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Objective The heterogeneity of systemic lupus erythematosus (SLE) constitutes clinical and therapeutical challenges. We therefore studied whether unrecognized disease subgroups can be identified by using autoantibody profiling together with HLA-DRB1 alleles and immunological and clinical data. Methods An unsupervised cluster analysis was performed based on detection of 13 SLE-associated autoantibodies (double-stranded DNA, nucleosomes, ribosomal P, ribonucleoprotein [RNP] 68, RNPA, Smith [Sm], Sm/RNP, Sjogren's syndrome antigen A [SSA]/Ro52, SSA/Ro60, Sjogren's syndrome antigen B [SSB]/La, cardiolipin [CL]-Immunoglobulin G [IgG], CL-Immunoglobulin M [IgM], and β2 glycoprotein I [β2 GPI]-IgG) in 911 patients with SLE from two cohorts. We evaluated whether each SLE subgroup is associated with HLA-DRB1 alleles, clinical manifestations (n = 743), and cytokine levels in circulation (n = 446). Results Our analysis identified four subgroups among the patients with SLE. Subgroup 1 (29.3%) was dominated by anti-SSA/Ro60/Ro52/SSB autoantibodies and was strongly associated with HLA-DRB1*03 (odds ratio [OR] = 4.73; 95% confidence interval [CI] = 4.52-4.94). Discoid lesions were more common for this disease subgroup (OR = 1.71, 95% CI = 1.18-2.47). Subgroup 2 (28.7%) was dominated by anti-nucleosome/SmRNP/DNA/RNPA autoantibodies and associated with HLA-DRB1*15 (OR = 1.62, 95% CI = 1.41-1.84). Nephritis was most common in this subgroup (OR = 1.61, 95% CI = 1.14-2.26). Subgroup 3 (23.8%) was characterized by anti-s2 GPI-IgG/anti-CL-IgG/IgM autoantibodies and a higher frequency of HLA-DRB1*04 compared with the other patients with SLE. Vascular events were more common in Subgroup 3 (OR = 1.74, 95% CI = 1.2-2.5). Subgroup 4 (18.2%) was negative for the investigated autoantibodies, and this subgroup was not associated with HLA-DRB1. Additionally, the levels of eight cytokines significantly differed among the disease subgroups. Conclusion Our findings suggest that four fairly distinct subgroups can be identified on the basis of the autoantibody profile in SLE. These four SLE subgroups differ regarding associations with HLA-DRB1 alleles and immunological and clinical features, suggesting dissimilar disease pathways.

A major part of the European Union’s (EU) project Sustainable Intelligent Mining System (SIMS) is investigating the development of diesel-free/carbon-neutral underground mines in order to ensure sustainable underground mining in the future. Replacing diesel machines with electric vehicles in underground hard rock mines has been widely acknowledged by the mining industry worldwide as a critical step to improve working conditions by reducing diesel exhaust related contaminants, to reduce mine ventilation electrical power cost by reducing mine airflow quantity, and to reduce mine greenhouse gas emissions. All of these are major requirements to achieve sustainable future underground mining practices. A field trial of Epiroc’s 2nd generation of Battery Electric Vehicles (BEVs) at Agnico Eagle Finland’s Kittilä mine was conducted during 2019 – 2020. Vehicles tested were MT42 mine truck, ST14 Load-Haul-Dump (LHD), and Boomer E2 jumbo drill rig. This paper outlines the improvement of the working conditions observed in the field trial, and the opinions of the mine personnel at Kittilä mine on using BEVs instead of diesel machines. Measurements of atmospheric contaminants and air temperatures taken during the field trial clearly demonstrated a significant improvement of working conditions when BEVs were operating as opposed to diesel machines. This field observation was supported by the opinion of the majority of the Kittilä mine workers. However, some remaining concerns must be addressed before BEVs can replace diesel machines. Validerad;2022;Nivå 2;2022-03-15 (hanlid) Sustainable Intelligent Mining Systems (SIMS)

Introduction Patients with midgut neuroendocrine tumours (NETs) suffer from decreased health-related quality of life (HRQoL), in large part due to bowel symptoms. However, it is unknown which bowel symptoms affect HRQoL the most. An enhanced understanding of this is essential to better focus treatment on this aspect of the disease. This study aimed to determine which bowel symptoms affect HRQoL the most in patients with midgut NETs. Methods Consenting patients with midgut NET completed the Memorial Sloan Kettering Bowel Function Instrument and the HRQoL questionnaire (EORTC QLQ-C30). The correlation between bowel symptoms and HRQoL was analysed using multiple linear regression, adjusting for age, Charlson Comorbidity Index score, presence of metastatic disease, chromogranin A, and BMI yielding ß-coefficients with 95% confidence intervals. Results Totally, 119 patients with midgut NET completed the questionnaires and were included in the study. Loose stool and bowel frequency ≥ 3/day were the most common bowel symptoms, reported by 47% and 56% of patients, respectively. However, sensitivity to certain types of food and beverages, a feeling of incomplete emptying of the bowel, and soiling were the symptoms most strongly correlated with decreased HRQoL, especially within domains concerning role and social function, with ß-coefficients for the strongest correlated symptoms of 15.0 and 14.6, respectively. Discussion While symptoms concerning stool consistency and frequency are common in patients with midgut NET, our study suggests that other, more socially stigmatising symptoms affect patients’ HRQoL more. Our findings could help caregivers understand patients’ perceptions of the disease and provide avenues for more directed therapies.

AIM Visceral obesity is associated with perioperative and postoperative complications in colorectal surgery. We aimed to investigate the association between the perirenal fat surface area (PRF) and postoperative complications. METHOD Data on 610 patients undergoing curative, elective colon cancer resection between 2006 and 2016 at Stockholm South General Hospital were retrieved from a local quality register. We assessed perioperative and postoperative outcomes using a multinomial regression model adjusted for age, sex, American Society of Anesthesiologists classification and surgical approach (open/laparoscopy) in relation to PRF. RESULTS PRF could be measured in 605 patients; the median area was 24 cm2 . Patients with PRF ≥ 40 cm2 had longer operation time (median 223 vs 184 min), more intra-operative bleeding (250 vs 125 ml), reoperations (11% vs 6%), surgical complications (27% vs 13%) and nonsurgical infectious complications (16% vs 9%) than patients with PRF < 40 cm2 , but there were no differences in the need for intensive care or duration of hospital stay. The multivariate analyses revealed an increased risk of any complication [OR 1.68 (95% CI 1.1-2.6)], which was even more pronounced for moderate complications [Clavien-Dindo II, OR 2.14 (CI 1.2-2.4]; Clavien-Dindo III, OR 2.35 (CI 1.0-5.5)] in patients with PRF ≥ 40 vs < 40 cm2 . The absolute risk of complications was similar in men and women with PRF ≥ 40 cm2 . CONCLUSION PRF, an easily measured indirect marker of visceral obesity, was associated with overall and moderate complications in men and women and could serve as a useful tool in the assessment of preoperative risk.

A full-thickness biopsy of the bowel wall is required to evaluate the enteric nervous system. A patient with aggravating gastrointestinal symptoms underwent a laparoscopic full-thickness biopsy of the ileum and, 1 year later, an endoscopic full-thickness biopsy of the sigmoid colon. Both samples showed enteric neuropathy characterized by vacuolated and enlarged neurons. The length of the myenteric plexus was greater in the endoscopic (23 mm) compared to the laparoscopic (11 mm) biopsy, with fewer tissue artefacts in the laparoscopic approach. Clinical deterioration was paralleled by enteric neuropathy with an increase in the percentage of vacuolated and enlarged enteric neurons from 24 to 35%.

Background The role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment. Method Patients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10 years were included at 21 emergency surgical centres and from age 5 years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score-based algorithm was implemented during the intervention period. Intermediate-risk patients were randomized to routine imaging or selective imaging after clinical reassessment. Results The baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate-risk patients were randomized. In low-risk patients, use of the AIR score-based algorithm resulted in less imaging (19·2 versus 34·5 per cent; P < 0·001), fewer admissions (29·5 versus 42·8 per cent; P < 0·001), and fewer negative explorations (1·6 versus 3·2 per cent; P = 0·030) and operations for non-perforated appendicitis (6·8 versus 9·7 per cent; P = 0·034). Intermediate-risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (6·4 versus 6·7 per cent respectively; P = 0·884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (53·4 versus 46·3 per cent; P = 0·020). Conclusion AIR score-based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 (http://www.clinicaltrials.gov).

Summary In Sweden the use of geophysical investigation methods as complement to geotechnical investigations in larger infrastructure projects have increased during the last 10 years. One of the main reason’s is probably the increasing use of planning tools in 3D, which increases the need for better data coverage. However, geophysics is still not counted as a standard method in the toolbox for ground investigations and the amount of geophysical investigations carried out in Swedish infrastructure projects differ a lot, due to several reasons. This abstract will discuss how and why geophysical investigations become or not become a part of larger infrastructural projects in Sweden and also discuss what should be done in the future to promote the use of geophysical investigation techniques. The main points of actions concerns purpose and expectations, awareness, uncertainty, standards and tools.

Gastrointestinal complaints without obvious organic causes confirmed by clinical laboratory analyses, endoscopy or radiology are often referred to functional entities. Irritable bowel syndrome (IBS) is the most common functional disorder in the gut. Careful examination of these patients may reveal other diagnoses of defined etiologies, e.g., enteric neuropathy, microscopic colitis, and primary Sjögre’s syndrome. The present case describes a young patient with incapacitating gastrointestinal symptoms presumed to be IBS, who underwent endoscopic full-thickness biopsy in sigmoid colon. Histopathological examination revealed degenerative enteric neuropathy, possibly secondary to chronic ischemia.

Background Sjogren9s syndrome occurs in isolation (primary Sjogren9s syndrome, pSS), but it is also often secondary (sSS) to, and sometimes difficult to delineate from, other rheumatic diseases, in particular from systemic lupus erythematosus (SLE). Consequently there is a need to investigate similarities and differences between SLE patients with (SLE-sSS) and without sSS (SLE-noSS). Objectives To investigate the occurrence of sSS in a large cohort of SLE patients and to explore clinical and laboratory characteristics associated with SLE-sSS as compared to SLE-noSS and controls. Methods We included 504 consecutive SLE patients and 322 population controls, individually matched for age and gender to the first patients. All patients fulfilled the 1982 revised ACR criteria for SLE. SLE-sSS was defined according to the American-European consensus criteria (AECC). Accordingly, subjective and objective quantifications of sicca symptoms were recorded on all subjects. All underwent a thorough clinical investigation. SLE-associated autoantibodies, (ANA screening by BioPlex 2200 system, Bio-Rad) and Rheumatoid factor (RF, Phadia Immunocap 250) were determined with standardized methods for all subjects, Routine laboratory workup and a panel of cytokines (MSD 30-plex cytokine assays, performed on samples from 433 consecutive SLE patients and 319 controls) were measured on fasting blood samples. Results SLE-sSS, as defined by AECC, occurred in 23% of the SLE patients. Compared to SLE-noSS the SLE-sSS group was older, both at inclusion (55 vs 43yrs, p Conclusions Through strictly applying the AECC criteria we report that the frequency of SLE-sSS increases with age and affects roughly ¼ of SLE patients. Nephritis was less common while leucopenia and peripheral neuropathy were more common among SLE-sSS patients. In addition to excess of well-known SS-associated autoantibodies we report higher levels of six pro-inflammatory cytokines in SLE-sSS as compared to SLE-noSS. These findings demonstrate that, though often regarded as a milder version of SLE, patients with SLE-sSS are characterized by a state of chronic systemic inflammation. Acknowledgements Susanna Eketjall at Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Integrated Cardio Metabolic Centre (ICMC), Karolinska Institutet, Huddinge, Sweden Disclosure of Interest None declared

Background and aims Interferon (IFN)-αs are pivotal in systemic lupus erythematosus (SLE), and type III IFNs (IFN-λs) were recently also associated with SLE. We investigated levels of IFN-α and IFN-λ1, and related cytokines in SLE patients and controls. Methods We included 261 SLE patients and 261 population controls. All were examined and assessed for current organ manifestations and disease activity/damage using SLAM, SLEDAI and ACR/SDI scales. Levels of IFN-λ1, IFN-α, IL-17A, IL-23 and IP-10 were measured by ELISA. Results IFN-λ1 and IFN-α were detected in 29% and 44% of patients respectively, but their levels did not correlate. High serum levels of IFN-λ1 were positively associated with anti-nucleosome antibodies and lymphopenia, but negatively with musculoskeletal damage. Positive correlations between levels of IFN-λ1, IL-17A and IL-23 were observed. Patients with high levels of these three cytokines had more disease damage, especially renal. High levels of IFN-α were associated with mucocutaneous disease, leukopenia, low complement, Ro/SSA and La/SSB, whereas vascular events and antiphospholipid antibodies (aPL) were uncommon. We identified two subgroups with high disease activity: one double IFN-λ1 and IFN-α high and another IP-10 high. The former had more neuropsychiatric manifestations, while the latter had more arthritis. Conclusions Measurements of circulating IFN-λ1 and IFN-α define SLE patients with different characteristics. Levels of IFN-λ1 correlate with Th17 cytokines and identify a subgroup with more damage. Disease activity is associated with either upregulation of both type I and III IFNs, or independently with IP-10. Our findings could be of major importance when tailoring therapy for SLE patients with agents targeting IFN-pathways.

Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects patients with a loss of speech and mobility. The aim of this study was to describe patients’ experiences of living with ALS in the end-of-life situations. A manifest content analysis was chosen for analysis narratives from four biographies by women who had ALS. The categories Suffering, Meaningfulness, and Experiences of a Limited life were identified as describing patients’ understanding of living with ALS. Nurses need to be trained in communication skills to maintain human dignity for patients who lost their speech regarding an intellect in shape. There is a need for information among family members about severe diseases, such as ALS, to improve high quality of care and well-being for all involved. Home health care has to invite and facilitate patients’ and relatives’ participation regarding the end-of-care processes to improve a sense of coherence to handle everyday life situation in the future.

BACKGROUND AND AIMS. Microscopic colitis (MC), predominantly affecting women, is associated with thyroid disorders, although purely defined of which type, or compared with controls. Its association with subclinical thyroid disorders, and related increased risk of cardiovascular diseases, has never been examined. The aim was to examine the prevalence of autoantibodies and subclinical and clinical thyroid dysfunction in female patients with MC compared with controls. METHODS. Women younger than 73 years old with biopsy-verified MC from the Department of Gastroenterology in Skåne, during 2002-2010, were invited. Out of 240 identified, 133 were finally included. A questionnaire about medical history was completed and blood samples were collected. Serum was analyzed for free thyroxin and triiodothyronine, thyroid-stimulating hormone and anti-thyroid peroxidase (anti-TPO) antibodies. A population-based group of 737 women served as controls. RESULT. The prevalence of thyroid disorders in patients was higher compared to controls [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.78-4.99], but the prevalence of subclinical disorders was not different (OR = 1.18, 95% CI = 0.48-2.85). Anti-TPO antibodies were present in 10.6% of MC patients and 18.6% of controls. Twenty-five MC patients had hypothyroidism: 15 with Hashimoto's hypothyroidism, 6 with completed treatment of thyrotoxicosis and 4 with completed surgery after nontoxic goiter. CONCLUSION. Thyroid disorders, autoimmune hypothyroidism being most frequent, are more prevalent in patients with MC than in controls, whereas the prevalence of subclinical thyroid disorders in MC patients does not differ significantly from controls.

Personal Rapid Transit (PRT) is a transportation concept with small vehicles on a low weight structure, that combines many of the best aspects of today's urban public transport, and packages them together with unparalleled service and lower total cost of ownership. Vectus, with operations in Korea and Sweden, is at the forefront of PRT technology. Vectus has built a PRT test track in Sweden for validation of the system, and for obtaining safety approval. For the test track, in-track linear motors are used powered by standard industry inverters combined with an in-house control concept. The system and its operational experiences are described.

Background and Purpose. Many women suffer from back pain and experience activity limitation post-partum. To our knowledge the physiological factors and physiotherapy related to back pain post-partum have received limited evaluation and the effectiveness of specific physiotherapeutic approaches to exercise should be tested. In addition, there has been limited research on kinesiophobia in women with back pain post-partum. The purpose of the current study was to test the influence of specific trunk muscle training on pain, activity limitation and kinesiophobia in 10 subjects with back pain post-partum. Method. The treatment consisted of specific deep muscle training of the transversus abdominus and multifidus muscles. Pain was rated based on the visual analogue scale (VAS) and pain drawings. Activity limitation was recorded using the Disability Rating Index. Kinesiophobia was evaluated using the Swedish version of the Tampa Scale for Kinesiophobia. An A–B–A single-subject research design was used and a number of measurements were obtained during each phase. The analysis consisted of a visual inspection and a two standard deviation band test (2-SD). Results. The visual analysis showed a trend towards reduced pain and activity limitation for all 10 subjects. The 2-SD test showed mixed results among all subjects. In addition, all subjects reported kinesiophobia before and after treatment. Conclusions. Individual specific deep muscle training of the transversus abdominus and multifidus muscles reduced pain and activity limitation in women with back pain post-partum. Further research is needed to determine more precisely how kinesiophobia affects women with back pain post-partum. Copyright © 2007 John Wiley & Sons, Ltd.

