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Transthyretin (TTR) is a homotetrameric protein that transports thyroxine and retinol. Tetramer destabilization and misfolding of the released monomers result in TTR aggregation, leading to its deposition as amyloid primarily in the heart and peripheral nervous system. Over 100 mutations of TTR have been linked to familial forms of TTR amyloidosis. Considerable effort has been devoted to the study of TTR aggregation of these mutants, although the majority of TTR-related amyloidosis is represented by sporadic cases due to the aggregation and deposition of the otherwise stable wild-type (WT) protein. Heparan sulfate (HS) has been found as a pertinent component in a number of amyloid deposits, suggesting its participation in amyloidogenesis. This study aimed to investigate possible roles of HS in TTR aggregation. Examination of heart tissue from an elderly cardiomyopathic patient revealed substantial accumulation of HS associated with the TTR amyloid deposits. Studies demonstrated that heparin/HS promoted TTR fibrillization through selective interaction with a basic motif of TTR. The importance of HS for TTR fibrillization was illustrated in a cell model; TTR incubated with WT Chinese hamster ovary cells resulted in fibrillization of the protein, but not with HS-deficient cells (pgsD-677). The effect of heparin on TTR fibril formation was further demonstrated in a Drosophila model that overexpresses TTR. Heparin was colocalized with TTR deposits in the head of the flies reared on heparin-supplemented medium, whereas no heparin was detected in the nontreated flies. Heparin of low molecular weight (Klexane) did not demonstrate this effect.

Increasingly, customer companies hire external information technology (IT) consultants, often on a special project basis. These consultants are employees of professional service firms, although they receive their assignments from the hiring companies, report to them, and are supervised by them. Using semistructured interviews with 12 IT consultants in Sweden, we examine the factors that influence their work motivation, including the effect of this dual allegiance—to the service firm and to the customer company. The data indicate that the primary motivators are the variety in tasks and the opportunity to influence and/or manage an entire project. Neither monetary incentives nor the consultancy firm norms are strong motivators. A factor that affects work behavior and motivation is the subordinate identity that IT consultants must assume with their powerful clients. The article concludes with practical suggestions for managers who seek to understand what motivates employees who work at a distance, under external control. © 2011 Wiley Periodicals, Inc. © 2011 Wiley Periodicals, Inc.

The recombinant miniature spider silk protein, 4RepCT, was used to fabricate film, foam, fiber and mesh matrices of different dimensionality, microstructure and nanotopography. These matrices were evaluated regarding their suitability for cell culturing. Human primary fibroblasts attached to and grew well on all matrix types, also in the absence of serum proteins or other animal-derived additives. The highest cell counts were obtained on matrices combining film and fiber/mesh. The cells showed an elongated shape that followed the structure of the matrices and exhibited prominent actin filaments. Moreover, the fibroblasts produced, secreted and deposited collagen type I onto the matrices. These results, together with findings of the matrices being mechanically robust, hold promise not only for in vitro cell culturing, but also for tissue engineering applications.

Amyloid consists of β-sheet polymers and is associated with disease and with functional assemblies. Amyloid-forming proteins differ widely in native structures and sequences. We describe here how conformational preferences of non-polar amino acid residues can affect amyloid formation. The most non-polar residues promote either β-strands (Val, Ile, Phe, and Cys, VIFC) or α-helices (Leu, Ala, and Met, LAM), while the most polar residues promote only α-helices. For 12 proteins associated with disease, the localizations of the amyloid core regions are known. Eleven of these contain segments that are biased for VIFC, but essentially lack segments that are biased for LAM. For the amyloid β-peptide associated with Alzheimer's disease and an amyloidogenic fragment of the prion protein, observed effects of mutations support that VIFC bias favors formation of β-sheet aggregates and amyloid, while LAM bias prevents it. VIFC and LAM profiles combine information on secondary structure propensities and polarity, and add a simple criterion to the prediction of amyloidogenic regions.

Background Anastomotic leakage (AL) after oesophageal surgery is a serious complication, leading to increased postoperative mortality. Early detection and treatment is essential. The aim of this study was to investigate if inflammatory serum parameters in the early postoperative course after oesophageal cancer surgery, could predict development of an AL. Methods All patients in Sweden with AL after thoraco-abdominal surgery for oesophageal or gastroesophageal junction cancer from 2006–01-01 to 2017–01-31 were collected from the Swedish National Registry for esophageal and gastric cancer (NREV). Two matched controls for each AL-patient were also selected from the registry. Pre-, per- and postoperative variables were collected from NREV. The following parameters were collected from patient charts: number of days from surgery to AL, diagnostic modality, method of treatment, serum levels of C-reactive protein (CRP), White blood cell count (WBC) and serum-Albumin taken on postoperative day 1 to 7 (POD1–7). Thoracic- and cervical anastomosis were analysed separately. Perioperative data and inflammatory markers were compared between controls and AL-patients. Receiver Operating Characteristic (ROC) curves was constructed to identify optimal cut-off values and a multivariate analysis was performed to identify independent risk factors. Results A total of 155 patients with AL and 307 controls (n = 462) were analysed. In patients with thoracic anastomosis median levels of CRP and WBC were significantly different on POD 2–7 and on POD 4–7 comparing AL-patients to controls. In patients with cervical anastomosis there was a significant difference in WBC levels on POD 1–7. ROC-curve analysis identified CRP on POD3 (cut-off 221) and POD4 (cut-off 203) as the best candidates for predicting AL in patients with a thoracic anastomosis, displaying an area under curve of 0.754 (Sensitivity 59%, Specificity 83%) and 0.731 (Sensitivity: 57%, Specificity 82%). Conclusion In this nation-wide register study we found that a model combining S-CRP levels on POD 3 and POD 4 after a thoraco-abdominal esophagectomy, could identify patients with increased risk of anastomotic leakage several days before it was diagnosed. However, since the sensitivity of this test is relatively low for predicting AL, it must be assessed in a larger clinical context. Disclosure All authors have declared no conflicts of interest.

