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Evanston, IL, United States

Chang A.,Northwestern University | Moisio K.,Northwestern University | Chmiel J.S.,Northwestern University | Eckstein F.,Paracelsus Medical University | And 7 more authors.
Annals of the Rheumatic Diseases

Objectives: Meniscal tears have been linked to knee osteoarthritis progression, presumably by impaired load attenuation. How meniscal tears affect osteoarthritis is unclear; subregional examination may help to elucidate whether the impact is local. This study examined the association between a tear within a specifi c meniscal segment and subsequent 2-year cartilage loss in subregions that the torn segment overlies. Methods: Participants with knee osteoarthritis underwent bilateral knee MRI at baseline and 2 years. Mean cartilage thickness within each subregion was quantifi ed. Logistic regression with generalised estimating equations were used to analyse the relationship between baseline meniscal tear in each segment and baseline to 2-year cartilage loss in each subregion, adjusting for age, gender, body mass index, tear in the other two segments and extrusion. Results: 261 knees were studied in 159 individuals. Medial meniscal body tear was associated with cartilage loss in external subregions and in central and anterior tibial subregions, and posterior horn tear specifi cally with posterior tibial subregion loss; these relationships were independent of tears in the other segments and persisted in tibial subregions after adjustment for extrusion. Lateral meniscal body and posterior horn tear were also associated with cartilage loss in underlying subregions but not after adjustment for extrusion. Cartilage loss in the internal subregions, not covered by the menisci, was not associated with meniscal tear in any segment. Conclusion: These results suggest that the detrimental effect of meniscal tears is not spatially uniform across the tibial and femoral cartilage surfaces and that some of the effect is experienced locally. Source

Moisio K.,Northwestern University | Chang A.,Northwestern University | Eckstein F.,Paracelsus Medical University | Eckstein F.,Chondrometrics GmbH | And 8 more authors.
Arthritis and Rheumatism

Objective: Varus-valgus alignment has been linked to subsequent progression of osteoarthritis (OA) within the mechanically stressed (medial for varus, lateral for valgus) tibiofemoral compartment. Cartilage data from the off-loaded compartment are sparse. The purpose of this study was to examine our hypotheses that neutral and valgus (versus varus) knees each have reduced odds of cartilage loss in the medial subregions and that neutral and varus (versus valgus) knees each have reduced odds of cartilage loss in the lateral subregions. Methods: Patients with knee OA underwent knee magnetic resonance imaging at baseline and 2 years. The mean cartilage thickness was quantified within 5 tibial and 3 femoral subregions. We used logistic regression with generalized estimating equations to analyze the relationship between baseline alignment and subregional cartilage loss at 2 years, adjusting for age, sex, body mass index, and disease severity. Results: A reduced risk of cartilage loss in the medial subregions was associated with neutral (versus varus) alignment (external tibial, central femoral, external femoral) and with valgus (versus varus) alignment (central tibial, external tibial, central femoral, external femoral). A reduced risk of cartilage loss in the lateral subregions was associated with neutral (versus valgus) alignment (central tibial, internal tibial, posterior tibial) and with varus (versus valgus) alignment (central tibial, external tibial, posterior tibial, external femoral). Conclusion: Neutral and valgus alignment were each associated with a reduction in the risk of subsequent cartilage loss in certain medial subregions and neutral and varus alignment with a reduction in the risk of cartilage loss in certain lateral subregions. These results support load redistribution as an in vivo mechanism of the long-term alignment effects on cartilage loss in knee OA. © 2011, American College of Rheumatology. Source

Visalli M.A.,Mercer University | House B.L.,Mercer University | Lahrman F.J.,Indiana University - Purdue University Fort Wayne | Lahrman F.J.,North Shore University Health Systems | Visalli R.J.,Mercer University
Journal of Virology

The herpesviral terminase complex is part of the intricate machinery that delivers a single viral genome into empty preformed capsids (encapsidation). The varicella-zoster virus (VZV) terminase components (pORF25, pORF30, and pORF45/42) have not been studied as extensively as those of herpes simplex virus 1 and human cytomegalovirus (HCMV). In this study, VZV bacterial artificial chromosomes (BACs) were generated with small (Δ30S), medium (Δ30M), and large (Δ30L) ORF30 internal deletions. In addition, we isolated recombinant viruses with specific alanine substitutions in the putative zinc finger motif (30-ZF3A) or in a conserved region (region IX) with predicted structural similarity to the human topoisomerase I core subdomains I and II (30-IXAla, 30-620A, and 30-622A). Recombinant viruses replicated in an ORF30-complementing cell line (ARPE30) but failed to replicate in noncomplementing ARPE19 and MeWo cells. Transmission electron microscopy of 30-IXAla-, 30-620A-, and 30-622Ainfected ARPE19 cells revealed only empty VZV capsids. Southern analysis showed that cells infected with parental VZV (VZVLUC) or a repaired virus (30R) contained DNA termini, whereas cells infected with Δ30L, 30-IXAla, 30-620A, or 30-622A contained little or no processed viral DNA. These results demonstrated that pORF30, specifically amino acids 619 to 624 (region IX), was required for DNA encapsidation. A luciferase-based assay was employed to assess potential intermolecular complementation between the zinc finger domain and conserved region IX. Complementation between 30-ZF3A and 30-IXAla provided evidence that distinct pORF30 domains can function independently. The results suggest that pORF30 may exist as a multimer or participate in higher-order assemblies during viral DNA encapsidation. © 2015, American Society for Microbiology. Source

Radosevic A.J.,Northwestern University | Mutyal N.N.,Northwestern University | Eshein A.,Northwestern University | Nguyen T.-Q.,Northwestern University | And 10 more authors.
Clinical Cancer Research

Purpose: Colorectal cancer remains the second leading cause of cancer deaths in the United States despite being eminently preventable by colonoscopy via removal of premalignant adenomas. In order to more effectively reduce colorectal cancer mortality, improved screening paradigms are needed. Our group pioneered the use of low-coherence enhanced backscattering (LEBS) spectroscopy to detect the presence of adenomas throughout the colon via optical interrogation of the rectal mucosa. In a previous ex vivo biopsy study of 219 patients, LEBS demonstrated excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The objective of the current cross-sectional study is to assess the viability of rectal LEBS in vivo. Experimental Design: Measurements from 619 patients were taken using a minimally invasive 3.4-mm diameter LEBS probe introduced into the rectum via anoscope or direct insertion, requiring approximately 1 minute from probe insertion to withdrawal. The diagnostic LEBS marker was formed as a logistic regression of the optical reduced scattering coefficient μs ∗ and mass density distribution factor D. Results: The rectal LEBS marker was significantly altered in patients harboring advanced adenomas and multiple nonadvanced adenomas throughout the colon. Blinded and cross-validated test performance characteristics showed 88% sensitivity to advanced adenomas, 71% sensitivity to multiple non-advanced adenomas, and 72% specificity in the validation set. Conclusions: We demonstrate the viability of in vivo LEBS measurement of histologically normal rectal mucosa to predict the presence of clinically relevant adenomas throughout the colon. The current work represents the next step in the development of rectal LEBS as a tool for colorectal cancer risk stratification. © 2015 American Association for Cancer Research. © 2015 American Association for Cancer Research. Source

Portman M.A.,University of Washington | Slee A.,Axio Research | Olson A.K.,University of Washington | Cohen G.,University of Washington | And 7 more authors.

Background-: Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome. Methods and results-: The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7-22) for placebo and 20 hours (CI, 16-45) for Triostat and (hazard ratio, 0.60; P=0.0220). Conclusions-: T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. © 2010 American Heart Association, Inc. Source

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