The 51 human adenovirus serotypes are divided into six species (A to F). Adenovirus serotypes from all species except species B utilize the coxsackie-adenovirus receptor for attachment to host cells in vitro. Species B adenoviruses primarily cause ocular and respiratory tract infections, but certain serotypes are also associated with renal disease. We have previously demonstrated that adenovirus type 11 (species B) uses CD46 (membrane cofactor protein) as a cellular receptor instead of the coxsackie-adenovirus receptor (A. Segerman et al., J. Virol.77:9183-9191, 2003). In the present study, we found that transfection with human CD46 cDNA rendered poorly permissive Chinese hamster ovary cells more permissive to infection by all species B adenovirus serotypes except adenovirus types 3 and 7. Moreover, rabbit antiserum against human CD46 blocked or efficiently inhibited all species B serotypes except adenovirus types 3 and 7 from infecting human A549 cells. We also sequenced the gene encoding the fiber protein of adenovirus type 50 (species B) and compared it with the corresponding amino acid sequences from selected serotypes, including all other serotypes of species B. From the results obtained, we conclude that CD46 is a major cellular receptor on A549 cells for all species B adenoviruses except types 3 and 7.

By transmitting some sound through the earshell, an active-sound transmission ear protector is more comfortable than a passive design. The authors explain how careful attention to sound control can improve comfort levels further.

Background Microscopic colitis (MC) induces gastrointestinal symptoms, which are partly overlapping with irritable bowel syndrome (IBS), predominately in middle-aged and elderly women. The etiology is unknown, but association with smoking has been found. The aim of this study was to examine whether the increased risk for smokers to develop MC is a true association, or rather the result of confounding factors. Therefore, patients suffering from MC and population-based controls from the same geographic area were studied regarding smoking- and alcohol habits, and other simultaneous, lifestyle factors, concerning the clinical expression of the disease. Methods Women at the age of 73 years or younger, who had been treated for biopsy-verified MC at any of the Departments of Gastroenterology in Skåne, between 2002 and 2010, were invited to the study (240 patients). Women (737) from the population-based prospective cohort study, Malmö Diet and Cancer Study (MDCS), served as controls. A self-administered questionnaire about lifestyle factors, gastrointestinal symptoms, medical conditions and medication at the time for the study was sent by post. Results Altogether, 131 women with MC could be included after age-matching with controls (median age 56 years) and exclusion of secondary MC. Patients were divided into persistent MC (MC1) and transient MC (MC2). Past smoking was associated with increased risk to develop MC2 (OR = 2.67, 95 CI = 1.15–6.23), whereas current smoking was associated with increased risk to develop MC1 (OR = 3.18, 95 CI = 1.57–6.42). Concomitant symptoms of IBS were associated with smoking (OR = 4.24, 95 CI = 1.92–9.32). Alcohol drinking had no association with MC or IBS. Conclusions The results suggest that past smoking is associated with transient MC, whereas current smoking is associated with persistent MC. Smoking is associated with MC patients with concomitant IBS-like symptoms.

Ion beam analysis methods generally rely on either the scattering of a high energy primary particle, or secondary process arising from the stopping of this particle in the substrate. The information typically obtained is the identification and quantitation of elements present, often resolved in terms of their depth distribution. However, there are a variety of techniques which offer complementary information on the structure composition and chemistry of a surface. These are typified by rather softer interactions with the surface, typified by low energy (kV) ion beams or photons, which interact with the surface in rather more complex manner than higher energy ion beams. The combination of energy and momentum transfer for the ion beams, makes these methods less quantitative, but opens up the potential for more chemically detailed information on the nature of the surface. Secondary ion mass spectrometry (SIMS), both static and dynamic, and X-ray Photoelectron Spectroscopy (XPS) will be discussed in some detail. SIMS offers excellent compositional depth profiling capability, but offers poor quantitation, while XPS offers unparalleled chemical detail, but limited lateral and depth resolution. The underlying processes which dictate the strengths and limitations of these techniques are discussed, along with a number of typical applications to the analysis of oxide films and polymeric materials.