Spider dragline silk is an outstanding material made up of unique proteins-spidroins. Analysis of the amino acid sequences of full-length spidroins reveals a tripartite composition: an N-terminal non-repetitive domain, a highly repetitive central part composed of approximately 100 polyalanine/glycine rich co-segments and a C-terminal non-repetitive domain. Recent molecular data on the terminal domains suggest that these have different functions. The composite nature of spidroins allows for recombinant production of individual and combined regions. Miniaturized spidroins designed by linking the terminal domains with a limited number of repetitive segments recapitulate the properties of native spidroins to a surprisingly large extent, provided that they are produced and isolated in a manner that retains water solubility until fibre formation is triggered. Biocompatibility studies in cell culture or in vivo of native and recombinant spider silk indicate that they are surprisingly well tolerated, suggesting that recombinant spider silk has potential for biomedical applications.

We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high-resolution array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike. (C) 2010 Elsevier Inc. All rights reserved.

Objectives: The aim of this study was to determine whether a novel small molecule RVX-208 affects apolipoprotein (apo)A-I and high-density lipoprotein cholesterol (HDL-C) levels in vitro and in viv...

Amyloid consists of cross-beta-sheet fibrils and is associated with about 25 human diseases, including several neurodegenerative diseases, systemic and localized amyloidoses and type II diabetes mellitus. Amyloid-forming proteins differ in structures and sequences, and it is to a large extent unknown what makes them convert from their native conformations into amyloid. In this review, current understanding of amino acid sequence determinants and the effects of molecular chaperones on amyloid formation are discussed. Studies of the nonpolar, transmembrane surfactant protein C (SP-C) have revealed amino acid sequence features that determine its amyloid fibril formation, features that are also found in the amyloid beta-peptide in Alzheimer's disease and the prion protein. Moreover, a proprotein chaperone domain (CTC(Brichos)) that prevents amyloid-like aggregation during proSP-C biosynthesis can prevent fibril formation also of other amyloidogenic proteins.

RVX-208 lowers major adverse cardiovascular events (MACE) by 57% in diabetes mellitus (DM) patients from post-hoc analysis of phase 2 underpins an ongoing phase 3 BETonMACE trial. How RVX-208, an inhibitor of acetylated lysine binding to epigenetic readers called bromodomain extra-terminal (BET)

We have recently shown that it is possible to recombinantly produce a miniature spider silk protein, 4RepCT, that spontaneously self-assembles into mechanically stable macroscopic fibers (Stark, M.; Grip, S.; Rising, A.; Hedhammar, M.; Engstrom, W.; Hjalm, G.; Johansson, J. Macroscopic fibers self-assembled from recombinant miniature spider silk proteins. Biomacromolecules 2007, 8 (5), 1695-1701). When produced as a soluble fusion protein (with thioredoxin) in Escherichia coli , the spider silk protein can be subjected to several purification steps without aggregating. Here, combined purification and endotoxin removal is achieved using a simple cell wash procedure, protein affinity purification, and LPS depletion. No toxic chemicals were included in the process and the protein retained its ability to self-assemble into fibers. With this method, fibers with pyrogenicity corresponding to less than 1 EU/mg could be recovered. Moreover, the fibers could be sterilized through autoclaving with retained morphology, structure, and mechanical properties. This implies that this recombinant silk is suitable for usage as biomaterial, which is further supported by data showing that the fibers allow growth of human primary fibroblasts.

In Alzheimer's disease the amyloid beta-peptide (Abeta) aggregates in brain tissue and arteries. Abeta is proteolytically cleaved out from amyloid precursor protein (APP) by different secretases. Recently, the transmembrane protein ITM2B/Bri2, which is expressed in neurons and associated with familial British and Danish dementia, was shown to inhibit APP processing in transfected cells as well as in transgenic mice. Several mechanisms by which Bri2 can interfere with Abeta production and aggregation have been proposed. Herein, we studied recombinant human Bri2 (residues 90-236) containing the extracellular Brichos domain without the ABri23 peptide. Bri2(90-236) binds to ABri23, which suggests that these two parts interact during Bri2 biosynthesis, in line with proposed functions of Brichos domains in other proteins. Moreover, Bri2(90-236) binds Abeta1-40 and inhibits its aggregation and fibril formation. These data suggest a model for how the processing of Bri2 and APP are interrelated.

Rising demand for product means that the recycling of materials is now more important than ever, saving a lot of energy embedded in materials, thus reducing CO(2) emissions. Providing relevant info ...

ObjectivesTo assess (1) whether visual disturbances can be demonstrated with objective measures more often in patients with mild traumatic brain injury (mTBI) than in orthopaedic controls and non-injured controls, (2) whether such objectively demonstrated disturbances change over time and (3) whether self-reported visual symptoms after mTBI correlate with objectively measurable changes in visuomotor performance.DesignA prospective, controlled, observational study, with assessments planned 7–10 and 75–100 days after injury.SettingEmergency department of a general hospital in Sweden.Participants15 patients with mTBI, 15 patients with minor orthopaedic injury, 15 non-injured controls, aged 18–40 years.Outcome measuresVisual examination, including assessment of visual acuity, accommodation, eye alignment, saccades and stereoacuity. Symptom assessment using Convergence Insufficiency Symptoms Survey (CISS) and Rivermead PostConcussion Symptoms Questionnaire.ResultsAssessments were performed 4–13 and 81–322 days after injury (extended time frames for logistical reasons). No statistically significant difference was found between the mTBI and control groups regarding saccade performance and stereoacuity at any time point. The accommodative amplitude was significantly lower in the mTBI group compared with non-injured controls at baseline. 6 out of 13 patients with mTBI had accommodative insufficiency at follow-up. Near point of convergence in the mTBI group was receded at baseline and improved statistically significantly at follow-up. At baseline, patients with mTBI had significantly higher CISS score than orthopaedic and non-injured controls. For patients with mTBI, the CISS score correlated with fusional vergence.ConclusionThere were some transient measurable visual changes regarding convergence in patients with mTBI during the subacute period after the injury. Our findings of persistence of accommodative insufficiency in a considerable proportion of patients with mTBI suggest that this visual function should not be overlooked in clinical assessment.

Alzheimer's disease (AD), an age-related neurodegenerative disorder, is the most common form of dementia, and the seventh-leading cause of death in the United States. Current treatments offer only symptomatic relief; thus, there is a great need for new treatments with disease-modifying potential. One pathological hallmark of AD is so-called senile plaques, mainly made up of β-sheet-rich assemblies of 40- or 42-residue amyloid β-peptides (Aβ). Hence, inhibition of Aβ aggregation is actively explored as an option to prevent or treat AD. Congo red (CR) has been widely used as a model antiamyloid agent to prevent Aβ aggregation. Herein, we report detailed morphological studies on the effect of CR as an antiamyloid agent, by circular dichroism spectroscopy, photo-induced cross-linking reactions, and atomic force microscopy. We also demonstrate the effect of CR on a preaggregated sample of Aβ(1-40). Our result suggests that Aβ(1-40) follows a different path for aggregation in the presence of CR.

The present workforce in the mining industry is ageing, and mining companies have difficulties recruiting young people who are not particularly interested in working in the industry. Simultaneously, mining companies tend to rely on contractors that offer volume flexibility and expertise, often in a combination that is economically appealing. This makes recruitment and development of the whole of the mining workforce complex. To recruit the right workforce, mining companies and their contractors need to cooperate and improve their knowledge about both attractive and repelling work features so that they can make wiser strategic decisions based on facts. On the basis of a Swedish context, we discuss different aspects of attractive workplaces and summarise our 'lessons learned' in six recommendations dealing with general health and safety issues, work organisation, competence development, gender equality, social responsibility and outsourcing.

The aim of the study was to test the relationship between job characteristics (job demands, job control) and perceived stress (e.g., stressed, pressured, tense) with motivators (e.g., recognition, achievement, the work itself, the possibility for growth and work significance) as the mediating variable. In this cross-sectional study a web-based questionnaire survey was conducted among 380 information technology (IT) consultants at ten IT consultancy companies in Sweden. The results showed that job demand was positively related to perceived stress and that motivators mediate the relationship between job control and perceived stress. The results point to the importance of motivators among IT consultants in the framework of job stress and performance. The managers' impact on the work characteristics in the work environment is also discussed.

Alzheimer's disease (AD), an age related neurodegenerative disorder, threatens to become a major health-economic problem. Assembly of 40- or 42-residue amyloid beta-peptides (Abeta) into neurotoxic oligo-/polymeric beta-sheet structures is an important pathogenic feature in AD, thus, inhibition of this process has been explored to prevent or treat AD. The C-terminal part plays an important role in Abeta aggregation, but most Abeta aggregation inhibitors have targeted the central region around residues 16-23. Herein, we synthesized hexapeptides with varying extents of N-methylation based on residues 32-37 of Abeta, to target its C-terminal region. We measured the peptides' abilities to retard beta-sheet and fibril formation of Abeta and to reduce Abeta neurotoxicity. A penta-N-methylated peptide was more efficient than peptides with 0, 2, or 3 N-methyl groups. This penta-N-methylated peptide moreover increased life span and locomotor activity in Drosophila melanogaster flies overexpressing human Abeta(1-42).

OBJECTIVE. We re-evaluated a cohort of patients referred for reflux symptoms and objectively diagnosed with pathological reflux, with the purpose of clarifying the course of conservatively treated gastroesophageal reflux disease (GERD). MATERIAL AND METHODS. All consecutive patients with GERD diagnosed between 1984 and 1988 showing pathologic 24-h pH-metry in the interval 3.8-10% and without any previous surgery in the gastroesophageal tract were assessed for further follow-up. A total of 40 evaluable patients were followed in the years 2007-08 with endoscopy, manometry, 24-h pH-metry, Helicobacter pylori assessment and the self-administered questionnaires the GERD Impact Scale, the Reflux Disease Questionnaire, the Quality of Life in Reflux and Dyspepsia and the Medical Outcome Study Short Form-36 Health Survey. Baseline data from the 1980s were retrieved and compared with the evaluations conducted at follow-up. RESULTS. At follow-up 20.7 years (range 18.8-23.5 years) after referral, the study population showed more use of acid suppressants (p = 0.007) and increasing prevalences of esophagitis (p = 0.001) and Barrett's esophagus (p = 0.002). Esophagitis was seen in 16/40 patients (40%) at baseline and in 29/40 (72.5%) at follow-up. No significant deterioration was seen at follow-up in manometry data and in most pH data. Patients with esophagitis (ERD) were less likely to have a positive H. pylori test (hazard ratio 0.054; p = 0.002) than non-erosive (NERD) patients. Symptom evaluations showed significantly lower quality of life in the ERD group. CONCLUSIONS. After 20 years a considerable part of the cohort still experienced symptoms of reflux and showed endoscopic progression, although no significant deteriorations were seen in manometry data and in most pH-metry data. H. pylori infection was inversely associated with erosive esophagitis and this supports the hypothesis that H. pylori colonization is a protective factor against GERD.

Spider silk is an interesting biomaterial for medical applications. Recently, a method for production of recombinant spider silk protein (4RepCT) that forms macroscopic fibres in physiological solution was developed. Herein, 4RepCT and Mersilk(TM) (control) fibres were implanted subcutaneously in rats for seven days, without any negative systemic or local reactions. The tissue response, characterised by infiltration of macrophages and multinucleated cells, was similar with both fibres, while only the 4RepCT-fibres supported ingrowth of fibroblasts and newly formed capillaries. This in vivo study indicates that 4RepCT-fibres are well tolerated and could be used for medical applications, e. g., tissue engineering.

The C-terminal domain of lung surfactant protein C (CTC) precursor (proSP-C) is involved in folding of the transmembrane segment of proSP-C. CTC includes a Brichos domain with homologs in cancer- and dementia-associated proteins. Mutations in the Brichos domain cause misfolding of proSP-C and hence amyloid fibril formation in interstitial lung disease. Electrospray ionization mass spectrometry (ESI-MS) with collision-induced dissociation (CID) experiments was applied to study non-covalent interactions between human recombinant CTC or its Brichos domain, and SP-C analogs, homotripeptides and peptides designed to model amyloid fibril formation. The results show that the Brichos domain contains the peptide-binding function of CTC. In titration experiments, apparent dissociation constants (KD) were in the micromolar range where triple-valine showed the lowest KD and triple-tyrosine the highest. Non-hydrophobic peptides failed to form complexes with Brichos. CID revealed that complexes with aromatic peptide ligands are more stable in the gas phase than complexes with non-aromatic ligands. The Brichos domain was also shown to bind fibril-forming peptides containing aromatic/hydrophobic residues. Copyright © 2009 John Wiley & Sons, Ltd.

Measurement uncertainty is an important part of a measurement result that still often is neglected. A complete combined uncertainty budget can be calculated for non-routine measurements. However, for routine measurements, this work becomes time-consuming since every measurement result requires an uncertainty analysis. By analysing the uncertainty on a measurement system level in e.g. high resolution gamma spectrometry, the uncertainty analysis will be universal for a particular measurement geometry. The problem is then reduced to implementing the combined uncertainty into measurement software. This work shows how this analysis can be done and implemented into a commercial software for gamma spectrometric measurements.

The amyloid-β peptide (Aβ) can generate cytotoxic oligomers, and their accumulation is thought to underlie the neuropathologic changes found in Alzheimer's disease. Known inhibitors of Aβ polymerization bind to undefined structures and can work as nonspecific aggregators, and inhibitors that target conformations that also occur in larger Aβ assemblies may even increase oligomer-derived toxicity. Here we report on an alternative approach whereby ligands are designed to bind and stabilize the 13–26 region of Aβ in an α-helical conformation, inspired by the postulated Aβ native structure. This is achieved with 2 different classes of compounds that also reduce Aβ toxicity to cells in culture and to hippocampal slice preparations, and that do not show any nonspecific aggregatory properties. In addition, when these inhibitors are administered to Drosophila melanogaster expressing human Aβ 1–42 in the central nervous system, a prolonged lifespan, increased locomotor activity, and reduced neurodegeneration is observed. We conclude that stabilization of the central Aβ α-helix counteracts polymerization into toxic assemblies and provides a strategy for development of specific inhibitors of Aβ polymerization.

Objective: Surface activity of pulmonary surfactant is impaired by exposure to syringes lubricated with silicone oil (SO). These syringes are used daily in clinical practice. Design: In vitro experiments were used for detection of SO, determination of surface activity, and semiquantitative measurement of surfactant protein (SP)-B and -C in SO/surfactant mixtures. Randomized, controlled animal studies were applied for determination of in vivo activity. Setting: University research laboratory. Interventions: Mass spectrometry of SO originating from syringes with and without surfactant was performed. The surface activity of SO plus surfactant phospholipids (PLs) or modified natural surfactant (Curosurf) was measured. SO/Curosurf preparations were further analyzed for changes in the content of SP-B and SP-C using immunoblotting. Neonatal rabbits received mixtures of SO/Curosurf (ratio 0-1.3 mg/mg PL) intratracheally and were then ventilated with a standardized sequence of peak insufflation pressures. Tidal volume curves were recorded, gas volumes of excised lungs were measured, and histologic analysis was performed. Measurements and Main Results: Dissolved SO was found after rinsing syringes with organic solvents or Curosurf. Surface activity of Curosurf was significantly reduced after addition of 0.13-1.3 mg SO/mg PL. Immunoblotting revealed interference of SO with SP-B, but not with SP-C. With increasing SO/Curosurf ratios, patchy alveolar air expansion was observed, lung gas volumes were reduced, and time to inflate the lungs was increased, whereas compliance and tidal volumes remained unimpaired. Conclusions: In vitro SO impairs surface activity of Curosurf and leads to interference with SP-B. SO contamination of exogenous surfactant impairs lung function in animal studies and should be avoided.

Amyloid fibrils are found in approximately 25 different diseases, including Alzheimer's disease. Lung surfactant protein C (SP-C) forms fibrils in association with pulmonary disease. It was recently found that the C-terminal domain of proSP-C (CTC), which is localized to the endoplasmic reticulum (ER) lumen, protects the transmembrane (TM) part of (pro)SP-C from aggregation into amyloid until it has a folded into an alpha-helix. CTC appears to have a more general anti-amyloid effect by also acting on TM regions of other proteins. Here we investigate interactions of CTC with the amyloid beta-peptide (Abeta) associated with Alzheimer's disease and medin, a peptide that forms fibrils in the most common form of human amyloid. CTC prevents fibril formation in Abeta and medin and forms a complex with Abeta oligomers, as judged by size-exclusion chromatography and electrospray ionization mass spectrometry. These data suggest that CTC functions as a chaperone that acts preferentially against unfolded TM segments and structural motifs found during amyloid fibril formation, a mechanism that may be exploited in forming a basis for future anti-amyloid therapy.

