Validation of the International Classification of Functioning, Disability and Health (ICF) Core Set for rheumatoid arthritis from the patient perspective using focus groups

Functioning is recognized as an important study outcome in rheumatoid arthritis (RA). The Comprehensive ICF Core Set for RA is an application of the International Classification of Functioning, Disability and Health (ICF) of the World Health Organisation with the purpose of representing the typical spectrum of functioning of patients with RA. To strengthen the patient perspective, persons with RA were explicitly involved in the validation of the Comprehensive ICF Core Set for RA using qualitative methodology. The objective of the study was twofold: to come forward with a proposal for the most appropriate methodology to validate Comprehensive ICF Core Sets from the patient perspective; and to add evidence to the validation of the Comprehensive ICF Core Set for RA from the perspective of patients. The specific aims were to explore the aspects of functioning and health important to patients with RA using two different focus group approaches (open approach and ICF-based approach) and to examine to what extent these aspects are represented by the current version of the Comprehensive ICF Core Set for RA. The sampling of patients followed the maximum variation strategy. Sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. The meaning condensation procedure was used for the data analysis. After qualitative data analysis, the resulting concepts were linked to ICF categories according to established linking rules. Forty-nine patients participated in ten focus groups (five in each approach). Of the 76 ICF categories contained in the Comprehensive ICF Core Set for RA, 65 were reported by the patients based on the open approach and 71 based on the ICF-based approach. Sixty-six additional categories (open approach, 41; ICF-based approach, 57) that are not covered in the Comprehensive ICF Core Set for RA were raised. The existing version of the Comprehensive ICF Core Set for RA could be confirmed almost entirely by the two different focus group approaches applied. Focus groups are a highly useful qualitative method to validate the Comprehensive ICF Core Set for RA from the patient perspective. The ICF-based approach seems to be the most appropriate technique.     

Identification of relevant ICF categories for indication, intervention planning and evaluation of health resort programs: a Delphi exercise

Health resort programs have a long tradition, mainly in European countries and Japan. They rely on local resources and the physical environment, physical medicine interventions and traditional medicine to optimise functioning and health. Arguably because of the long tradition, there is only a limited number of high-quality studies that examine the effectiveness of health resort programs. Specific challenges to the evaluation of health resort programs are to randomise the holistic approach with a varying number of specific interventions but also the reliance on the effect of the physical environment. Reference standards for the planning and reporting of health resort studies would be highly beneficial. With the International Classification of Functioning Disability and Health (ICF), we now have such a standard that allows us to describe body functions and structures, activities and participation and interaction with environmental factors. A major challenge when applying the ICF in practice is its length. Therefore, the objective of this project was to identify the ICF categories most relevant for health resort programs. We conducted a consensus-building, three-round, e-mail survey using the Delphi technique. Based on the consensus of the experts, it was possible to come up with an ICF Core Set that can serve as reference standards for the indication, intervention planning and evaluation of health resort programs. This preliminary ICF Core Set should be tested in different regions and in subsets of health resort visitors with varying conditions.     

Identification and bioinformatic analysis of the membrane proteins of synechocystis sp. PCC 6803

Background  

The membranes of Synechocystis sp. PCC 6803 play a central role in photosynthesis, respiration and other important metabolic pathways. Comprehensive identification of the membrane proteins is of importance for a better understanding of the diverse functions of its unique membrane structures. Up to date, approximately 900 known or predicted membrane proteins, consisting 24.5% of Synechocystis sp. PCC 6803 proteome, have been indentified by large-scale proteomic studies.     

Multiple independent evolutionary solutions to core histone gene regulation

Background  

Core histone genes are periodically expressed along the cell cycle and peak during S phase. Core histone gene expression is deeply evolutionarily conserved from the yeast Saccharomyces cerevisiae to human.     

Risk Identification and Prediction of Coal Workers’ Pneumoconiosis in Kailuan Colliery Group in China: A Historical Cohort Study

Background

Prior to 1970, coal mining technology and prevention measures in China were poor. Mechanized coal mining equipment and advanced protection measures were continuously installed in the mines after 1970. All these improvements may have resulted in a change in the incidence of coal workers’ pneumoconiosis (CWP). Therefore, it is important to identify the characteristics of CWP today and trends for the incidence of CWP in the future.

Methodology/Principal Findings

A total of 17,023 coal workers from the Kailuan Colliery Group were studied. A life-table method was used to calculate the cumulative incidence rate of CWP and predict the number of new CWP patients in the future. The probability of developing CWP was estimated by a multilayer perceptron artificial neural network for each coal worker without CWP. The results showed that the cumulative incidence rates of CWP for tunneling, mining, combining, and helping workers were 31.8%, 27.5%, 24.2%, and 2.6%, respectively, during the same observation period of 40 years. It was estimated that there would be 844 new CWP cases among 16,185 coal workers without CWP within their life expectancy. There would be 273.1, 273.1, 227.6, and 69.9 new CWP patients in the next <10, 10-, 20-, and 30- years respectively in the study cohort within their life expectancy. It was identified that coal workers whose risk probabilities were over 0.2 were at high risk for CWP, and whose risk probabilities were under 0.1 were at low risk.

Conclusion/Significance

The present and future incidence trends of CWP remain high among coal workers. We suggest that coal workers at high risk of CWP undergo a physical examination for pneumoconiosis every year, and the coal workers at low risk of CWP be examined every 5 years.     

A comprehensive characterisation of the fibre composition and properties of a limb (<Emphasis Type="Italic">Flexor digitorum superficialis,membri thoraci</Emphasis>) and a trunk (<Emphasis Type="Italic">Psoas major</Emphasis>) muscle in cattle

Background  

The fibre type attributes and the relationships among their properties play an important role in the differences in muscle capabilities and features. Comprehensive characterisation of the skeletal muscles should study the degree of association between them and their involvement in muscle functionality. The purposes of the present study were to characterise the fibre type composition of a trunk (Psoas major, PM) and a limb (Flexor digitorum, membri thoraci, FD) muscle in the bovine species and to study the degree of coordination among contractile, metabolic and histological properties of fibre types. Immunohistochemical, histochemical and histological techniques were used.     

Giardia Cyst Wall Protein 1 Is a Lectin That Binds to Curled Fibrils of the GalNAc Homopolymer

The infectious and diagnostic stage of Giardia lamblia (also known as G. intestinalis or G. duodenalis) is the cyst. The Giardia cyst wall contains fibrils of a unique β-1,3-linked N-acetylgalactosamine (GalNAc) homopolymer and at least three cyst wall proteins (CWPs) composed of Leu-rich repeats (CWP_LRR) and a C-terminal conserved Cys-rich region (CWP_CRR). Our goals were to dissect the structure of the cyst wall and determine how it is disrupted during excystation. The intact Giardia cyst wall is thin (∼400 nm), easily fractured by sonication, and impermeable to small molecules. Curled fibrils of the GalNAc homopolymer are restricted to a narrow plane and are coated with linear arrays of oval-shaped protein complex. In contrast, cyst walls of Giardia treated with hot alkali to deproteinate fibrils of the GalNAc homopolymer are thick (∼1.2 µm), resistant to sonication, and permeable. The deproteinated GalNAc homopolymer, which forms a loose lattice of curled fibrils, is bound by native CWP1 and CWP2, as well as by maltose-binding protein (MBP)-fusions containing the full-length CWP1 or CWP1_LRR. In contrast, neither MBP alone nor MBP fused to CWP1_CRR bind to the GalNAc homopolymer. Recombinant CWP1 binds to the GalNAc homopolymer within secretory vesicles of Giardia encysting in vitro. Fibrils of the GalNAc homopolymer are exposed during excystation or by treatment of heat-killed cysts with chymotrypsin, while deproteinated fibrils of the GalNAc homopolymer are degraded by extracts of Giardia cysts but not trophozoites. These results show the Leu-rich repeat domain of CWP1 is a lectin that binds to curled fibrils of the GalNAc homopolymer. During excystation, host and Giardia proteases appear to degrade bound CWPs, exposing fibrils of the GalNAc homopolymer that are digested by a stage-specific glycohydrolase.     

Macrolide use in the previous years is associated with failure to eradicate Helicobacter pylori with clarithromycin‐containing regimens

Background

There is some evidence that prior use of macrolide antibiotics is a useful predictor of the likelihood of standard triple therapy failure in Helicobacter pylori eradication. In this study, we have evaluated whether previous intake of macrolides correlates with failure to eradicate H. pylori using two different first‐line clarithromycin‐containing regimens.

