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.     

Improved Detection of Rare HIV-1 Variants using 454 Pyrosequencing

454 pyrosequencing, a massively parallel sequencing (MPS) technology, is often used to study HIV genetic variation. However, the substantial mismatch error rate of the PCR required to prepare HIV-containing samples for pyrosequencing has limited the detection of rare variants within viral populations to those present above ~1%. To improve detection of rare variants, we varied PCR enzymes and conditions to identify those that combined high sensitivity with a low error rate. Substitution errors were found to vary up to 3-fold between the different enzymes tested. The sensitivity of each enzyme, which impacts the number of templates amplified for pyrosequencing, was shown to vary, although not consistently across genes and different samples. We also describe an amplicon-based method to improve the consistency of read coverage over stretches of the HIV-1 genome. Twenty-two primers were designed to amplify 11 overlapping amplicons in the HIV-1 clade B gag-pol and env gp120 coding regions to encompass 4.7 kb of the viral genome per sample at sensitivities as low as 0.01-0.2%.     

Scale Effects between Body Size and Limb Design in Quadrupedal Mammals

Recently the metabolic cost of swinging the limbs has been found to be much greater than previously thought, raising the possibility that limb rotational inertia influences the energetics of locomotion. Larger mammals have a lower mass-specific cost of transport than smaller mammals. The scaling of the mass-specific cost of transport is partly explained by decreasing stride frequency with increasing body size; however, it is unknown if limb rotational inertia also influences the mass-specific cost of transport. Limb length and inertial properties – limb mass, center of mass (COM) position, moment of inertia, radius of gyration, and natural frequency – were measured in 44 species of terrestrial mammals, spanning eight taxonomic orders. Limb length increases disproportionately with body mass via positive allometry (length ∝ body mass^0.40); the positive allometry of limb length may help explain the scaling of the metabolic cost of transport. When scaled against body mass, forelimb inertial properties, apart from mass, scale with positive allometry. Fore- and hindlimb mass scale according to geometric similarity (limb mass ∝ body mass^1.0), as do the remaining hindlimb inertial properties. The positive allometry of limb length is largely the result of absolute differences in limb inertial properties between mammalian subgroups. Though likely detrimental to locomotor costs in large mammals, scale effects in limb inertial properties appear to be concomitant with scale effects in sensorimotor control and locomotor ability in terrestrial mammals. Across mammals, the forelimb''s potential for angular acceleration scales according to geometric similarity, whereas the hindlimb''s potential for angular acceleration scales with positive allometry.     

Targeted Lipidomics in Drosophila melanogaster Identifies Novel 2-Monoacylglycerols and N-acyl Amides

Lipid metabolism is critical to coordinate organ development and physiology in response to tissue-autonomous signals and environmental cues. Changes to the availability and signaling of lipid mediators can limit competitiveness, adaptation to environmental stressors, and augment pathological processes. Two classes of lipids, the N-acyl amides and the 2-acyl glycerols, have emerged as important signaling molecules in a wide range of species with important signaling properties, though most of what is known about their cellular functions is from mammalian models. Therefore, expanding available knowledge on the repertoire of these lipids in invertebrates will provide additional avenues of research aimed at elucidating biosynthetic, metabolic, and signaling properties of these molecules. Drosophila melanogaster is a commonly used organism to study intercellular communication, including the functions of bioactive lipids. However, limited information is available on the molecular identity of lipids with putative biological activities in Drosophila. Here, we used a targeted lipidomics approach to identify putative signaling lipids in third instar Drosophila larvae, possessing particularly large lipid mass in their fat body. We identified 2-linoleoyl glycerol, 2-oleoyl glycerol, and 45 N-acyl amides in larval tissues, and validated our findings by the comparative analysis of Oregon-RS, Canton-S and w1118 strains. Data here suggest that Drosophila represent another model system to use for the study of 2-acyl glycerol and N-acyl amide signaling.