Update in inclusion body myositis.

The purpose of this study is to review recent scientific advances relating to the natural history, cause, treatment and serum and imaging biomarkers of inclusion body myositis (IBM)

Do clinical and psychosocial factors affect health-related quality of life in adolescents with chronic diseases?

Copyright © 2006 - 2018 The Canadian Center of Science and Education. All Rights Reserved. Copyright for this article is retained by the author(s), with first publication rights granted to the journal. This is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).Living with a chronic disease in adolescence can have an impact on the perception of Health-related Quality of Life (HRQoL). Facing the increasing relevance of psychosocial dimensions and also considering the interaction with clinical variables, this study aimed to measure the impact of clinical and psychosocial factors (separated and combined) on adolescent’s reported HRQoL. A cross-sectional study was conducted in a clinical population of 135 adolescents with chronic diseases (n=70 boys), average age: 14±1.5 years old. Through a self-reported questionnaire, HRQoL (KIDSCREEN-10), socio-demographic, clinical variables (diagnostic; time of diagnosis; self-perceived pain; disease severity proxy; disease-related medication intake/use of special equipment), and psychosocial variables (psychosomatic health; resilience; self-regulation; social support) were assessed. Separately, clinical and psychosocial variables showed a significant impact in HRQoL, 27.9% and 62.4%, respectively. Once combined, the previously identified variables had a significant impact (64.2%), but a different contribution from clinical and psychosocial variables was revealed: when first entering the clinical variables (model 1) the variance only reaches 30%, and much more from psychosocial variables seems to explain the total (64.2%); inversely, when first integrating psychosocial variables (model 2), the clinical ones added a small significance to the model (0.6%). The present study underlined the association of clinical (“disease-related”) and psychosocial (“non-disease-related”) factors on HRQoL. Furthermore, it reinforced the need to focus more on psychosocial dimensions, highlighted the potential role of psychosomatic health, resilience, self-regulation and social support. It can be suggested that the identification of impaired psychosocial domains may help professionals to better plan, and achieve effective interventions of psychosocial care.Santos, T. was supported by a PhD grant from the Portuguese Foundation for Science and Technology (FCT) (Grant Number: reference SFRH/BD/82066/2011). The William James Center for Research, ISPA - Instituto Universitário is supported by a grant from the Portuguese Foundation for Science and Technology (FCT) (Grant Number: UID/PSI/04810/2013). The present study is grateful to all youngsters and parents who participated in this project, also to the health care professionals who collaborated, as well as to the Pediatrics Department of Hospital Santa Maria, CAML (Lisbon Academic Medical Center) for their assistance in this investigation. The authors are also grateful to Prof. Paula Ravasco, MD, PhD (University Hospital of Santa Maria, Portugal) for her assistance in proof-reading and revising the document.info:eu-repo/semantics/publishedVersio

MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study

BACKGROUND: A substantial impediment to progress in trials of new therapies in neuromuscular disorders is the absence of responsive outcome measures that correlate with patient functional deficits and are sensitive to early disease processes. Irrespective of the primary molecular defect, neuromuscular disorder pathological processes include disturbance of intramuscular water distribution followed by intramuscular fat accumulation, both quantifiable by MRI. In pathologically distinct neuromuscular disorders, we aimed to determine the comparative responsiveness of MRI outcome measures over 1 year, the validity of MRI outcome measures by cross-sectional correlation against functionally relevant clinical measures, and the sensitivity of specific MRI indices to early muscle water changes before intramuscular fat accumulation beyond the healthy control range. METHODS: We did a prospective observational cohort study of patients with either Charcot-Marie-Tooth disease 1A or inclusion body myositis who were attending the inherited neuropathy or muscle clinics at the Medical Research Council (MRC) Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK. Genetic confirmation of the chromosome 17p11·2 duplication was required for Charcot-Marie-Tooth disease 1A, and classification as pathologically or clinically definite by MRC criteria was required for inclusion body myositis. Exclusion criteria were concomitant diseases and safety-related MRI contraindications. Healthy age-matched and sex-matched controls were also recruited. Assessments were done at baseline and 1 year. The MRI outcomes-fat fraction, transverse relaxation time (T2), and magnetisation transfer ratio (MTR)-were analysed during the 12-month follow-up, by measuring correlation with functionally relevant clinical measures, and for T2 and MTR, sensitivity in muscles with fat fraction less than the 95th percentile of the control group. FINDINGS: Between Jan 19, 2010, and July 7, 2011, we recruited 20 patients with Charcot-Marie-Tooth disease 1A, 20 patients with inclusion body myositis, and 29 healthy controls (allocated to one or both of the 20-participant matched-control subgroups). Whole muscle fat fraction increased significantly during the 12-month follow-up at calf level (mean absolute change 1·2%, 95% CI 0·5-1·9, p=0·002) but not thigh level (0·2%, -0·2 to 0·6, p=0·38) in patients with Charcot-Marie-Tooth disease 1A, and at calf level (2·6%, 1·3-4·0, p=0·002) and thigh level (3·3%, 1·8-4·9, p=0·0007) in patients with inclusion body myositis. Fat fraction correlated with the lower limb components of the inclusion body myositis functional rating score (ρ=-0·64, p=0·002) and the Charcot-Marie-Tooth examination score (ρ=0·63, p=0·003). Longitudinal T2 and MTR changed consistently with fat fraction but more variably. In muscles with a fat fraction lower than the control group 95th percentile, T2 was increased in patients compared with controls (regression coefficients: inclusion body myositis thigh 4·0 ms [SE 0·5], calf 3·5 ms [0·6]; Charcot-Marie-Tooth 1A thigh 1·0 ms [0·3], calf 2·0 ms [0·3]) and MTR reduced compared with controls (inclusion body myositis thigh -1·5 percentage units [pu; 0·2], calf -1·1 pu [0·2]; Charcot-Marie-Tooth 1A thigh -0·3 pu [0·1], calf -0·7 pu [0·1]). INTERPRETATION: MRI outcome measures can monitor intramuscular fat accumulation with high responsiveness, show validity by correlation with conventional functional measures, and detect muscle water changes preceding marked intramuscular fat accumulation. Confirmation of our results in further cohorts with these and other muscle-wasting disorders would suggest that MRI biomarkers might prove valuable in experimental trials. FUNDING: Medical Research Council UK

A cross-sectional study of memory and executive functions in patients with sporadic inclusion body myositis

INTRODUCTION: Sporadic inclusion body myositis (IBM) is a degenerative and inflammatory acquired myopathy characterised by muscle deposition of various proteins typically associated with Alzheimer's disease and other neurodegenerative diseases. While cognitive impairment is not noted as a clinical feature of IBM, evidence is lacking. We aimed to investigate whether cognitive performance of patients with IBM differs from population norms, focussing on cognitive domains affected in early Alzheimer's disease (memory, executive function), and to test whether disease duration and the level of disability of IBM are associated with cognitive function. METHODS: Twenty-four patients with IBM (mean [SD] age 62.0 [7.2] years; disease duration 9.6 [4.8] years) were assessed cross-sectionally on neuropsychological tests covering multiple cognitive domains, including the Preclinical Alzheimer Cognitive Composite (PACC). Performance was compared to published normative data adjusted for age, sex and education (National Alzheimer's Coordinating Center; N = 3268). Associations were examined between PACC score, disease duration and level of disability (assessed using the IBM Functional Rating Scale [IBMFRS]). RESULTS: Across all cognitive tests, group performance was within ±1SD of the normative mean. There was no evidence of associations between PACC score and either disease duration (ρ = -0.04, p = 0.87) or IBMFRS total score (ρ = 0.14, p = 0.52). DISCUSSION: Memory and executive function in patients with IBM did not differ from normative data, and we observed no evidence of associations between the cognitive composite and disease duration or level of disability. This addresses a question frequently asked by patients, and will be of value for clinicians and patients alike. This article is protected by copyright. All rights reserved

Sporadic inclusion body myositis: the genetic contributions to the pathogenesis

Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease in people over 50 years old. It is characterized by slowly progressive muscle weakness and atrophy, with typical pathological changes of inflammation, degeneration and mitochondrial abnormality in affected muscle fibres. The cause(s) of sIBM are still unknown, but are considered complex, with the contribution of multiple factors such as environmental triggers, ageing and genetic susceptibility. This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology. An international sIBM genetic study is ongoing and whole-exome sequencing will be applied in a large cohort of sIBM patients with the aim of unravelling important genetic risk factors for sIBM

Longitudinal observational study investigating outcome measures for clinical trials in inclusion body myositis.

OBJECTIVE: To describe decline in muscle strength and physical function in patients with sporadic inclusion body myositis (IBM). METHODS: Manual muscle testing (MMT), quantitative muscle testing (QMT) and disability scoring using the IBM Functional Rating Scale (IBMFRS) were undertaken for 181 patients for up to 7.3 years. The relationship between MMT, QMT and IBMFRS composite scores and time from onset were examined using linear mixed effects models adjusted for gender and age of disease onset. Adaptive LASSO regression analysis was used to identify muscle groups that best predicted the time elapsed from onset. Cox proportional hazards regression was used to evaluate time to use of a mobility aid. RESULTS: Multilevel modelling of change in percentage MMT, QMT and IBMFRS score over time yielded an average decline of 3.7% (95% CI 3.1% to 4.3%), 3.8% (95% CI 2.7% to 4.9%) and 6.3% (95% CI 5.5% to 7.2%) per year, respectively. The decline, however, was not linear, with steeper decline in the initial years. Older age of onset was associated with a more rapid IBMFRS decline (p=0.007), but did not influence the rate of MMT/QMT decline. Combination of selected muscle groups allowed for generation of single measures of patient progress (MMT and QMT factors). Median (IQR) time to using a mobility aid was 5.4 (3.6-9.2) years, significantly affected by greater age of onset (HR 1.06, 95% CI 1.04 to 1.09, p<0.001). CONCLUSION: This prospective observational study represents the largest IBM cohort to date. Measures of patient progress evaluated in this study accurately predict disease progression in a reliable and useful way to be used in trial design