Materials and Methods

Retrospective study of 212 patients with H. pylori infection treated with one of two first‐line clarithromycin‐containing regimens: 108 patients treated with triple therapy for 10 days and 104 patients treated with concomitant therapy for 10 days. The intake of macrolides (clarithromycin, azithromycin, and other macrolides) prior to the eradication therapy was obtained from the electronic medical record, which contains information regarding all the medication prescribed to the patients since the year 2004.

Results

One hundred of 212 patients (47.2%) had received at least one treatment with macrolides during the years prior to the eradication therapy. H. pylori eradication rates were significantly lower in patients with previous use compared to patients without previous use of macrolides, both with triple therapy (60.8% vs 92.9%; P < .0001) and with concomitant therapy (85.7% vs 98.2%; P = .024).

Conclusions

Previous use of macrolides correlates with a low H. pylori eradication rate with triple and concomitant clarithromycin‐containing regimens. In addition, our study shows that in patients without previous use of macrolides, triple therapy achieves per‐protocol eradication rates over 90%.     

Improving gene set analysis of microarray data by SAM-GS

Background  

Gene-set analysis evaluates the expression of biological pathways, or a priori defined gene sets, rather than that of individual genes, in association with a binary phenotype, and is of great biologic interest in many DNA microarray studies. Gene Set Enrichment Analysis (GSEA) has been applied widely as a tool for gene-set analyses. We describe here some critical problems with GSEA and propose an alternative method by extending the individual-gene analysis method, Significance Analysis of Microarray (SAM), to gene-set analyses (SAM-GS).     

The Association between Chronic Widespread Musculoskeletal Pain,Depression and Fatigue Is Genetically Mediated

Background

Chronic widespread muscoloskeletal pain (CWP) is prevalent in the general population and associated with high health care costs, so understanding the risk factors for chronic pain is important for both those affected and for society. In the present study we investigated the underlying etiological structure of CWP to understand better the association between the major clinical features of fatigue, depression and dihydroepiandrosterone sulphate (DHEAS) using a multivariate twin design.

Methodology/Principle Findings

Data were available in 463 UK female twin pairs including CWP status and information on depression, chronic fatigue and serum DHEAS levels. High to moderate heritabilities for all phenotypes were obtained (42.58% to 74.24%). The highest phenotypic correlation was observed between fatigue and CWP (r = 0.45), and the highest genetic correlation between CWP and fatigue (r_g = 0.78). Structural equation modeling revealed the AE Cholesky model to provide the best model of the observed data. In this model, two additive genetic factors could be detected loading heavily on CWP—A2 explaining 40% of the variance and A3 20%. The factor loading heaviest on DHEAS showed only a small loading on the other phenotypes and none on fatigue at all. Furthermore, one distinct non-shared environmental factor loading specifically on CWP—but not on any of the other phenotypes—could be detected suggesting that the association between CWP and the other phenotypes is due only to genetic factors.

Conclusions/Significance

Our results suggest that CWP and its associated features share a genetic predisposition but that they are relatively distinct in their environmental determinants.     

Polymorphisms in Inflammasome Genes and Risk of Coal Workers' Pneumoconiosis in a Chinese Population

Background

Coal workers'' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which triggers caspase 1-mediated IL-1β and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.

Methods

We performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1β, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.

Results

The NLRP3 rs1539019 TT genotype was associated with a significantly increased risk of CWP (adjusted odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.07–1.81), compared with the GG/GT genotype, in particular among smokers (adjusted OR = 1.67, 95%CI = 1.15–2.42). In addition, the polymorphism was significantly associated with risk of CWP patients with stage I.

Conclusions

This is the first report showing an association between the NLRP3 rs1539019 polymorphism and CWP, and suggests that this polymorphism may confer increased risk for the development of the disease. Further studies are warranted to confirm our findings.     

<Emphasis Type="Italic">Acanthamoeba</Emphasis> produces disseminated infection in locusts and traverses the locust blood-brain barrier to invade the central nervous system

Background  

Many aspects of Acanthamoeba granulomatous encephalitis remain poorly understood, including host susceptibility and chronic colonization which represent important features of the spectrum of host-pathogen interactions. Previous studies have suggested locusts as a tractable model in which to study Acanthamoeba pathogenesis. Here we determined the mode of parasite invasion of the central nervous system (CNS).     

