB–annexin V to RIF-1 tumours increased by 2.3-fold at 48 h after a single intraperitoneal injection of 5-fluorouracil (165 mg kg−1 body weight), compared to a 4.4-fold increase in TUNEL-positive cells measured by immunostaining. Positron emission tomography images with both radiotracers demonstrated intense localisation in the kidneys and bladder. Unlike [124I]SIB–annexin V, [124I]annexin V also showed localisation in the thyroid region presumably due to deiodination of the radiolabel. [124I]SIB–annexin V is an attractive candidate for in vivo imaging of apoptosis by PET

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO