Running Biomechanics and Knee Cartilage Health in ACLR Patients

Anterior cruciate ligament reconstruction (ACLR) patients are more likely to subsequently suffer from knee osteoarthritis than non-ACLR counterparts. Exercise is thought to influence articular cartilage, however, it is unclear how running biomechanics are associated with femoral cartilage thickness and composition in ACLR patients. PURPOSE: The purpose of this study was to investigate relationships between running biomechanics and measures of femoral articular cartilage condition (thickness and composition) in ACLR patients and control subjects. METHODS: We used ultrasound and MRI (T2 mapping sequence) to measure articular cartilage thickness and composition, respectively, for 20 ACLR patients (age: 23 ± 3 yrs; mass: 70 ± 10 kg; time post-ACLR: 14.6 ± 6.1 months) and 20 matched controls (age: 22 ± 2 yrs; mass: 67 ± 11 kg). After these measures, all participants completed a 30-minute run on a force-instrumented treadmill. Correlational analyses were used to explore relationships between running biomechanics (vertical ground reaction force (vGRF)) and femoral cartilage thickness and composition (T2 relaxation time). The present procedures were approved by the appropriate institutional board and all subjects provided informed consent before data collection was performed. RESULTS: Significant positive correlations existed for the control subjects only between peak vGRF and overall (r = 0.34; p \u3c 0.01), medial (r = 0.23; p \u3c 0.01), lateral (r = 0.39; p = 0.02), and intercondylar (r = 0.31; p \u3c 0.01) femoral thickness. The ACLR patients showed significant negative correlations between T2 relaxation time for the central-medial region of the femoral condyle, and peak vGRF (r = −0.53; p = 0.01) and vertical impulse due to the vGRF (r = −0.46; p = 0.04). CONCLUSION: These findings offer some limited support for the idea that femoral articular cartilage benefits from increase vGRF during running. This is evidenced by the increased thickness for the control subjects and decreased T2 relaxation time (indicative of increased free-flowing water in the cartilage) for the ACLR patients, as running vGRF increased

Effects of Running on Femoral Articular Cartilage Thickness for Anterior Cruciate Ligament Reconstruction Patients and Non-ACLR Control Subjects

Anterior cruciate ligament reconstruction (ACLR) patients are more likely to develop posttraumatic knee osteoarthritis than non-ACLR counterparts. The effect of running on femoral articular cartilage thickness is unclear. PURPOSE: The purpose of this study was to compare how 30 minutes of running influences femoral articular cartilage thickness for ACLR patients and non-ACLR control subjects. We hypothesized that running would deform the femoral articular cartilage more for the ACLR patients than for the control subjects. METHODS: We recruited 20 individuals with primary unilateral ACLR and 20 matched non-ACLR controls. ACLR patients and control subjects were matched based upon age, gender, BMI, and weekly running mileage. The present procedures were approved by the appropriate institutional board and all subjects provided informed consent before data collection. We used ultrasound imaging to measure femoral articular cartilage thickness before and after 30 minutes of running. The ultrasound images were manually analyzed using ImageJ software by the same investigator. Total femoral articular cartilage cross-sectional area of each image was segmented into three regions: medial, lateral, and intercondylar. Deformation due to the run was compared between the ACLR patients and control subjects for each region using independent t tests (P \u3c 0.05, adjusted for multiple comparisons). RESULTS: The 30-minute run resulted in more deformation for the ACLR patients (0.03 ± 0.01 cm) than the matched controls (0.01 ± 0.01 cm) for the medial region (p \u3c 0.01) of the femoral articular cartilage. Identically, the 30-minute run resulted in more deformation for the ACLR patients (0.03 ± 0.01 cm) than the matched controls (0.01 ± 0.01 cm; p \u3c 0.01) for an average of the entire articular cartilage area (medial, lateral, and intercondylar). No significant differences existed between groups for the lateral or intercondylar regions. CONCLUSION: Thirty minutes of running deformed medial and overall femoral articular cartilage more for ACLR patients than non-ACLR control subjects

Femoral Articular Cartilage Quality, but Not Thickness, Is Decreased for Anterior Cruciate Ligament Reconstruction Patients Relative to Control

Anterior cruciate ligament reconstruction (ACLR) patients are at risk of developing posttraumatic knee osteoarthritis (OA). The etiology of posttraumatic knee OA is complex, potentially involving biomechanical and biochemical factors. Changes in femoral cartilage thickness and composition are associated with knee OA, while current research is ambiguous on cartilage in ACLR patients. PURPOSE: This study aimed to compare femoral cartilage thickness and T2 relaxation time (a compositional measure) between ACLR patients and healthy controls in a resting state. We hypothesized that ACLR patients would exhibit thinner femoral cartilage and increased T2 relaxation times. METHODS: Twenty ACLR patients (6-24 months post-surgery) and 20 matched healthy controls were recruited following institutional board approval. Ultrasound and magnetic resonance imaging data were collected on two separate days, allowing cartilage thickness and composition measurements to be made, respectively. Statistical analyses, including independent t-tests and Holm-Bonferroni corrections, were performed on selected regions of interest. RESULTS: The ACLR group showed increased T2 relaxation times in four of eight femoral regions compared to controls. No significant differences in femoral cartilage thickness were observed between the groups. The primary finding from this study is that ACLR patients did not show differences in femoral cartilage thickness (a morphological measure), but displayed prolonged T2 relaxation times (a compositional measure) compared to controls, at rest. This finding suggests that compositional changes precede morphological shifts in femoral cartilage in early post-ACLR periods (6-24 months). CONCLUSION: These early compositional changes may indicate articular cartilage that is more compressible and subject to increased strain on the solid components of the joint. While ultrasound is a more accessible imaging method, magnetic resonance imaging may provide a more accurate and early evaluation of cartilage quality. Further research is needed to develop practical tools for early detection and monitoring of cartilage degradation in ACLR patients before progression into knee osteoarthritis

LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation

Background: Infection with adeno-associated virus (AAV) vector with liver tropism leads to persistent expression of foreign antigens in the mouse liver, with no significant liver inflammation or pathology. This provides a model to investigate antigen persistence in the liver and strategies to modulate host immunity to reduce or clear the foreign antigen expressed from AAV vector in the liver. Methods/Principal Findings: We showed that expressing LIGHT with an adenovirus vector (Ad) in mice with established AAV in the liver led to clearance of the AAV. Ad-LIGHT enhanced CD8 effector T cells in the liver, correlated with liver inflammation. LTbR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTbR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. Conclusions/Significance: Our data suggest that LIGHT interaction with the LTbR plays a critical role in liver inflammation but is not required for LIGHT-mediated AAV clearance. These findings will shed light on developing novel immunotherapeutic

A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4+ T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4+ T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

Natural Killer Cell Signal Integration Balances Synapse Symmetry and Migration

Imaging immune surveillance by natural killer (NK) cells has revealed that integration of activating and inhibitory signals determines whether or not NK cells stop to kill the target cell or retain a migratory configuration

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version