Prosurfactant protein C (proSP-C) is a 197-residue integral membrane protein, in which the C-terminal domain (CTC, positions 59–197) is localized in the endoplasmic reticulum (ER) lumen and contains a Brichos domain (positions 94–197). Mature SP-C corresponds largely to the transmembrane (TM) region of proSP-C. CTC binds to SP-C, provided that it is in nonhelical conformation, and can prevent formation of intracellular amyloid-like inclusions of proSP-C that harbor mutations linked to interstitial lung disease (ILD). Herein it is shown that expression of proSP-C (1–58), that is, the N-terminal propeptide and the TM region, in HEK293 cells results in virtually no detectable protein, while coexpression of CTC in trans yields SDS-soluble monomeric proSP-C (1–58). Recombinant human (rh) CTC binds to cellulose-bound peptides derived from the nonpolar TM region, but not the polar cytosolic part, of proSP-C, and requires ≥5-residues for maximal binding. Binding of rhCTC to a nonhelical peptide derived from SP-C results in α-helix formation provided that it contains a long TM segment. Finally, rhCTC and rhCTC Brichos domain shows very similar substrate specificities, but rhCTCL188Q, a mutation linked to ILD is unable to bind all peptides analyzed. These data indicate that the Brichos domain of proSP-C is a chaperone that induces α-helix formation of an aggregation-prone TM region.

The aim of the present study was to investigate longitudinal relations between decision latitude, psychological workload and social support and musculoskeletal neck, shoulder and low back symptoms. In this longitudinal two-wave cohort study a questionnaire survey was conducted among female human service organization workers (n = 1690). The analyses were based on respondents who were considered free from the respective symptoms at baseline measurements, resulting in study samples of n = 741 for neck symptoms, n = 670 for shoulder symptoms, and n = 640 for low back symptoms. In general support was found for the job demand–control–(support) model. High strain work (high psychological load coupled with low decision latitude) in combination with low social support (‘iso-strain’) was related to increased risks of developing symptoms (occurrence of new episode) in all the body regions studied (neck, shoulder and low back). Relevance to industry The results indicate that, in order to minimize the occurrence of musculoskeletal symptoms, it is important to ensure that employees have adequate levels of decision latitude, to keep the workload at optimal levels, and to provide supervisor support and structures that facilitate coworker support.

The aim of the present study was to test a path model of the relation between psychological workload and neck/shoulder symptoms with general fatigue as a proposed mediating variable. In this longitudinal two-wave cohort study a questionnaire survey was conducted among female childcare workers. The analyses were based on initially symptom free participants (n=388). Two models were tested, with fatigue at baseline and at follow-up as the proposed mediators, respectively. The results indicate that appraised psychological workload is related to the development of symptoms measured at an 18-month follow-up. The results further indicate that this relation may be partially mediated by general fatigue (also measured at follow-up). The findings of the present study emphasize the importance of the psychological workload in the development of neck/shoulder symptoms among childcare workers. This means that in addition to workplace ergonomic interventions it is important also to pay attention to the psychosocial conditions in order to reduce these symptoms.

There must be a change in attitude towards end-of-life products. The view that these products pose a liability must be changed. Secondary material is valuable as raw material. Thus, activities enco ...

The Eyberg Child Behavior Inventory (ECBI) is a widely used 36-item uni-dimensional parent rating scale constructed to measure disruptive behavior problems in children. However, in an American sample a 22-item version, including three subscales, has been suggested in order to increase the usefulness of the ECBI. Two studies were conducted to test the ECBI in a Swedish sample (N = 841). The aims of Study I were (a) examine the psychometric properties of the ECBI (b) to investigate the correspondence between mothers' and fathers' ratings, and (c) to obtain Swedish norms. The aim of Study II was to test the suggested three-factor solution in the Swedish sample using a confirmatory factor analysis (CFA). The ECBI showed good psychometric properties also in the present study, and Swedish normative data is presented. The best-fitting CFA-model was identical to the previously suggested three-factor model, which thus might be a useful alternative to the 36-item version.

BACKGROUND AND AIMS: The optimal position for pH electrode placement in the diagnosis of gastroesophageal reflux disease (GERD) is unknown. The aim of this study was to evaluate the discriminatory power of targeted pH recording immediately above the squamocolumnar junction (SCJ) and to compare the results with those obtained by simultaneous recording at the conventional level for pH monitoring. SUBJECTS AND METHODS: Sixty-two patients with typical reflux symptoms and 49 asymptomatic volunteers underwent 48-h simultaneous wireless pH monitoring with two endoscopically placed pH recording capsules, one immediately above the SCJ and one at the traditional position, 6 cm above the SCJ. The diagnostic accuracy, sensitivity, and specificity of pH monitoring at the two levels were analyzed using receiver operating characteristics (ROC) curves. RESULTS: Of the 62 patients (39 men and 23 women, median age 48 yrs), 32 patients had erosive esophagitis and 30 had no endoscopic evidence of mucosal injury. Analysis of the area under the ROC curve (AUC) indicated that the total percent time with pH

