Background and Purpose-Walking ability poststroke is commonly assessed using gait speed categories developed by Perry et al. The purpose of this study was to reexamine factors that predict home and community ambulators determined from real-world walking activity data using activity monitors. Methods-Secondary analyses of real-world walking activity from 2 stroke trials. Home (100-2499 steps/d), most limited community (2500-4499 steps/d), least limited community (5000-74 999), and full community (≥7500 steps/d) walking categories were developed based on normative data. Independent variables to predict walking categories were comfortable and fast gait speed, 6-minute walk test, Berg Balance Scale, Fugl Meyer, and Stroke Impact Scale. Data were analyzed using multivariate analyses to identify significant variables associated with walking categories, bootstrap method to select the most stable model and receiver-operating characteristic to identify cutoff values. Results-Data from 441 individuals poststroke were analyzed. The 6-minute walk test, Fugl Meyer, and Berg Balance Scale combined were the strongest predictors of home versus community and limited versus unlimited community ambulators. The 6-minute walk test was the strongest individual variable in predicting home versus community (receiver-operating characteristic area under curve=0.82) and limited versus full community ambulators (receiver-operating characteristic area under curve=0.76). A comfortable gait speed of 0.49 m/s discriminated between home and community and a comfortable gait speed of 0.93 m/s discriminated between limited community and full community ambulators. Conclusions-The 6-minute walk test was better able to discriminate among home, limited community, and full community ambulators than comfortable gait speed. Gait speed values commonly used to distinguish between home and community walkers may overestimate walking activity.

Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.

A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetra chloride (CCL4)-treated rats. The assay was further evaluated in a clinical study of prostate-, lung- and breast-cancer patients stratified according to skeletal metastases. A technically robust ELISA assay specific for a MMP-2, -9 and -13 neo-epitope was produced and seen to be statistically elevated in BDL rats compared to baseline levels as well as significantly elevated in CCL4 rats stratified according to the amount of total collagen in the livers. CO1-764 levels also correlated significantly with total liver collagen and type I collagen mRNA expression in the livers. Finally, the CO1-764 marker was not correlated with skeletal involvement or number of bone metastases. This ELISA has the potential to assess the degree of liver fibrosis in a non-invasive manner.

BackgroundThe emergence of hookah is being noted on college campuses and in large U.S. cities and evidence points to an increasing trend for college students. The purpose of this study was to assess hookah use and identify associations with cigarette smoking and demographic factors.MethodsAn intercept sampling method was used at various locations on a large university campus in the southeastern United States, yielding a high participation rate (52%). A total of 1,203 participants completed a computer-aided survey that assessed the use of tobacco products. The sample characteristics were then weighted to match the University population of students enrolled during the same semester. Bivariate (chi-square and t-test) and multivariate (logistic regression) tests of association were conducted to assess differences between cigarette and hookah users.ResultsHookah smoking exceeded cigarette smoking for both ever use (46.4% vs 42.1%) and past year use (28.4% vs 19.6%). Females and males used hookah at similar rates. Hispanic respondents had the highest prevalence of current use of hookah (18.9%) and cigarettes (16.4%).ConclusionsAs hookah surpasses cigarette use, efforts need to be made to slow the increase in new tobacco products that are attractive to young adults and that pose many of the same health risks as those related to traditional tobacco products. Prevalence of all emerging tobacco products, including hookah, and the relationship with cigarette use needs to be monitored on an ongoing basis.

This newly developed serum assay specific for P4NP 7S was highly related to liver fibrosis and correlated to extent of hepatic fibrosis. This assay may improve fibrosis quantification.

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Background and purpose: Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB 2 )-selective aminoalkylindole with antinociceptive efficacy in animal pain models. The purpose of our studies was to provide a characterization of R,S-AM1241 and its resolved enantiomers in vitro and in vivo. Experimental approach: Competition binding assays were performed using membranes from cell lines expressing recombinant human, rat, and mouse CB 2 receptors. Inhibition of cAMP was assayed using intact CB 2 -expressing cells. A mouse model of visceral pain (para-phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were employed to characterize the compounds in vivo. Key results: In cAMP inhibition assays, R,S-AM1241 was found to be an agonist at human CB 2 , but an inverse agonist at rat and mouse CB 2 receptors. R-AM1241 bound with more than 40-fold higher affinity than S-AM1241, to all three CB 2 receptors and displayed a functional profile similar to that of the racemate. In contrast, S-AM1241 was an agonist at all three CB 2 receptors. In pain models, S-AM1241 was more efficacious than either R-AM1241 or the racemate. Antagonist blockade demonstrated that the in vivo effects of S-AM1241 were mediated by CB 2 receptors. Conclusions and implications: These findings constitute the first in vitro functional assessment of R,S-AM1241 at rodent CB 2 receptors and the first characterization of the AM1241 enantiomers in recombinant cell systems and in vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB 2 agonist enantiomer of AM1241, is consistent with previous observations that CB 2 agonists are effective in relief of pain.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by excessive inflammatory and immune responses and tissue damage. Increasing evidence has demonstrated the important role of programmed cell death in SLE pathogenesis. When apoptosis encounters with defective clearance, accumulated apoptotic cells lead to secondary necrosis. Different forms of lytic cell death, including secondary necrosis after apoptosis, NETosis, necroptosis, and pyroptosis, contribute to the release of damage-associated molecular patterns (DAMPs) and autoantigens, resulting in triggering immunity and tissue damage in SLE. However, the role of autophagy in SLE pathogenesis is in dispute. This review briefly discusses different forms of programmed cell death pathways and lay particular emphasis on inflammatory cell death pathways such as NETosis, pyroptosis, and necroptosis and their roles in the inflammatory and immune responses in SLE.