Chemical intolerance

Chemical intolerance (CI) is a term used to describe a condition in which the sufferer experiences a complex array of recurrent unspecific symptoms attributed to low-level chemical exposure that most people regard as unproblematic. Severe CI constitutes the distinguishing feature of multiple chemical sensitivity (MCS). The symptoms reported by CI subjects are manifold, involving symptoms from multiple organs systems. In severe cases of CI, the condition can cause considerable life-style limitations with severe social, occupational and economic consequences. As no diagnostic tools for CI are available, the presence of the condition can only be established in accordance to criteria definitions. Numerous modes of action have been suggested to explain CI, with the most commonly discussed theories involving the immune system, central nervous system, olfactory and respiratory systems as well as altered metabolic capacity, behavioral conditioning and emotional regulation. However, in spite of more than 50 years of research, there is still a great deal of uncertainties regarding the event(s) and underlying mechanism(s) behind symptom elicitation. As a result, patients are often misdiagnosed or offered health care solutions with limited or no effect, and they experience being met with mistrust and doubt by health care professionals, the social care system and by friends and relatives. Evidence-based treatment options are currently unavailable, however, a person-centered care model based on a multidisciplinary treatment approach and individualized care plans have shown promising results. With this in mind, further research studies and health care solutions should be based on a multifactorial and interdisciplinary approach.</p

A novel cell factory for efficient production of ethanol from dairy waste

BACKGROUND: Sustainable and economically feasible ways to produce ethanol or other liquid fuels are becoming increasingly relevant due to the limited supply of fossil fuels and the environmental consequences associated with their consumption. Microbial production of fuel compounds has gained a lot of attention and focus has mostly been on developing bio-processes involving non-food plant biomass feedstocks. The high cost of the enzymes needed to degrade such feedstocks into its constituent sugars as well as problems due to various inhibitors generated in pretreatment are two challenges that have to be addressed if cost-effective processes are to be established. Various industries, especially within the food sector, often have waste streams rich in carbohydrates and/or other nutrients, and these could serve as alternative feedstocks for such bio-processes. The dairy industry is a good example, where large amounts of cheese whey or various processed forms thereof are generated. Because of their nutrient-rich nature, these substrates are particularly well suited as feedstocks for microbial production. RESULTS: We have generated a Lactococcus lactis strain which produces ethanol as its sole fermentation product from the lactose contained in residual whey permeate (RWP), by introducing lactose catabolism into a L. lactis strain CS4435 (MG1363 Δ(3)ldh, Δpta, ΔadhE, pCS4268), where the carbon flow has been directed toward ethanol instead of lactate. To achieve growth and ethanol production on RWP, we added corn steep liquor hydrolysate (CSLH) as the nitrogen source. The outcome was efficient ethanol production with a titer of 41 g/L and a yield of 70 % of the theoretical maximum using a fed-batch strategy. The combination of a low-cost medium from industrial waste streams and an efficient cell factory should make the developed process industrially interesting. CONCLUSIONS: A process for the production of ethanol using L. lactis and a cheap renewable feedstock was developed. The results demonstrate that it is possible to achieve sustainable bioconversion of waste products from the dairy industry (RWP) and corn milling industry (CSLH) to ethanol and the process developed shows great potential for commercial realization

Chemosensory perception, symptoms and autonomic responses during chemical exposure in multiple chemical sensitivity

PURPOSE: Multiple chemical sensitivity (MCS) is a prevalent medically unexplained symptom characterized by symptom reactions to everyday chemical exposure below hygienic thresholds. The aim of this study was to investigate the expressions of hyper-reactivity in MCS during whole-body exposure to low concentrations of the odorant n-butanol.METHODS: We exposed 18 participants with MCS and 18 non-ill controls to a low concentration of the odorant n-butanol using an exposure chamber. The first 10 min constituted blank exposure, after which the n-butanol concentration increased and reached a plateau at 11.5 mg/m(3).RESULTS: MCS participants, compared with controls, reported greater perceived odor intensities, more unpleasantness to the exposure and increasing symptoms over time. MCS participants also expressed higher pulse rate and lower pulse rate variability than controls did. No group differences were found for breathing rate or tonic electrodermal activity responses.CONCLUSIONS: We conclude that MCS sufferers differ from healthy controls in terms of autonomic responses, symptoms and chemosensory perception during chemical exposure.</p

Splice-site mutations cause Rrp6-mediated nuclear retention of the unspliced RNAs and transcriptional down-regulation of the splicing-defective genes

Background: Eukaryotic cells have developed surveillance mechanisms to prevent the expression of aberrant transcripts. An early surveillance checkpoint acts at the transcription site and prevents the release of mRNAs that carry processing defects. The exosome subunit Rrp6 is required for this checkpoint in Saccharomyces cerevisiae, but it is not known whether Rrp6 also plays a role in mRNA surveillance in higher eukaryotes. Methodology/Principal Findings: We have developed an in vivo system to study nuclear mRNA surveillance in Drosophila melanogaster. We have produced S2 cells that express a human b-globin gene with mutated splice sites in intron 2 (mut bglobin). The transcripts encoded by the mut b-globin gene are normally spliced at intron 1 but retain intron 2. The levels of the mut b-globin transcripts are much lower than those of wild type (wt) ß-globin mRNAs transcribed from the same promoter. We have compared the expression of the mut and wt b-globin genes to investigate the mechanisms that downregulate the production of defective mRNAs. Both wt and mut b-globin transcripts are processed at the 39, but the mut bglobin transcripts are less efficiently cleaved than the wt transcripts. Moreover, the mut b-globin transcripts are less efficiently released from the transcription site, as shown by FISH, and this defect is restored by depletion of Rrp6 by RNAi. Furthermore, transcription of the mut b-globin gene is significantly impaired as revealed by ChIP experiments that measure the association of the RNA polymerase II with the transcribed genes. We have also shown that the mut b-globin gene shows reduced levels of H3K4me3. Conclusions/Significance: Our results show that there are at least two surveillance responses that operate cotranscriptionally in insect cells and probably in all metazoans. One response requires Rrp6 and results in the inefficient release of defective mRNAs from the transcription site. The other response acts at the transcription level and reduces the synthesis of the defective transcripts through a mechanism that involves histone modifications

Synthesis of (3R)-acetoin and 2,3-butanediol isomers by metabolically engineered Lactococcus lactis

The potential that lies in harnessing the chemical synthesis capabilities inherent in living organisms is immense. Here we demonstrate how the biosynthetic machinery of Lactococcus lactis, can be diverted to make (3R)-acetoin and the derived 2,3-butanediol isomers meso-(2,3)-butanediol (m-BDO) and (2R,3R)-butanediol (R-BDO). Efficient production of (3R)-acetoin was accomplished using a strain where the competing lactate, acetate and ethanol forming pathways had been blocked. By introducing different alcohol dehydrogenases into this strain, either EcBDH from Enterobacter cloacae or SadB from Achromobacter xylosooxidans, it was possible to achieve high-yield production of m-BDO or R-BDO respectively. To achieve biosustainable production of these chemicals from dairy waste, we transformed the above strains with the lactose plasmid pLP712. This enabled efficient production of (3R)-acetoin, m-BDO and R-BDO from processed whey waste, with titers of 27, 51, and 32 g/L respectively. The corresponding yields obtained were 0.42, 0.47 and 0.40 g/g lactose, which is 82%, 89%, and 76% of maximum theoretical yield respectively. These results clearly demonstrate that L. lactis is an excellent choice as a cell factory for transforming lactose containing dairy waste into value added chemicals

The BDS checklist as measure of illness severity:A cross-sectional cohort study in the Danish general population, primary care and specialised setting

Objective The bodily distress syndrome (BDS) checklist has proven to be useful in the diagnostic categorisation and as screening tool for functional somatic disorders (FSD). This study aims to investigate whether the BDS checklist total sum score (0–100) can be used as a measure of physical symptom burden and FSD illness severity.Design Cross-sectional.Setting Danish general population, primary care and specialised clinical setting.Participants A general population cohort (n=9656), a primary care cohort (n=2480) and a cohort of patients with multiorgan BDS from specialised clinical setting (n=492).Outcome measures All data were self-reported. Physical symptoms were measured with the 25-item BDS checklist. Overall self-perceived health was measured with one item from the 36-item Short-Form Health Survey (SF-36). Physical functioning was measured with an aggregate score of four items from the SF-36/SF-12 scales ‘physical functioning’, ‘bodily pain’ and ‘vitality’. Emotional distress was measured with the mental distress subscale (SCL-8) from the Danish version of the Hopkins Symptom Checklist-90. Illness worry was measured with the six-item Whiteley Index.Results For all cohorts, bifactor models established that despite some multidimensionality the total sum score of the BDS checklist adequately reflected physical symptom burden and illness severity. The BDS checklist had acceptable convergent validity with measures of overall health (r=0.25–0.58), physical functioning (r=0.22–0.58), emotional distress (r=0.47–0.62) and illness worry (r=0.36–0.55). Acceptability was good with a low number of missing responses to items (&lt;3%). Internal consistency was high (α ≥0.879). BDS score means varied and reflected symptom burden across cohorts (13.03–46.15). We provide normative data for the Danish general population.Conclusions The BDS checklist total sum score can be used as a measure of symptom burden and FSD illness severity across settings. These findings establish the usefulness of the BDS checklist in clinics and in research, both as a diagnostic screening tool and as an instrument to assess illness severity

Translation and examination of construct validity of the Danish version of the Tampa Scale for Kinesiophobia

OBJECTIVES: This study investigates the construct validity of the Danish Tampa Scale for Kinesiophobia (TSK).METHODS: The English 17-item scale was translated into Danish adhering to WHO's guidelines. The construct validity of the TSK was examined in a random general population sample of 4,884 18- to 72-year olds with pain within the past 4 weeks. Examination of construct validity adhered to the COSMIN checklist. Structural validity was examined by splitting the sample and conducting exploratory factor analysis on one half and confirmatory factor analysis on the other half. Convergent validity was examined through associations with self-report measures and objective physical performance tests. Reference scores for the TSK were calculated.RESULTS: After translation, all respondents felt confident that they understood the meaning of the items. All but one found the questionnaire acceptable. The exploratory factor analysis suggested that a 1-factor 13-item version without 4 reversed items resulted in the most consistent fit across subgroups of gender, age, and severe pain report. Five different models of the TSK were tested in the confirmatory factor analysis. While none were excellent fits, both one- and two-factor models of the TSK-13 and TSK-11 were acceptable. Two-factor models marginally outperformed one-factor models on goodness of fit. There was no association between TSK scores and muscular fitness or self-reported physical activity. Cardiorespiratory fitness, self-perceived physical fitness, and self-efficacy had weak correlations with TSK scores. Scores showed modest associations with self-report measures of anxiety, illness worry, pain interference, and daily limitations.CONCLUSIONS: Based on an overall consideration of results, we recommend using the TSK-13 as a one-dimensional construct for both research and clinical purposes pending further examinations of the TSK in clinical samples. TSK scores from the present study can serve as a standard of reference for levels of Kinesiophobia in the general population.</p