The newly synthesized proSP-C (surfactant protein C precursor) is an integral ER (endoplasmic reticulum) membrane protein with a single metastable polyvaline alpha-helical transmembrane domain that comprises two-thirds of the mature peptide. More than 20 mutations in the ER-lumenal CTC (C-terminal domain of proSP-C), are associated with ILD (interstitial lung disease), and some of the mutations cause intracellular accumulation of cytotoxic protein aggregates and a corresponding decrease in mature SP-C. In the present study, we showed that: (i) human embryonic kidney cells expressing the ILD-associated mutants proSP-C(L188Q) and proSP-C(DeltaExon4) accumulate Congo Red-positive amyloid-like inclusions, whereas cells transfected with the mutant proSP-C(I73T) do not; (ii) transfection of CTC into cells expressing proSP-C(L188Q) results in a stable CTC-proSP-C(L188Q) complex, increased proSP-C(L188Q) half-life and reduced formation of Congo Red-positive deposits; (iii) replacement of the metastable polyvaline transmembrane segment with a stable polyleucine transmembrane segment likewise prevents formation of amyloid-like proSP-C(L188Q) aggregates; and (iv) binding of recombinant CTC to non-helical SP-C blocks SP-C amyloid fibril formation. These results suggest that CTC can prevent the polyvaline segment of proSP-C from promoting formation of amyloid-like deposits during biosynthesis, by binding to non-helical conformations. Mutations in the Brichos domain of proSP-C may lead to ILD via loss of CTC chaperone function.

The present cross-sectional study was performed to analyze potential risk factors for upper extremity disorders in two groups of forest machine operators driving harvesting vehicles and performing equal tasks in France ( n =18) and Norway ( n =19). This comparative design implied similar work tasks, but potentially different external work demands. Previous studies have suggested higher levels of neck and shoulder complaints among Norwegian operators compared to those of the French. This may be related to different external work demands and/or individual motor performance. Surface electromyography (EMG) of the right upper trapezius (RUT) and extensor digitorum (RED) muscles were measured continuously during 1 working day (7.5–8 h per operator) and video of body postures was recorded inside the cabin (1 h per operator). A questionnaire on external work demand factors and psychosocial stressors was used together with the collection of symptom data. A physical examination was performed on all workers. Borg's CR-10 scale of intensity of discomfort/pain was rated four times throughout the test day. The French operators reported less complaint ( p max ) in comparison with the Norwegian operators (0.3% EMG max ). No difference was found in number of periods with sustained low-level muscle activity neither in the RUT nor the RED muscle. In conclusion, our results support that the higher prevalence of discomfort/pain among the Norwegian forest machine operators may be related to organizational factors. Relevance to industry The study suggests some organizational/time aspects of forest harvesting and similar industry that should be considered in future interventions towards sustainable solutions that include good performance and reduced ergonomic risk factors.

Association studies were carried out in a sample of 86 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms at the apolipoprotein (apo) AI-CIII-AIV gene cluster on among-individual differences in plasma lipid and lipoprotein traits, the five high density lipoprotein (HDL) subclasses (2b to 3c), lipoprotein lipase (LPL) activity and presence and progression of atherosclerosis. Individuals were genotyped for four polymorphisms; 5'apoAI (G/A-75), 3'apoAI (PstI; P +/-), apoCIII (C/T1100) and apoCIII (PvuII; V +/-), using PCR-based techniques. Allele frequencies were similar in healthy individuals and patients (frequencies of alleles in combined population: 5'apoAI-A-75 = 0.14, 3'apoAI-P- = 0.05, apoCIII-T1100 = 0.27 and apoCIII-V- = 0.18). In the healthy individuals, levels of low density lipoprotein (LDL) triglycerides were significantly associated with genotypes of the apoCIII-PvuII polymorphism (p = 0.02), but no other associations were found between lipids or HDL subclasses and single polymorphisms in the apoAI-CIII-AIV gene cluster. Levels of triglycerides and very low density lipoprotein (VLDL) triglycerides were significantly higher in the presence of the haplotype defined by the presence of apoCIII-T1100 and common alleles of the other three polymorphisms, explaining 5.8% and 7.8% (p = 0.03 and 0.01), respectively, of sample variance. In the patients, no associations were found between lipids or HDL subclasses and variation at the apoAI-CIII-AIV gene cluster. Associations were also examined between levels of HDL subclasses and variation at the apoE (common isoforms), apoB (signal peptide and XbaI polymorphisms) and lipoprotein lipase (PvuII, HindIII and Serine447/Stop polymorphisms) gene loci. In the patient group only, levels of protein in HDL2b, HDL2a and HDL3b subclasses were significantly associated with genotypes of the LPL-HindIII polymorphism (22.1, 19.3 and 11.4%, respectively, of sample variance; p < 0.05). Finally, associations were examined between genotypes at the apoAI-CIII-AIV gene cluster and the extent of coronary atherosclerosis. Global severity of atherosclerosis at the first angiography was weakly associated with genotypes of the apoCIII-C/T1100 polymorphism, presence of the T1100 allele being associated with 53% lower median score (1.6 vs 0.75; p = 0.09).(ABSTRACT TRUNCATED AT 400 WORDS)

The aim of the present study was to investigate the relations between psychological and physical workload and musculoskeletal neck, shoulder and upper back symptoms. In this longitudinal two-phase cohort study a survey was con- ducted among non-managerial female elderly-care workers (n = 553). The analyses were based on respondents who were considered free from the respective symptoms at initial ratings, resulting in study samples of n = 230 for neck symptoms, n = 211 for shoulder symptoms, n = 400 for upper back symptoms, and n = 204 for low back symptoms. The results indi- cate that psychological workload is related to the development of musculoskeletal (neck and upper back) symptoms measured at an 18-month follow-up, both in itself and in combination with physical workload. The most important finding was that psychological workload shows significant temporal relations to neck and upper back symptoms.

The aim was to test a structural model of the relations between psychological and mechanical workload and musculoskeletal neck/shoulder symptoms. This two-wave longitudinal cohort study was based on a questionnaire survey among Swedish female child-care workers (n=789). Two models were tested using structural equation modelling, one containing only those participants considered symptom free at baseline, thus focusing on symptom development, and one containing all participants irrespective of their baseline musculoskeletal status. The results indicate that psychological workload was related to the development of neck/shoulder symptoms, and thus highlight the importance of addressing psychosocial work environment factors in organization design and workplace interventions. However, psychological workload was not related to symptoms (when controlling for baseline mechanical workload and symptoms) in the model not distinguishing between different symptoms processes. These findings point to the importance of distinguishing between different processes such as development, maintenance and recovery from symptoms in studies of workplace factors and musculoskeletal symptoms. Mechanical workload was not related to neck/shoulder symptoms, when controlling for baseline psychological workload and symptoms, in any of the models tested. No interaction effect was found for psychological and mechanical workload on neck/shoulder symptoms.

• Summary: Working in residential group care is a complex task. There is a wide gap between principles and guidelines and daily practice. This qualitative case study in a home for the long-term care and treatment of young persons in Sweden is an attempt to explore and systematize careworkers' ideas about the treatment of individual young persons. The aims were to examine personal approaches to treatment and to explore the consistency and individualization in the perceptions of the treatment of each young person. Each careworker was interviewed about each young person in two different occasions. Statements were coded and grouped into categories. • Findings: It was possible to find a model in which careworkers' treatment perceptions could be studied and compared. Each careworker had a unique and stable pattern of treatment perceptions. These perceptions of treatment were however consistent enough to create different patterns in the cases of different young persons, that is, the perception of treatment was individualized. • Applications : A well-functioning system or model of treatment ideas may be a means to enhance the quality of residential care on the assumption that the system or model is close to the real world of careworkers. It could also be means for defining treatment components and measuring treatment fidelity.

Surfactant protein C (SP-C) constitutes the transmembrane part of prosurfactant protein C (proSP-C) and is α-helical in its native state. The C-terminal part of proSP-C (CTC) is localized in the endoplasmic reticulum lumen and binds to misfolded (β-strand) SP-C, thereby preventing its aggregation and amyloid fibril formation. In this study, we investigated the structure of recombinant human CTC and the effects of CTC–membrane interaction on protein structure. CTC forms noncovalent trimers and supratrimeric oligomers. It contains two intrachain disulfide bridges, and its secondary structure is significantly affected by urea or heat only after disulfide reduction. The postulated Brichos domain of CTC, with homologs found in proteins associated with amyloid and proliferative disease, is up to 1000-fold more protected from limited proteolysis than the rest of CTC. The protein exposes hydrophobic surfaces, as determined by CTC binding to the environment-sensitive fluorescent probe 1,1′-bis(4-anilino-5,5′-naphthalenesulfonate). Fluorescence energy transfer experiments further reveal close proximity between bound 1,1′-bis(4-anilino-5,5′-naphthalenesulfonate) and tyrosine residues in CTC, some of which are conserved in all Brichos domains. CTC binds to unilamellar phospholipid vesicles with low micromolar dissociation constants, and differential scanning calorimetry and CD analyses indicate that membrane-bound CTC is less structurally ordered than the unbound protein. The exposed hydrophobic surfaces and the structural disordering that result from interactions with phospholipid membranes suggest a mechanism whereby CTC binds to misfolded SP-C in the endoplasmic reticulum membrane.

Residential care in Sweden has undergone great change in recent decades. With new small family-style institutions, the boundaries between residential care and foster care have been blurred. Almost all residential care used to be run by the public sector. Today about 80 per cent is privately run. This study compares three different settings in residential care: institutions run by the public sector, privately run institutions and family-style homes. Among other things, it is found that the institutions run by the public sector have better educated staff and a higher staff–resident ratio than privately run institutions. Despite this, they are more restrictive in their intake and they have youths with fewer problems, especially delinquency and other antisocial behaviour. The results are discussed in relation to developments in the residential care sector in Sweden and in relation to the balance between care and treatment.

Strength, elasticity, and biocompatibility make spider silk an attractive resource for the production of artificial biomaterials. Spider silk proteins, spidroins, contain hundreds of repeated poly alanine/glycine-rich blocks and are difficult to produce recombinantly in soluble form. Most previous attempts to produce artificial spider silk fibers have included solubilization steps in nonphysiological solvents. It is here demonstrated that a miniature spidroin from a protein in dragline silk of Euprosthenops australis can be produced in a soluble form in Escherichia coli when fused to a highly soluble protein partner. Although this miniature spidroin contains only four poly alanine/glycine-rich blocks followed by a C-terminal non-repetitive domain, meter-long fibers are spontaneously formed after proteolytic release of the fusion partner. The structure of the fibers is similar to that of dragline silks, and although self-assembled from recombinant proteins they are as strong as fibers spun from redissolved silk. Moreover, the fibers appear to be biocompatible because human tissue culture cells can grow on and attach to the fibers. These findings enable controlled production of high-performance biofibers at large scale under physiological conditions.

Esophageal pH monitoring using a wireless pH capsule has been suggested to generate less adverse symptoms resulting in improved patient acceptance compared with the catheter-based method although evidence to support this assumption is lacking. The aim of this study was to evaluate and compare the subjective experience of patients undergoing both techniques for esophageal pH monitoring.Using a randomized study design, patients referred for esophageal pH testing underwent both wireless and traditional catheter-based 24-h pH recording with a 7-day interval. The wireless pH capsule was placed during endoscopy and followed by 48-h pH recording. All patients answered a questionnaire, including a 10-cm visual analog scale (VAS), which described the perceived severity of symptoms and the degree of interference with normal daily activities during the pH tests.Thirty-one patients, 16 women and 15 men, were included in the analysis. The severity of all adverse symptoms associated with the wireless technique was significantly lower compared with the catheter-based technique (median VAS 2.1 vs 5.1, P0.001). Wireless pH recording was associated with less interference with off-work activities and normal daily life, median VAS 0.6 and 0.7 compared with 5.0 and 5.7, respectively, for the catheter-based technique (P0.0001). Patients actively working during both tests reported less interference with normal work during the capsule-based test than during the catheter-based pH test (median VAS 0.3 vs 6.8, P= 0.005). Twenty-seven patients (87%) stated that, if they had to undergo esophageal pH monitoring again, they preferred the wireless test over the catheter-based pH test (P0.0001).This randomized study showed that a significant majority of patients undergoing esophageal pH monitoring preferred the wireless pH capsule over the traditional catheter-based technique because of less adverse symptoms and less interference with normal daily life.

