Effects of aerobic exercise therapy and cognitive behavioural therapy on functioning and quality of life in amyotrophic lateral sclerosis: protocol of the FACTS-2-ALS trial

Background

Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain.

Methods

We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles.

Results

Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct.

Conclusions

The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.     

Elevated levels of fibrinogen-derived endogenous citrullinated peptides in synovial fluid of rheumatoid arthritis patients

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints and the presence of autoantibodies directed against proteins containing the non-standard arginine-derived amino acid citrulline. The protein fibrinogen, which has an essential role in blood clotting, is one of the most prominent citrullinated autoantigens in RA, particularly because it can be found in the inflamed tissue of affected joints. Here, we set out to analyze the presence of citrullinated endogenous peptides in the synovial fluid of RA and arthritic control patients.

Methods

Endogenous peptides were isolated from the synovial fluid of RA patients and controls by filtration and solid phase extraction. The peptides were identified and quantified using high-resolution liquid chromatography-mass spectrometry.

Results

Our data reveal that the synovial fluid of RA patients contains soluble endogenous peptides, derived from fibrinogen, containing significant amounts of citrulline residues and, in some cases, also phosphorylated serine. Several citrullinated peptides are found to be more abundantly present in the synovial fluid of RA patients compared to patients suffering from other inflammatory diseases affecting the joints.

Conclusions

The increased presence of citrullinated peptides in RA patients points toward a possible specific role of these peptides in the immune response at the basis of the recognition of citrullinated peptides and proteins by RA patient autoantibodies.     

Sensitivity coefficients for matrix-based LCA

Background, aim, and scope  

Matrix-based life cycle assessment (LCA) is part of the standard ingredients of modern LCA tools. An important aspect of matrix-based LCA that is straightforward to carry out, but that requires a careful mathematical handling, is the inclusion of sensitivity coefficients based on differentiating the matrix-based formulas.     

Environmental Impacts of Consumption in the European Union:High-Resolution Input-Output Tables with Detailed Environmental Extensions

For developing product policy, insight into the environmental effects of products is required. But available life-cycle assessment studies (LCAs) are hardly comparable between different products and do not cover total consumption. Input-output analysis with environmental extensions (EEIOA) of full consumption is not available for the European Union. Available country studies have a low sector resolution and a limited number of environmental extensions. This study fills the gap between detailed LCA and low-resolution EEIOA, specifying the environmental effects of household consumption in the European Union, discerning nearly 500 sectors, while specifying a large number of environmental extensions. Added to the production sectors are a number of consumption activities with direct emissions, such as automobile driving, cooking and heating, and a number of postconsumer waste management sectors. The data for Europe have been constructed by using the sparse available and coarse economic and environmental data on European countries and adding technological detail mainly based on data from the United States.
A small number of products score high on environmental impact per Euro and also have a substantial share of overall consumer expenditure. Several meat and dairy products, household heating, and car driving thus have a large share of the total environmental impact. Due to their sales volume, however, products with a medium or low environmental score per Euro may also have a substantial impact. This is the case with bars and restaurants, clothing, residential construction, and even a service such as telecommunications. The limitations in real European data made heroic assumptions necessary to operationalize the model. One conclusion, therefore, is that provision of data in Europe urgently needs to be improved, at least to the level of sector detail currently available for the United States and Japan.     

Synthesis and characterization of an unusual equatorially substituted di-manganese compound. The first structural determination of a phosphite compound of type [Mn2(CO)9P]

Reaction of (acetonitrile)-nona(carbonyl)-di-manganese and tri-iso-propyl phosphite provided the new phosphite compound [Mn₂(CO)₉L]. The product was fully characterized and the molecular structure was determined by single crystal X-ray diffraction. This represents the first structural analysis of a di-manganese carbonyl compound containing phosphite ligands. In addition, this compound displays a rare example of an equatorially substituted di-manganese carbonyl compound.     

Clinical evaluation of autoantibodies to a novel PM/Scl peptide antigen

Anti-PM/Scl antibodies represent a specific serological marker for a subset of patients with scleroderma (Scl) and polymyositis (PM), and especially with the PM/Scl overlap syndrome (PM/Scl). Anti-PM/Scl reactivity is found in 24% of PM/Scl patients and is found in 3–10% of Scl and PM patients. The PM/Scl autoantigen complex comprises 11–16 different polypeptides. Many of those proteins can serve as targets of the anti-PM/Scl B-cell response, but most frequently the PM/Scl-100 and PM/Scl-75 polypeptides are targeted. In the present study we investigated the clinical relevance of a major alpha helical PM/Scl-100 epitope (PM1-α) using a newly developed peptide-based immunoassay and compared the immunological properties of this peptide with native and recombinant PM/Scl antigens. In a technical comparison, we showed that an ELISA based on the PM1-α peptide is more sensitive than common techniques to detect anti-PM/Scl antibodies such as immunoblot, indirect immunofluorescence on HEp-2 cells and ELISA with recombinant PM/Scl polypeptides. We found no statistical evidence of a positive association between anti-PM1-α and other antibodies, with the exception of known PM/Scl components. In our cohort a negative correlation could be found with anti-Scl-70 (topoisomerase I), anti-Jo-1 (histidyl tRNA synthetase) and anti-centromere proteins. In a multicenter evaluation we demonstrated that the PM1-α peptide represents a sensitive and reliable substrate for the detection of a subclass of anti-PM/Scl antibodies. In total, 22/40 (55%) PM/Scl patients, 27/205 (13.2%) Scl patients and 3/40 (7.5%) PM patients, but only 5/288 (1.7%) unrelated controls, tested positive for the anti-PM1-α peptide antibodies. These data indicate that anti-PM1-α antibodies appear to be exclusively present in sera from PM/Scl patients, from Scl patients and, to a lesser extent, from PM patients. The anti-PM1-α ELISA thus offers a new serological marker to diagnose and discriminate different systemic autoimmune disorders.     

Representing Statistical Distributions for Uncertain Parameters in LCA. Relationships between mathematical forms,their representation in EcoSpold,and their representation in CMLCA (7 pp)

Introduction Statistical information for LCA is increasingly becoming available in databases. At the same time, processing of statistical information is increasingly becoming easier by software for LCA. A practical problem is that there is no unique unambiguous representation for statistical distributions.- Representations. This paper discusses the most frequently encountered statistical distributions, their representation in mathematical statistics, EcoSpold and CMLCA, and the relationships between these representations.- The distributions. Four statistical distributions are discussed: uniform, triangular, normal and lognormal.- Software and examples. An easy to use software tool is available for supporting the conversion steps. Its use is illustrated with a simple example.Discussion This paper shows which ambiguities exist for specifying statistical distributions, and which complications can arise when uncertainty information is transferred from a database to an LCA program. This calls for a more extensive standardization of the vocabulary and symbols to express such information. We invite suppliers of software and databases to provide their parameter representations in a clear and unambiguous way and hope that a future revision of the ISO/TS 14048 document will standardize representation and terminology for statistical information.     

Caspase-mediated cleavage of the exosome subunit PM/Scl-75 during apoptosis

Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'→5' exoribonucleases that functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75, is cleaved during apoptosis. PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75 cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal part of the protein at Asp369 (IILD³⁶⁹↓G), and at least a fraction of the resulting N-terminal fragments of PM/Scl-75 remains associated with the exosome. Finally, the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed.