Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Clinical Heterogeneity of Duchenne Muscular Dystrophy (DMD): Definition of Sub-Phenotypes and Predictive Criteria by Long-Term Follow-Up

International audienceBACKGROUND: To explore clinical heterogeneity of Duchenne muscular dystrophy (DMD), viewed as a major obstacle to the interpretation of therapeutic trials METHODOLOGY/PRINCIPAL FINDINGS: A retrospective single institution long-term follow-up study was carried out in DMD patients with both complete lack of muscle dystrophin and genotyping. An exploratory series (series 1) was used to assess phenotypic heterogeneity and to identify early criteria predicting future outcome; it included 75 consecutive steroid-free patients, longitudinally evaluated for motor, respiratory, cardiac and cognitive functions (median follow-up: 10.5 yrs). A validation series (series 2) was used to test robustness of the selected predictive criteria; it included 34 more routinely evaluated patients (age>12 yrs). Multivariate analysis of series 1 classified 70/75 patients into 4 clusters with distinctive intellectual and motor outcomes: A (early infantile DMD, 20%): severe intellectual and motor outcomes; B (classical DMD, 28%): intermediate intellectual and poor motor outcome; C (moderate pure motor DMD, 22%): normal intelligence and delayed motor impairment; and D (severe pure motor DMD, 30%): normal intelligence and poor motor outcome. Group A patients had the most severe respiratory and cardiac involvement. Frequency of mutations upstream to exon 30 increased from group A to D, but genotype/phenotype correlations were restricted to cognition (IQ>71: OR 7.7, 95%CI 1.6-20.4, p6 at 8 yrs" with "normal or borderline mental status" reliably assigned patients to group C (sensitivity: 1, specificity: 0.94). These criteria were also predictive of "early infantile DMD" and "moderate pure motor DMD" in series 2. CONCLUSIONS/SIGNIFICANCE: DMD can be divided into 4 sub-phenotypes differing by severity of muscle and brain dysfunction. Simple early criteria can be used to include patients with similar outcomes in future therapeutic trials

Aconitase B Is Required for Optimal Growth of Xanthomonas campestris pv. vesicatoria in Pepper Plants

The aerobic plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) colonizes the intercellular spaces of pepper and tomato. One enzyme that might contribute to the successful proliferation of Xcv in the host is the iron-sulfur protein aconitase, which catalyzes the conversion of citrate to isocitrate in the tricarboxylic acid (TCA) cycle and might also sense reactive oxygen species (ROS) and changes in cellular iron levels. Xcv contains three putative aconitases, two of which, acnA and acnB, are encoded by a single chromosomal locus. The focus of this study is aconitase B (AcnB). acnB is co-transcribed with two genes, XCV1925 and XCV1926, encoding putative nucleic acid-binding proteins. In vitro growth of acnB mutants was like wild type, whereas in planta growth and symptom formation in pepper plants were impaired. While acnA, XCV1925 or XCV1926 mutants showed a wild-type phenotype with respect to bacterial growth and in planta symptom formation, proliferation of the acnB mutant in susceptible pepper plants was significantly impaired. Furthermore, the deletion of acnB led to reduced HR induction in resistant pepper plants and an increased susceptibility to the superoxide-generating compound menadione. As AcnB complemented the growth deficiency of an Escherichia coli aconitase mutant, it is likely to be an active aconitase. We therefore propose that optimal growth and survival of Xcv in pepper plants depends on AcnB, which might be required for the utilization of citrate as carbon source and could also help protect the bacterium against oxidative stress

Individuals with chronic low back pain have greater difficulty in engaging in positive lifestyle behaviours than those without back pain: An assessment of health literacy

Background: Despite the large volume of research dedicated to understanding chronic low back pain (CLBP), patient outcomes remain modest while healthcare costs continue to rise, creating a major public health burden. Health literacy - the ability to seek, understand and utilise health information - has been identified as an important factor in the course of other chronic conditions and may be important in the aetiology of CLBP. Many of the currently available health literacy measurement tools are limited since they measure narrow aspects of health literacy. The Health Literacy Measurement Scale (HeLMS) was developed recently to measure broader elements of health literacy. The aim of this study was to measure broad elements of health literacy among individuals with CLBP and without LBP using the HeLMS.Methods: Thirty-six community-dwelling adults with CLBP and 44 with no history of LBP responded to the HeLMS. Individuals were recruited as part of a larger community-based spinal health study in Western Australia. Scores for the eight domains of the HeLMS as well as individual item responses were compared between the groups.Results: HeLMS scores were similar between individuals with and without CLBP for seven of the eight health literacy domains (p &gt; 0.05). However, compared to individuals with no history of LBP, those with CLBP had a significantly lower score in the domain &lsquo;Patient attitudes towards their health&rsquo; (mean difference [95% CI]: 0.46 [0.11- 0.82]) and significantly lower scores for each of the individual items within this domain (p &lt; 0.05). Moderate effect sizes ranged from d = 0.47-0.65.Conclusions: Although no differences were identified in HeLMS scores between the groups for seven of the health literacy domains, adults with CLBP reported greater difficulty in engaging in general positive health behaviours. This aspect of health literacy suggests that self-management support initiatives may benefit individuals with CLBP.<br /

Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multisystemic autosomal recessive disease due to primary thymidine phosphorylase (TP) deficiency. To restore TP activity, we performed reduced intensity allogeneic stem cell transplantations (alloSCTs) in two patients. In the first, alloSCT failed to engraft, but the second achieved mixed donor chimerism, which partially restored buffy coat TP activity and lowered plasma nucleosides. Thus, alloSCT can correct biochemical abnormalities in the blood of patients with MNGIE, but clinical efficacy remains unproven