Normal histone modifications on the inactive X chromosome in ICF and Rett syndrome cells: implications for methyl-CpG binding proteins

Background  

In mammals, there is evidence suggesting that methyl-CpG binding proteins may play a significant role in histone modification through their association with modification complexes that can deacetylate and/or methylate nucleosomes in the proximity of methylated DNA. We examined this idea for the X chromosome by studying histone modifications on the X chromosome in normal cells and in cells from patients with ICF syndrome (Immune deficiency, Centromeric region instability, and Facial anomalies syndrome). In normal cells the inactive X has characteristic silencing type histone modification patterns and the CpG islands of genes subject to X inactivation are hypermethylated. In ICF cells, however, genes subject to X inactivation are hypomethylated on the inactive X due to mutations in the DNA methyltransferase (DNMT3B) genes. Therefore, if DNA methylation is upstream of histone modification, the histones on the inactive X in ICF cells should not be modified to a silent form. In addition, we determined whether a specific methyl-CpG binding protein, MeCP2, is necessary for the inactive X histone modification pattern by studying Rett syndrome cells which are deficient in MeCP2 function.     

Proteome characterization of cassava (<Emphasis Type="Italic">Manihot esculenta</Emphasis> Crantz) somatic embryos,plantlets and tuberous roots

Background  

Proteomics is increasingly becoming an important tool for the study of many different aspects of plant functions, such as investigating the molecular processes underlying in plant physiology, development, differentiation and their interaction with the environments. To investigate the cassava (Manihot esculenta Crantz) proteome, we extracted proteins from somatic embryos, plantlets and tuberous roots of cultivar SC8 and separated them by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).     

Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial

Background

In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated.

Methods/Design

A multi-centre, assessor-blinded, randomized controlled trial is conducted. A sample of 75 FSHD patients with severe chronic fatigue (CIS-fatigue ≥ 35) will be recruited and randomized to one of three groups: (1) AET + usual care, (2) CBT + usual care or (3) usual care alone, which consists of no therapy at all or occasional (conventional) physical therapy. After an intervention period of 16 weeks and a follow-up of 3 months, the third (control) group will as yet be randomized to either AET or CBT (approximately 7 months after inclusion). Outcomes will be assessed at baseline, immediately post intervention and at 3 and 6 months follow up.

Discussion

The FACTS-2-FSHD study is the first theory-based randomized clinical trial which evaluates the effect and the maintenance of effects of AET and CBT on the reduction of chronic fatigue in patients with FSHD. The interventions are based on a theoretical model of chronic fatigue in patients with FSHD. The study will provide a unique set of data with which the relationships between outcome measures at all levels of the ICF could be assessed.

Trial registration

Dutch Trial Register, NTR1447.

     

Analysing Betula litwinowii encroachment and reforestation in the Kazbegi region,Greater Caucasus,Georgia

Aims

The encroachment of tree and shrub species in high mountains is an increasing worldwide phenomenon, which is expected to dramatically alter high‐mountain ecosystems and their functioning. Moreover it indicates in some cases a reforestation process, which will result in important ecological and social benefits, including carbon sequestration and protection against landslides. We therefore examined the spatial extent of forest growth and shrub encroachment mainly of birch (Betula litwinowii) in the sub‐alpine belt of the Central Greater Caucasus between 1987 and 2010 and its relation to topographic site conditions.

Location

Kazbegi district, Central Greater Caucasus, Georgia.

Methods

We analysed 155 vegetation relevés sampled in 2009, 2011 and 2015, mainly derived from the Caucasus Vegetation Database, to obtain information about topographic site conditions and structure of B. litwinowii stands. B. litwinowii forest growth was assessed by digitizing the forest outlines from aerial and space‐borne imagery (1987, 2005 and 2010). To identify areas of B. litwinowii encroachment as an indicator for different encroachment stages, we modelled the tree and shrub cover using the Random Forest algorithm.

Results

We found four types of B. litwinowii stands, characterized by different tree and shrub coverage (initial Bromus variegatus–Betula litwinowii encroachment indicating the first stage of succession, Aconitum nasutum–Betula litwinowii forest, Rubus idaeus–Betula litwinowii forest and Rhododendron caucasicum–Betula litwinowii tree line scrubs). B. litwinowii forest increased 25% compared to 1987 mainly in an uphill direction. Furthermore the modelled tree and shrub cover (R² = .69) could be related to the four vegetation types.

Conclusions

Our results indicate a recent trend towards shrub encroachment and consequently reforestation in the Kazbegi region.