Diabetes control deteriorates in girls at cessation of growth: relationship with body mass index.

Porous silicon layers with thicknesses in the range 100-400 nm and average porosities in the range 38-71% were prepared by electrochemical anodization. Variable angle spectroscopic ellipsometry was ...

The aggregates formed by sonication of mixtures of triacylglycerols (triglycerides) (TG) and egg phosphatidylcholine (EPC) have been examined at 25°C at 6 [TG]/[EPC] ratios ranging from 0 to ≈1 (mol/mol) by gel exclusion chromatography and quasi-elastic light scattering. The solubilization by Triton X-100 of the aggregates formed has been followed at 25°C for different lipid concentrations at each of the 6 [TG]/[EPC] ratios by continuous turbidity monitoring and quasi-elastic light scattering. Analysis of the four steps, separated by three break points, observed on turbidity curves during the partial solubilization of mixed aggregates indicated the formation of two types of aggregates, vesicles and emulsion particles. These structures were confirmed by cryotransmission electron microscopy. The solubility limit of TG in phosphatidylcholine vesicles was found to be about 3.8 mol%.

This paper demonstrates modeling of the busbars and the magnetic field in an aluminum reduction cell. The methodology presented is focused on a series of fast and effective numerical calculations, where in the initial state the busbars of the reduction cell are represented by an equivalent resistance network. The analysis relies on calculating a complete finite element model with different wave forms imposed on the liquid fluid interface for magnetohydrodynamic stability calculation purposes. Principles of the approach are presented and results from a reduction cell analysis are shown

The comparison of the antibiotic activity of isovelleral (1) and the two synthetic compounds 3 and 4 with data from molecular mechanics calculations, suggest that the reaction of isovelleral with amines to form pyrrole derivatives, as previously has been observed with the dialdehyde polygodial (2), may be responsible for its bioactivities. Isovelleral (1) was found to react with 1,3-diaminopropane in ethanol, and a pyrrole derivative was isolated and characterised. However, the reaction was slow and several other products were also formed, and polygodial (2), which is as antibiotic as 1, reacts more than 100 times faster with propylamine and lysine. It is therefore unlikely that the reaction with primary amines to form pyrrole derivatives is responsible for the antibiotic activity of isovelleral (1).

We have reported that transmembrane mucin MUC17 binds PDZ protein PDZK1, which retains MUC17 apically in enterocytes. MUC17 and transmembrane mucins MUC3 and MUC12 are suggested to build the enterocyte apical glycocalyx. Carbachol (CCh) stimulation of the small intestine results in gel-forming mucin secretion from goblet cells, something that requires adjacent enterocytes to secrete chloride and bicarbonate for proper mucin formation. Surface labeling and confocal imaging demonstrated that apically expressed MUC17 in Caco-2 cells and Muc3(17) in murine enterocytes were endocytosed upon stimulation with CCh. Relocation of MUC17 in response to CCh was specific as MUC3 and MUC12 did not relocate following CCh stimulation. MUC17 colocalized with PDZK1 under basal conditions, while MUC17 relocated to the terminal web and into early endosomes after CCh stimulation. CCh stimulation concomitantly internalized the Na+/H+exchanger 3 (NHE3) and recruited cystic fibrosis transmembrane conductance regulator (CFTR) to the apical membranes, a process that was important for CFTR-mediated bicarbonate secretion necessary for proper gel-forming mucin unfolding. The reason for the specific internalization of MUC17 is not understood, but it could limit the diffusion barrier for ion secretion caused by the apical enterocyte glycocalyx or alternatively act to sample luminal bacteria. Our results reveal well-orchestrated mucus secretion and trafficking of ion channels and the MUC17 mucin.

The association between low birth weight and adult disease is well known. Less is known on long-term effects of high birth weight.This study aims to investigate whether a high birth weight increases risk for adult metabolic disease.Swedish term single births, 1973-1982 (n = 759,999), were studied to age 27.5-37.5 years using Swedish national registers. Hazard ratios (HRs) were calculated in relation to birth weight for type 2 diabetes, obesity, hypertension and dyslipidaemia.Men with birth weights between 2 and 3 standard deviation score (SDS) had a 1.9-fold increased risk (HR 1.91, 95% confidence interval [CI] 1.25-2.90) of type 2 diabetes, whereas those with birth weights above 3 SDS had a 5.4-fold increased risk (HR 5.44, 95% CI 2.70-10.96) compared to men with birth weights between -2 and 2 SDS. The corresponding HRs for women were 0.60 (95% CI 0.40-0.91) and 1.71 (95% CI 0.85-3.43) for birth weights 2-3 SDS and3 SDS, respectively. Men with birth weights between 2 and 3 SDS had a 1.5-fold increased risk (HR 1.47, 95% CI 1.22-1.77) of obesity. The corresponding risk for women was 1.3-fold increased (HR 1.32, 95% CI 1.19-1.46). For men and women with birth weights above 3 SDS, the risks of adult obesity were higher, HR 2.46 (95% CI 1.63-3.71) and HR 1.85 (95% CI 1.44-2.37), respectively.A high birth weight, particularly very high, increases the risk of type 2 diabetes in male young adults. The risk of obesity increases with increasing birth weight in both genders.

The Ro52 protein of the Ro/SSA antigen was recently defined as an E3 ligase controlling cytokine production. Autoantibodies from systemic lupus erythematosus (SLE) patients targeting the Ro52-RING domain, containing the E3 ligase activity, have been shown to inhibit the E3 ligase activity of Ro52. The objective of the present study was to investigate correlations between clinical parameters in patients with SLE and levels of Ro/SSA (Ro52 and Ro60) and La/SSB autoantibodies, including autoantibodies directed towards the functional RING and B-box domains of the Ro52 protein. SLE patients ( n = 232) were clinically examined and disease activity indices collected concurrently to blood sampling. The samples were analyzed for immunological parameters including autoantibodies. Ro52 autoantibody levels were associated with more variables than the other analyzed antibodies and were significantly associated with several individual items related to sSS and the diagnosis of sSS itself ( p = 0.004). Other associated variables were high sedimentation rate ( p = 0.0003), levels of immunoglobulins ( p = 0.0003), and an inverse correlation with levels of lymphocytes ( p = 0.003) and leukocytes ( p = 0.01). Antibodies to the RING domain of Ro52, which is the functionally active domain with E3 ligase activity, were significantly correlated with disease activity as measured by the SLAM score. We conclude that autoantibodies against Ro52 and in particular its functional RING domain are important in lupus patients and associated with several clinical and laboratory features of the disease. The impact on disease activity of Ro52-RING specific antibodies was especially noted, and could imply a functional role for these autoantibodies in inhibiting Ro52 activity, which is important for the control of proinflammatory cytokine production, including type 1 interferons.

Overweight and obesity are risk factors for cardiovascular disease. There is also an association between body mass index (BMI) and cognitive ability. Since low birth weight is associated with adult metabolic disease, particularly in obese subjects, the question emerges whether obesity has an additional negative effect on cognitive function in subjects with low birth weight.The aim was to analyse whether overweight or obesity influence intellectual performance in young adults with particular focus on those with a low birth weight.Data were collected from the Swedish Medical Birth Register on 620,834 males born between 1973 and 1988 and matched to results on intellectual performance and BMI at conscription.The risk for low intellectual performance was higher for those with high BMI compared to those with normal. The highest risk was found among subjects with low birth weight and overweight or obesity in young adulthood (odds ratios, 1.98 [1.73-2.22] and 2.59 [2.00-3.34], respectively). However, subjects with further high birth weight and a high BMI at conscription had no further increased risk.Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance. A high birth weight increases the risk for obesity, but a high adult BMI does not further increase the risk for subnormal performance.

Background Type I interferons (IFN), particularly IFN-αs, are considered to have a pivotal role in SLE. Recently, increased levels of type III IFNs (IFN-λs) have been described to be also associated with SLE. Objectives We measured circulating levels of IFN-λ, IL-17, IL-23, IP-10 and also IFN-α, in a cohort of SLE patients and investigated their association with clinical and laboratory manifestations of the disease. Population controls were investigated as comparators. Methods 261 SLE patients and 276 population controls, identified through the population registry and matched for age, sex, and region of living, were included. All participants were examined by clinician rheumatologist and assessed for current organ manifestations and disease related organ damage. Sera were collected at inclusion and stored at -70* C until analysis. Serum levels of IFN-α, IFN- λ, IL-17, IL-23 and IP-10 were measured in sera by commercial ELISA. Results IFN-λ was detected in 76 (29,1%) patients and IFN-α in 115 (44%). In 108 patients (41.4%) neither of the cytokines was detected. Both IFN-λ and IFN-α were detected more often and in higher levels in patients. IFN-λ levels did not correlate to the levels of IFN-α, and only in 38 (14.5%) patients had detectable levels of both. Levels of IL-17, IL-23 and IP-10 correlated with each other and with IFN-λ. In comparison, only a weak correlation between levels of IFN-α and IL-23 was observed. Detectable levels of IFN-λ were associated with lower incidence of fever, photosensitivity and also arthritis. Patients with detectable IFN-α had active mucocutaneous disease, serositis and lower levels of C3 and C4, and also presence of anti-Ro/SSA and anti-La/SSB. Incidence of nefritis and DVT was lower in this group. Co-detection of IFN-α and IFN-λ was significantly associated with lymphadenopathy, serositis, cortical dysfunction and presence of antiphospolipid antibodies. IFN-α was associated with overall lower disease damage. However, IFN-λ was associated with lower incidence of musculoskeletal, but higher frequency of cerebrovascular damage. The triple detection of IFN-λ, IL-17 and IL-23 was significantly associated with overall higher disease damage score, and particularly higher incidence of renal damage. Conclusions Our study demonstrates that in SLE patients the levels of IFN-α and IFN-λ do not correlate, but rather dissect patient9s groups with different target organs. Triple positivity for IFN-λ, IL-17 and IL-23 is associated with the higher disease damage, in particular kidney damage. References Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity. Wu Q, Yang Q, Lourenco E, Sun H, Zhang Y. Arthritis Res Ther. 2011 Jun 16. Disclosure of Interest None declared

Background There is presently no consensus on how to best measure disease activity in systemic lupus erythematosus (SLE). Available validated measures, such as SLE Disease Activity Index (SLEDAI) and SLE Activity Measure (SLAM), are composite scores that in addition to laboratory tests require investigation by a physician. These scores are insensitive to change and have failed to differentiate treatment responses in clinical trials. It would be an important step forward, for clinical practice and for clinical trials, if one or several biomarkers could be used as proxies for disease activity in SLE. Objectives Our objective is to evaluate cytokines, in combination with basic laboratory tests, as potential disease activity biomarkers. Methods In a cross-sectional setting we examined 433 patients with SLE (fulfilling four or more of the 1982 revised ACR criteria) and 322 age and gender matched population controls. Disease activity was assessed according to both SLEDAI and SLAM by a rheumatologist. Basic laboratory tests and analyses on MSD 30-plex cytokine assay (Mesoscale Discovery, K15054D) were performed on fasting blood samples (total >50 potential biomarkers). The discriminatory power for investigated biomarkers was tested between patients and controls. Spearman correlations with SLAM/SLEDAI scores were calculated among patients. Results Many potential biomarkers discriminated between patients and controls. Best discriminatory power was observed for TNF-α (p=7x10 –63 ), IL-6 (p=2.5x10 –40 ), orosomucoid (p=7.1x10 –38 ), plasma (P)-albumin (p=1.6x10 –36 ) and sedimentation rate (SR) (p=5.6x10 –34 ). The strongest correlations with SLEDAI/SLAM were observed for TNF-α (Spearman ρ=0.32, p=6.0x10 –12 for SLEDAI and Spearman ρ=0.34, p=5.0x10 –13 for SLAM), and for P-albumin (Spearman ρ=-0.33, p=9.0x10 –13 for SLEDAI and Spearman ρ=-0.31, p=5.0x10 –11 for SLAM). As SR is part of SLAM, expected positive correlations were observed (Spearman ρ=0.27, p=7.7x10 -9 for SLEDAI and Spearman ρ=0.48, p=4.0x10 –25 for SLAM). Conclusions Of more than 50 investigated biomarkers TNF-α was the best discriminator between SLE patients and controls. Furthermore TNF-α was the biomarker, which correlated best with disease activity. These correlations were further improved by the ratio between TNF-α and P-albumin. We propose that the TNF-α/P-albumin ratio merits further investigations as a clinically useful biomarker for diagnostic and surveillance purposes in SLE. Disclosure of Interest None declared

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.