Inclusion body myositis in the rheumatology clinic

Inclusion body myositis is a rare sporadic inflammatory‐degenerative myopathy of the elderly. Despite being the commonest type of acquired myopathy after the age of 50, misdiagnosis is extremely common. The most frequent hurdle in identifying new cases is the wrong diagnosis of polymyositis or motor neuron disease. Novel insights into pathogenic mechanisms have heralded the quest for newer therapeutics as well as drug repurposing in this otherwise progressive disorder.     

A national interactive web-based physical activity intervention in women, evaluation of the american heart association choose to move program 2006-2007

Increased physical activity (PA) is associated with improvement of cardiac risk factors and prevention of cardiovascular disease, yet many women remain sedentary. With rising Internet use, Web-based interventions provide an alternative to improve PA, but their effectiveness for change in PA and quality of life (QOL) in a real-world setting is unknown. Participants were United States women ≥18 years old who received 12 weekly PA modules and completed surveys on PA, QOL, and readiness for PA at registration (registration cohort, n = 3,796) or registration and 12 weeks (evaluation cohort, n = 892). QOL was assessed with a modified Short Form-36 with subscores for energy and well-being. Participants showed significant (p <0.001) favorable changes in PA (baseline, median 240 kcal/week, interquartile range 62 to 667; 12 weeks, 343 kcal/week, 131 to 828), stage of readiness for PA, and body mass index (baseline, 29.3 kg/m(2), 24.9 to 34.7; 12 weeks, 28.9 kg/m(2), 24.6 to 34.2). Significant improvements (p <0.0001) were also found in composite scores for energy and well-being. Compliance with PA guideline recommendations increased from 15.8% to 21.4%. Program weeks completed (p = 0.03), energy (p = 0.04), and well-being (p = 0.002) were significantly associated with achieving guideline compliance. In women reporting no PA at baseline (n = 88), program participation resulted in 54.6% achieving some PA and another 9.1% achieving total compliance with recommendations. In conclusion, in this national cohort of women, a 12-week Web-based intervention improved PA and QOL measurements, resulting in higher short-term PA guideline compliance and better QOL. Increasing use of this simple Web-based tool could improve PA and promote disease prevention.     

Inflammaging: disturbed interplay between autophagy and inflammasomes

Inflammaging refers to a low-grade pro-inflammatory phenotype which accompanies aging in mammals. The aging process is associated with a decline in autophagic capacity which impairs cellular housekeeping, leading to protein aggregation and accumulation of dysfunctional mitochondria which provoke reactive oxygen species (ROS) production and oxidative stress. Recent studies have clearly indicated that the ROS production induced by damaged mitochondria can stimulate intracellular danger-sensing multiprotein platforms called inflammasomes. Nod-like receptor 3 (NLRP3) can be activated by many danger signals, e.g. ROS, cathepsin B released from destabilized lysosomes and aggregated proteins, all of which evoke cellular stress and are involved in the aging process. NLRP3 activation is also enhanced in many age-related diseases, e.g. atherosclerosis, obesity and type 2 diabetes. NLRP3 activates inflammatory caspases, mostly caspase-1, which cleave the inactive precursors of IL-1β and IL-18 and stimulate their secretion. Consequently, these cytokines provoke inflammatory responses and accelerate the aging process by inhibiting autophagy. In conclusion, inhibition of autophagic capacity with aging generates the inflammaging condition via the activation of inflammasomes, in particular NLRP3. We will provide here a perspective on the current research of the ROS-dependent activation of inflammasomes triggered by the decline in autophagic cleansing of dysfunctional mitochondria.     

Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response

Recent studies have shown that a single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene plays a major role in predicting therapeutic response in hepatitis C virus (HCV)-infected patients treated with pegylated interferon (PEG-IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics, IFN pharmacokinetics, IFN pharmacodynamics, and gene expression profiles. Two prospective cohorts (human immunodeficiency virus [HIV]/HCV-coinfected and HCV-monoinfected) completing treatment with IFN/ribavirin were enrolled. Patients were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort, frequent serum sampling was completed for HCV RNA and IFN levels. DNA microarray of peripheral blood mononuclear cells and individual expression of IFN-stimulated genes (ISGs) were quantified on IFN therapy. The IL28B-favorable (CC) genotype was associated with improved therapeutic response compared with unfavorable (CT or TT) genotypes. Patients with a favorable genotype had greater first- and second-phase viral kinetics (P = 0.004 and P = 0.036, respectively), IFN maximum antiviral efficiency (P = 0.007) and infected cell death loss (P = 0.009) compared with unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of natural killer cells, from patients with unfavorable genotypes (P <0.004). Induction of innate immunity genes was also lower in unfavorable genotypes. ISG expression at baseline and induction with IFN was independent of IL28B genotype. CONCLUSION: Carriers of the IL28B-favorable genotype were more likely to have superior innate immune response to IFN therapy compared with unfavorable genotypes, suggesting that the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated with more rapid viral kinetics and improved treatment response outcomes independent of ISG expression.     

Comparative efficacy of the Picture Exchange Communication System (PECS) versus a speech-generating device: Effects on requesting skills

An experimental, single-subject research study investigated the comparative efficacy of the Picture Exchange Communication System (PECS) versus a speech-generating device (SGD) in developing requesting skills for three elementary-age children with severe autism and little to no functional speech. Results demonstrated increases in requesting behavior for all participants across intervention phases with both augmentative and alternative communication (AAC) intervention strategies; however, difficulties were observed with picture discrimination. The Wilcoxon signed pair test did not reveal significant differences between PECS and the SGD for any participant. Findings suggest PECS and SGD are equally appropriate for developing initial requesting skills. Based on the current findings, successful implementation of either AAC strategy is achievable when appropriate instructional strategies are used.     

Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor‐of‐risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross‐sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L₄ in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual‐energy X‐ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = –[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load‐to‐strength ratio helps explain increased fracture risk in both low‐weight and obese women. © 2015 American Society for Bone and Mineral Research.