The aim of the current study was to test a structural model of the relationship between job characteristics (job demand, job control) and perceived stress (e.g. stressed, pressed, tense) with ‘motivators’ (e.g. responsibility, recognition, achievement, possibility of growth) as the mediating variable. In this cross-sectional study a web-based questionnaire survey was conducted among information technology (IT) consultants in Sweden ( N =167). The results show that job demand was positively related to perceived stress. The results further indicate that motivators in part mediate the relation between job control and perceived stress, i.e. high job control was significantly related to high appraisals of motivators, and motivators was negatively related to perceived stress. Relevance to industry The results point out the importance of motivators (e.g. responsibility, recognition, achievement, possibility of growth) among IT-consultants in the job stress and performance framework.

Background: Modified natural surfactants currently used for treatment of respiratory distress syndrome contain about 0.5–1% (w/w phospholipids) of each of the surfactant proteins SP-B and SP-C. The supply of these preparations is limited and synthetic surfactant preparations containing lipids and peptides are under development. Objectives: To investigate the potential of different concentrations of the SP-C analogue SP-C33 in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (68:31, w/w). Methods: Surface activity was evaluated in pulsating and captive bubble surfactometers and in immature newborn rabbits. Results: Preparations containing ≧1% SP-C33 achieve minimum surface tension Conclusions: These data suggest that SP-C33 is similarly efficient as the native peptide in improving surface properties of phospholipids mixtures and in increasing lung compliance in surfactant-deficient states, but that other components are needed to maintain alveolar stability at low airway pressures.

Many proteins can form amyloid-like fibrils in vitro, but only about 30 amyloids are linked to disease, whereas some proteins form physiological amyloid-like assemblies. This raises questions of how the formation of toxic protein species during amyloidogenesis is prevented or contained in vivo. Intrinsic chaperoning or regulatory factors can control the aggregation in different protein systems, thereby preventing unwanted aggregation and enabling the biological use of amyloidogenic proteins. The molecular actions of these chaperones and regulators provide clues to the prevention of amyloid disease, as well as to the harnessing of amyloidogenic proteins in medicine and biotechnology.

Different degrees of eye dominance may need to be considered when comparing monocular and binocular performance or estimating binocular summation effects. The purpose of this study was to explore eye dominance under binocular viewing conditions and observe gradual differences in preference. Two binocular eye-dominance tests were evaluated and compared to the hole-in-the-card sighting test. The first experiment was based on a binocular sighting test. The second originated from the variable-angle mirror test, utilizing physiological diplopia to determine which eye dominates the binocular percept. The participants were 32 healthy subject with normal sight. For both experiments there were plausible effects of different degrees of eye dominance affecting how the subjects positioned or perceived the scene. The outcomes were supported by a statistically significant correlation with an interocular difference in sensitivity to degraded visibility. A statistically significant correlation was found between the hole-in-the-card test and the variable-angle mirror test (r = 0.527, plt; 0.01). The experiments confirm the plausible occurrence of forms of eye dominance under binocular viewing conditions. The correlation with the hole-in-the-card test was weak to moderate, due to factors that appear to be related to testing and viewing conditions. Interocular differences in sensitivity to blur appear to be a useful factor in further grading of eye dominance.

Surfactant protein C (SP-C) is a novel amyloid protein found in the lung tissue of patients suffering from interstitial lung disease (ILD) due to mutations in the gene of the precursor protein pro-SP-C. SP-C is a small α-helical hydrophobic protein with an unusually high content of valine residues. SP-C is prone to convert into β-sheet aggregates, forming amyloid fibrils. Nature's way of solving this folding problem is to include a BRICHOS domain in pro-SP-C, which functions as a chaperone for SP-C during biosynthesis. Mutations in the pro-SP-C BRICHOS domain or linker region lead to amyloid formation of the SP-C protein and ILD. In this study, we used an in vitro transcription/translation system to study translocon-mediated folding of the WT pro-SP-C poly-Val and a designed poly-Leu transmembrane (TM) segment in the endoplasmic reticulum (ER) membrane. Furthermore, to understand how the pro-SP-C BRICHOS domain present in the ER lumen can interact with the TM segment of pro-SP-C, we studied the membrane insertion properties of the recombinant form of the pro-SP-C BRICHOS domain and two ILD-associated mutants. The results show that the co-translational folding of the WT pro-SP-C TM segment is inefficient, that the BRICHOS domain inserts into superficial parts of fluid membranes, and that BRICHOS membrane insertion is promoted by poly-Val peptides present in the membrane. In contrast, one BRICHOS and one non-BRICHOS ILD-associated mutant could not insert into membranes. These findings support a chaperone function of the BRICHOS domain, possibly together with the linker region, during pro-SP-C biosynthesis in the ER. Background: Amyloidogenic human lung surfactant protein C (SP-C) is a transmembrane peptide generated from pro-SP-C, containing a luminal BRICHOS domain. Results: BRICHOS inserts partly in ER membranes, binds unfolded SP-C, and prevents misfolding. Conclusion: Disease-associated pro-SP-C mutations result in loss of membrane insertion and binding to SP-C. Significance: Co-translational folding of transmembrane pro-SP-C is inefficient and membrane insertion of BRICHOS promotes correct folding.