Quantification and viability analyses of Pseudokirchneriella subcapitata algal cells using image-based cytometry

This work aims to evaluate the feasibility of using image-based cytometry (IBC) in the analysis of algal cell quantification and viability, using Pseudokirchneriella subcapitata as a cell model. Cell concentration was determined by IBC to be in a linear range between 1×105 and 8×106 cells mL1. Algal viability was defined on the basis that the intact membrane of viable cells excludes the SYTOX Green (SG) probe. The disruption of membrane integrity represents irreversible damage and consequently results in cell death. Using IBC, we were able to successfully discriminate between live (SG-negative cells) and dead algal cells (heat-treated at 65 °C for 60 min; SG-positive cells). The observed viability of algal populations containing different proportions of killed cells was well correlated (R 2=0.994) with the theoretical viability. The validation of the use of this technology was carried out by exposing algal cells of P. subcapitata to a copper stress test for 96 h. IBC allowed us to follow the evolution of cell concentration and the viability of copper-exposed algal populations. This technology overcomes several main drawbacks usually associated with microscopy counting, such as labour-intensive experiments, tedious work and lack of the representativeness of the cell counting. In conclusion, IBC allowed a fast and automated determination of the total number of algal cells and allowed us to analyse viability. This technology can provide a useful tool for a wide variety of fields that utilise microalgae, such as the aquatic toxicology and biotechnology fields.FCT Strategic Project PEst- OE/EQB/LA0023/2013. The post-doctoral grant from FCT (SFRH/BPD/72816/2010)

Arachnidism, scorpionism and ophidism in Ouro Preto Municipality, Minas Gerais State, Brazil

Abstract: INTRODUCTION This retrospective study shows the profile of arachnidism, ophidism, and scorpionism in the Ouro Preto Municipality, Brazil, from January 2007 to December 2013. METHODS The data were gathered from forms of the Epidemiological Surveillance Sector of the town's Health's Municipal Secretary. RESULTS Of the 412 envenomations, 308 were caused by spiders, 78 by scorpions, and 26 by snakes. The highest number of incidents involved people aged 20-34 years. Females were more affected than males. There were no reports of death. CONCLUSIONS The results show that envenomations caused by spiders, scorpions and snakes have decreased in recent years

Search for electromagnetic properties of the neutrinos at the LHC

Exclusive production of neutrinos via photon-photon fusion provides an excellent opportunity to probe electromagnetic properties of the neutrinos at the LHC. We explore the potential of processes pp-> p gamma gamma p -> p nu anti-nu p and pp -> p gamma gamma p -> p nu anti-nu Z p to probe neutrino-photon and neutrino-two photon couplings. We show that these reactions provide more than seven orders of magnitude improvement in neutrino-two photon couplings compared to LEP limits.Comment: 11 pages, 4 tables, New backgrounds have been adde

Psychosocial profile in portuguese adolescents with chronic disease attending an outpatient department in a hospital setting

Living with a chronic disease (CD) in adolescence involves new multifaceted challenges. This study aims to conduct a psychosocial characterization of a group of adolescents with chronic diseases in a hospital setting and to compare such dimensions for the total group and for different diseases. A cross-sectional study included 135 adolescents with chronic diseases (51.9% boys; 48.1% girls), having an average age of 14±1.5 years (SD=1.5) and attending a paediatric outpatient department in a hospital setting. Statistically significant differences were found among the different chronic diseases for the variables self-regulation (adolescents with diabetes had significantly higher competencies) and multiple psychosomatic symptoms (adolescents with neurologic diseases reported significantly more complaints). Boys presented both better health-related quality of life and psychosomatic health when compared to girls. No statistically significant differences were observed for health-related quality of life, psychosomatic health, resilience, and social support. These findings bring important suggestions especially while planning interventions, which must take into account the promotion of a healthy psychosocial development, through an inclusive perspective (covering different chronic diseases), that take into consideration specific and gendered approaches. Such suggestions might help healthcare professionals to better plan interventions in order to increase their effectiveness.Fundação para a Ciência e a Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio