A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Viral (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

Hand joints without radiographic osteoarthritis maintain their joint space width over 4 years despite what's happening elsewhere in the hand.

Objectives: We aimed to determine whether hand OA is characterized by systemic cartilage loss by assessing if radiographically normal joints had greater joint space width (JSW) loss over 4 years in hands with incident or prevalent OA elsewhere in the hand compared with hands without OA.

Methods: We used semi-automated software to measure JSW in the distal and proximal IP joints of 3368 participants in the Osteoarthritis Initiative who had baseline and 48-month hand radiographs. A reader scored 16 hand joints (including the thumb base) for Kellgren-Lawrence (KL) grade.

Increased Joint Space Narrowing After Arthroscopic Partial Meniscectomy: Data From the Osteoarthritis Initiative.

Background: Arthroscopic partial meniscectomy (APM) is widely performed and remains an important therapeutic option for patients with a meniscal tear. However, it is debated whether or not APM accelerates the progression of osteoarthritis (OA) in the long term.

Purpose/hypothesis: The purpose was to compare the progression of OA measured by the change in tibiofemoral joint space width (JSW)-a quantitative measure of OA radiographic severity-across 3 groups with a midterm follow-up: (1) patients undergoing APM; (2) those with a meniscal tear treated nonoperatively; and (3) those without a tear.

Prevalence, Incidence, and Progression of Radiographic and Symptomatic Hand Osteoarthritis: The Osteoarthritis Initiative.

Objective: To describe the prevalence, incidence, and progression of radiographic and symptomatic hand osteoarthritis (OA), and to evaluate differences according to age, sex, race, and other risk factors.

Methods: Participants were assessed for radiographic and symptomatic hand OA at baseline and year 4 to determine incident disease. A modified Poisson regression with a robust variance estimator was used to account for clustering of joints within fingers within persons to estimate the prevalence ratios and relative risk estimates associated with participant characteristics.

Aminopyridine analogs selectively target metastatic pancreatic cancer.

Metastatic outgrowth is supported by metabolic adaptations that may differ from the primary tumor of origin. However, it is unknown if such adaptations are therapeutically actionable. Here we report a novel aminopyridine compound that targets a unique Phosphogluconate Dehydrogenase (PGD)-dependent metabolic adaptation in distant metastases from pancreatic cancer patients.

Differences in the Lateral Compartment Joint Space Width After Anterior Cruciate Ligament Reconstruction: Data From the MOON Onsite Cohort.

Background: Anterior cruciate ligament (ACL) reconstruction can effectively return athletes to the playing field, but they are still at risk of developing posttraumatic osteoarthritis (PTOA). No studies have used multivariable analysis to evaluate the predictors of radiographic PTOA in the lateral compartment of the knee at short-term follow-up after ACL reconstruction.

Purpose: To determine the predictors of radiographic joint space narrowing in the lateral compartment 2 to 3 years after ACL reconstruction in a young, active cohort.

Impact of Cane Use on Bone Marrow Lesion Volume in People With Medial Knee Osteoarthritis (CUBA Trial).

Background: No effective cure exists for knee osteoarthritis (OA). Low-burden self-management strategies that can slow disease progression are needed. Bone marrow lesions (BMLs) are a source of knee pain and accelerate cartilage loss.

Comparison of radiographic joint space width and magnetic resonance imaging for prediction of knee replacement: A longitudinal case-control study from the Osteoarthritis Initiative.

Objective: To evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement.

Methods: Knees replaced between 36 and 60 months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI.

Longitudinal (one-year) change in cartilage thickness in knees with early knee osteoarthritis: A within-person between-knee comparison.

Objective: To test the hypothesis that cartilage displays significant longitudinal thickening in the external subregions of the central medial (ecMF) and lateral (ecLF) femur in knees with early radiographic osteoarthritis (ROA) compared with contralateral knees without ROA, and to explore differences in change in other subregions and in radiographic joint space width (JSW). Methods: 50 participants (50% women; age 61.1±9.

Imaging of osteoarthritis.

Osteoarthritis (OA) is the most prevalent joint disorder in the elderly, and there is no effective treatment. Imaging is essential for evaluating the synovial joint structures (including cartilage, meniscus, subchondral bone marrow and synovium) for diagnosis, prognosis, and follow-up. This article describes the roles and limitations of both conventional radiography and magnetic resonance (MR) imaging, and considers the use of other modalities (eg, ultrasonography, nuclear medicine, computed tomography [CT], and CT/MR arthrography) in clinical practice and OA research.

Cartilage thickening in early radiographic knee osteoarthritis: a within-person, between-knee comparison.

Objective: To determine whether the presence of definite osteophytes (in the absence of joint space narrowing [JSN]) on radiographs is associated with (subregional) increases in cartilage thickness in a within-person, between-knee cross-sectional comparison of participants in the Osteoarthritis Initiative. Based on previous results, the external weight-bearing medial femoral condyle (ecMF) and external weight-bearing lateral femoral condyle (ecLF) subregions were selected as primary end points.

Methods: Both knees of 61 Osteoarthritis Initiative participants (n = 4,796) displayed definite tibial or femoral marginal osteophytes and no JSN in 1 knee, and no signs of radiographic osteoarthritis (OA) in the contralateral knee; this was confirmed by an expert central reader.

Radiographic grading and measurement of joint space width in osteoarthritis.

The progression of osteoarthritis is traditionally measured using radiographic joint space width (JSW). Numerous knee radiograph protocols have been developed with various levels of complexity and performance as it relates to detecting JSW loss (ie, joint space narrowing). Sensitivity to joint space narrowing is improved when radioanatomic alignment of the medial tibial plateau is achieved.

Multiple computer-based methods of measuring joint space width can discriminate between treatment arms in the COBRA trial -- Update of an ongoing OMERACT project.

Previously reported data on 5 computer-based programs for measurement of joint space width focusing on discriminating ability and reproducibility are updated, showing new data. Four of 5 different programs for measuring joint space width were more discriminating than observer scoring for change in narrowing in the 12 months interval. Three of 4 programs were more discriminating than observer scoring for the 0-18 month interval.

Radiographic-based grading methods and radiographic measurement of joint space width in osteoarthritis.

Accurate and highly reproducible measurements of the rate of progression of osteoarthritis is crucial to assessing structural change, and requires adherence to exacting standards of positioning, which include specifications for flexion and rotation of the joint, and angulation of the x-ray beam. The progression of osteoarthritis traditionally has been measured using radiographic joint space width (JSW). Over the past two decades, numerous knee radiographic protocols have been developed with various levels of complexity and performance as they relate to detecting JSW loss (ie, joint space narrowing).

Automated measurement of joint space width in small joints of patients with rheumatoid arthritis.

Objective: Comparison of performances of 5 (semi)automated methods in measuring joint space width (JSW) in rheumatoid arthritis.

Methods: Change in JSW was determined by 5 measurement methods on 4 radiographs per patient from 107 patients included in the COBRA trial (comparing sulfasalazine alone or in combination with methotrexate and corticosteroids). For each method the number of patients with sufficient available results was assessed (efficiency).

Longitudinal performance evaluation and validation of fixed-flexion radiography of the knee for detection of joint space loss.

Objective: The ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed-flexion radiography protocol to detect knee joint space loss over 3 years.

Methods: We assessed the same-day test-retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23-47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA.

Computer based methods for measurement of joint space width: update of an ongoing OMERACT project.

Computer-based methods of measuring joint space width (JSW) could potentially have advantages over scoring joint space narrowing, with regard to increased standardization, sensitivity, and reproducibility. In an early exercise, 4 different methods showed good agreement on measured change in JSW over time in the small joints of the hands and feet. Despite differences in measurement values between methods, measurement of within-joint change over time showed no systematic differences.

Measurement of joint space width and erosion size.

Measurement of radiographic abnormalities in metric units has been reported by several investigators during the last 15 years. Measurement of joint space in large joints has been employed in a few trials to evaluate therapy in osteoarthritis. Measurement of joint space width in small joints has been reported by several investigators but has not yet found a place in clinical trials in rheumatoid arthritis or osteoarthritis.