A gait index may underestimate changes of gait: a comparison of the Movement Deviation Profile and the Gait Deviation Index

The ability of the Movement Deviation Profile (MDP) and Gait Deviation Index (GDI) to detect gait changes was compared in a child with cerebral palsy who underwent game training. Conventional gait analysis showed that sagittal plane angles became mirrored about normality after training. Despite considerable gait changes, the GDI showed minimal change, while the MDP detected a difference equal to a shift between 10-9 on the Functional Assessment Questionnaire scale. Responses of the GDI and MDP were examined during a synthetic transition of the patient's curves from before intervention to a state mirrored about normality. The GDI showed a symmetric response on the two opposite sides of normality but the neural network based MDP gave an asymmetric response reflecting faithfully the unequal biomechanical consequences of joint angle changes. In conclusion, the MDP can detect altered gait even if the changes are missed by the GDI.     

Poor knowledge of methotrexate associated with older age and limited English-language proficiency in a diverse rheumatoid arthritis cohort

Introduction

Our objective was to determine rheumatoid arthritis (RA) patients’ understanding of methotrexate and assess whether knowledge varies by age, education, English language proficiency, or other disease-related factors.

Methods

Adults with RA (n = 135) who were enrollees of an observational cohort completed a structured telephone interview in their preferred language between August 2007 and July 2009. All subjects who reported taking methotrexate were asked 11 questions about the medication in addition to demographics, education level, and language proficiency. Primary outcome was a total score below the 50^th percentile (considered inadequate methotrexate knowledge). Bivariable and multivariable logistic regressions were performed. Covariates included demographics, language proficiency, education, and disease characteristics.

Results

Of 135 subjects, 83% were female, with a mean age of 55 ± 14 years. The majority spoke English (64%), followed by 22% Spanish and 14% Cantonese or Mandarin. Limited English language proficiency (LEP) was reported in 42%. Mean methotrexate knowledge score was 5.4 ± 2.6 (range, 0 to 10); 73 (54%) had a score lower than 5 (of 10). Age older than 55, less than high school education, LEP, better function, and biologic use were independently associated with poor knowledge.

Conclusions

In a diverse RA cohort, overall methotrexate knowledge was poor. Older age and limited proficiency in English were significant correlates of poor knowledge. Identification of language barriers and improved clinician-patient communication around methotrexate dosing and side effects may lead to improved safety and enhanced benefits of this commonly used RA medication.     

Chronic vitamin E deficiency promotes vitamin C deficiency in zebrafish leading to degenerative myopathy and impaired swimming behavior

We hypothesized that zebrafish (Danio rerio) undergoing long-term vitamin E deficiency with marginal vitamin C status would develop myopathy resulting in impaired swimming. Zebrafish were fed for 1 y a defined diet without (E ?) and with (E +) vitamin E (500 mg α-tocopherol/kg diet). For the last 150 days, dietary ascorbic acid concentrations were decreased from 3500 to 50 mg/kg diet and the fish sampled periodically to assess ascorbic acid concentrations. The ascorbic acid depletion curves were faster in the E ? compared with E + fish (P < 0.0001); the estimated half-life of depletion in the E ? fish was 34 days, while in it was 55 days in the E + fish. To assess swimming behavior, zebrafish were monitored individually following a “startle-response” stimulus, using computer and video technology. Muscle histopathology was assessed using hematoxylin and eosin staining on paramedian sections of fixed zebrafish. At study end, E ? fish contained 300-fold less α-tocopherol (p < 0.0001), half the ascorbic acid (p = 0.0001) and 3-fold more malondialdehyde (p = 0.0005) than did E + fish. During the first minute following a tap stimulus (p < 0.05), E + fish swam twice as far as did E ? fish. In the E ? fish, the sluggish behavior was associated with a multifocal, polyphasic, degenerative myopathy of the skeletal muscle. The myopathy severity ranged from scattered acute necrosis to widespread fibrosis and was accompanied by increased anti-hydroxynonenal staining. Thus, vitamin E deficiency in zebrafish causes increased oxidative stress and a secondary depletion of ascorbic acid, resulting in severe damage to muscle tissue and impaired muscle function.     

Grassland area determines beetle assemblage dissimilarity from surrounding floodplain forest

Patch size is known to affect biodiversity in fragmented landscapes, but is usually examined in systems where the surrounding matrix habitat is unfavourable. We examined beetle diversity in a floodplain ecosystem that is characterised by naturally occurring grassland patches within a dominant matrix of contrasting yet habitable forest. We asked whether differences in the beetle assemblage between grassland and forest vegetation depended on the area of the grassland patch, which is a function of its flooding frequency and duration: smaller grasslands tend to be higher on the floodplain and are flooded less often and for shorter periods than larger grasslands. We found a negative relationship between grassland area and beetle abundance and species richness, and a positive relationship between grassland area and compositional dissimilarity from the surrounding forest. As expected, we found an overall difference in composition between forest and grassland assemblages, with five beetle species more common in the grasslands. Our study indicates that floodplain grasslands not only support beetle assemblages that are distinct from the surrounding forest, but that assemblages from the larger grasslands are compositionally more distinct than those from smaller grasslands. A likely cause of this pattern is the reduced edge effects and greater environmental contrast between forest and large grasslands that may be exposed to greater variation in local climate. Ongoing changes to flood regimes and potential encroachment of forest plants may decrease grassland area in the future, which may reduce spatial heterogeneity in the insect community in this unique floodplain ecosystem.     

The spatial scaling of beta diversity

Beta diversity is an important concept used to describe turnover in species composition across a wide range of spatial and temporal scales, and it underpins much of conservation theory and practice. Although substantial progress has been made in the mathematical and terminological treatment of different measures of beta diversity, there has been little conceptual synthesis of potential scale dependence of beta diversity with increasing spatial grain and geographic extent of sampling. Here, we evaluate different conceptual approaches to the spatial scaling of beta diversity, interpreted from ‘fixed’ and ‘varying’ perspectives of spatial grain and extent. We argue that a ‘sliding window’ perspective, in which spatial grain and extent covary, is an informative way to conceptualize community differentiation across scales. This concept more realistically reflects the varying empirical approaches that researchers adopt in field sampling and the varying scales of landscape perception by different organisms. Scale dependence in beta diversity has broad implications for emerging fields in ecology and biogeography, such as the integration of fine‐resolution ecogenomic data with large‐scale macroecological studies, as well as for guiding appropriate management responses to threats to biodiversity operating at different spatial scales.     

An Inducible,Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells.