No evidence for fixation of mesh in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the differences in hernia recurrence and chronic postoperative inguinal pain (CPIP) in randomized, controlled trials comparing fixation and non-fixation of the mesh in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair. METHODS: A multi-database systematic search was conducted for randomized, controlled trials comparing fixation versus non-fixation of the mesh in TAPP inguinal hernia repair. All eligible papers were assessed for risk of bias using the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Quality of evidence was evaluated using the GRADE system. Meta-analyses were performed regarding recurrence and CPIP using RevMan. RESULTS: Seven prospective, randomized controlled trials were included. Laparoscopic TAPP inguinal hernia repair was performed in 1732 patients with 737 procedures performed without fixation and 995 procedures with fixation of the mesh. Despite all trials being RCTs, the trials were limited by substantial bias and the quality of evidence was low regarding hernia recurrence and very low regarding CPIP. Pooled estimates from meta-analyses were an OR of 2.80 (95% CI 0.61-12.77) for hernia recurrence and a mean difference in visual analogue scale (VAS) of 0.17 (95% CI 0.90-1.24) for CPIP, respectively. CONCLUSION: The current evidence is very uncertain and mesh fixation may have little to no effect regarding hernia recurrence and chronic postoperative inguinal pain in patients operated with TAPP inguinal hernia repair.

Initial Diagnosis of ALK-Positive Non-Small-Cell Lung Cancer Based on Analysis of ALK Status Utilizing Droplet Digital PCR.

We describe a novel droplet digital PCR (ddPCR) assay capable of detecting genomic alterations associated with inversion translocations. It is applied here to detection of rearrangements in the anaplastic lymphoma kinase (ALK) gene associated with ALK-positive non-small-cell lung cancer (NSCLC). NSCLC patients may carry a nonreciprocal translocation on human chromosome 2, in which synchronized double stranded breaks (DSB) within the echinoderm microtubule-associated protein-like 4 (EML4) gene and ALK lead to an inversion of genetic material that forms the non-natural gene fusion EML4-ALK encoding a constitutively active tyrosine kinase that is associated with 3 to 7% of all NSCLCs. Detection of ALK rearrangements is currently achieved in clinics through direct visualization via a fluorescent in situ hybridization (FISH) assay, which can detect those rearrangements to a limit of detection (LOD) of ca. 15%. We show that the ddPCR assay presented here provides a LOD of 0.25% at lower cost and with faster turnaround times.

Characterizing the concept of activity pacing as a non-pharmacological intervention in rheumatology care: results of an international Delphi survey.

OBJECTIVE: To develop a consensual list of the most important aspects of activity pacing (AP) as an intervention within the context of non-pharmacological rheumatology care. METHOD: An international, multidisciplinary expert panel comprising 60 clinicians and/or healthcare providers experienced in AP across 12 different countries participated in a Delphi survey. Over four Delphi rounds, the panel identified and ranked the most important goals of AP, behaviours of AP (the actions people take to meet the goal of AP), strategies to change behaviour in AP, and contextual factors that should be acknowledged when instructing AP. Additionally, topics for future research on AP were formulated and prioritized. RESULTS: The Delphi panel prioritized 9 goals, 11 behaviours, 9 strategies to change behaviour, and 10 contextual factors of AP. These items were integrated into a consensual list containing the most important aspects of AP interventions in non-pharmacological rheumatology care. Nine topics for future research on AP with the highest ranking were included in a research agenda highlighting that future research should focus on the effectiveness of AP interventions and on appropriate outcome measures to assess its effectiveness, as selected by 64% and 82% of the panellists, respectively. CONCLUSIONS: The diversity and number of items included in the consensual list developed in the current study reflect the heterogeneity of the concept of AP. This study is an important first step in achieving more transparency and homogeneity in the concept of AP in both rheumatology daily clinical practice and research.

Metabolic syndrome in first-time hospitalized patients with depression: a 1-year follow-up study.

OBJECTIVE: Studies on metabolic syndrome (MetS) in younger patients with depression are few. We examined the prevalence and progression of MetS in first-time hospitalized patients with depression during 1 year of follow-up. Furthermore, we explored putative risk factors of MetS. METHOD: We evaluated MetS and its components in first-time hospitalized patients with depression (N = 52) and healthy controls (N = 50) (18-45 years). Physical activity, aerobic fitness, sleeping disturbances, smoking and dietary habits, and psychopharmacological treatment were recorded at baseline for all participants and after 1 year for the patients. RESULTS: Patients had significantly higher waist circumference (WC) and lower high-density lipoproteins compared with healthy controls (P < 0.05). Patients had higher prevalence of MetS, but this was not significant when adjusted for age. Patients had significant increase in WC and triglycerides and a non-significant increase in the prevalence of MetS. Antipsychotic medication (OR 10.5, 95% CI 1.18-94.14) and low aerobic fitness (OR 0.79, 95% CI 0.68-0.93) were significantly correlated with MetS (P < 0.05). CONCLUSION: Metabolic syndrome is highly prevalent in younger, severely depressed patients and the incidence increases during 1 year of follow-up. Low aerobic fitness and use of atypical antipsychotics are strongly correlated with MetS.

Self-reported quality care for knee osteoarthritis: comparisons across Denmark, Norway, Portugal and the UK.

OBJECTIVES: To assess and compare patient perceived quality of osteoarthritis (OA) management in primary healthcare in Denmark, Norway, Portugal and the UK. METHODS: Participants consulting with clinical signs and symptoms of knee OA were identified in 30 general practices and invited to complete a cross-sectional survey including quality indicators (QI) for OA care. A QI was considered as eligible if the participant had checked 'Yes' or 'No', and as achieved if the participant had checked 'Yes' to the indicator. The median percentage (with IQR and range) of eligible QIs achieved by country was determined and compared in negative binominal regression analysis. Achievement of individual QIs by country was determined and compared using logistic regression analyses. RESULTS: A total of 354 participants self-reported QI achievement. The median percentage of eligible QIs achieved (checked 'Yes') was 48% (IQR 28%, 64%; range 0-100%) for the total sample with relatively similar medians across three of four countries. Achievement rates on individual QIs showed a large variation ranging from 11% (referral to services for losing weight) to 67% (information about the importance of exercise) with significant differences in achievement rates between the countries. CONCLUSIONS: The results indicated a potential for improvement in OA care in all four countries, but for somewhat different aspects of OA care. By exploring these differences and comparing healthcare services, ideas may be generated on how the quality might be improved across nations. Larger studies are needed to confirm and further explore the findings.

Metabolic syndrome and aerobic fitness in patients with first-episode schizophrenia, including a 1-year follow-up.

OBJECTIVE: To compare the prevalence of metabolic syndrome (MetS) and metabolic abnormalities in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls; to investigate changes in MetS during 1year of treatment; and to investigate predictors of MetS. METHODS: Patients with FES (N=99) and healthy controls (N=50) were included in the study. MetS was defined according to IDF based on waist circumference (WC), blood pressure (BP), triglycerides (TG), high-density lipoprotein (HDL), and fasting-glucose. Data on physical activity, aerobic fitness, smoking, and dietary habits, sleeping disturbances, psychopathology and psychotropic medication were also obtained. Patients were assessed at baseline and at 1year follow-up. RESULTS: Compared with healthy controls patients with FES had a higher baseline prevalence of MetS (p=.07), and metabolic abnormalities: WC (p<.01), TG (p<.01), HDL (p=.017), and fasting glucose (p=.04). Patients with FES had significantly increased prevalence of MetS (p=.03), WC (p=.04), and TG (p=.01) during the study period. Antipsychotics and low physical activity were significantly correlated with the increase in metabolic abnormalities. In multivariate analyses low aerobic fitness was the most consistent and significant predictor of metabolic abnormalities and MetS. CONCLUSION: MetS and metabolic abnormalities are highly prevalent in patients with FES, and both increase significantly during 1year of treatment. Apart from confirming the metabolic adverse effects of antipsychotics, our study highlights that low aerobic fitness is a significant risk factor for MetS. Promoting a healthier lifestyle should be part of psychiatric treatment and rehabilitation.

The Effect of Performing Bi- and Unilateral Row Exercises on Core Muscle Activation.

The purpose of the study was to compare core muscle activation in 3 different row exercises (free-weight bent-over row, seated cable row and machine row) performed unilaterally and bilaterally, at matched effort levels. 15 resistance-trained men (26.0±4.4 years, 81.0±9.5 kg, 1.81±0.07 m) performed the exercises in randomized order. For erector spinae and multifidus, EMG activities in unilateral machine- and cable row were 60-63% and 74-78% of the bilateral performance (P≤0.036). For external oblique, the EMG activities recorded during bilateral exercises were 37-41% of the unilateral performance (P≤0.010). In unilateral cable- and machine rows, the EMG activities in external oblique and multifidus were 50-57% and 70-73% of the free-weight row (P≤0.002). In bilateral free-weight row, EMG activity in erector spinae was greater than bilateral machine- (+34%, P=0.004) and unilateral free-weight rows (+12%, P=0.016). For rectus abdominis there were no significant differences between conditions. In conclusion, 1) free-weight row provided greater EMG activity in erector spinae (bilaterally and unilaterally) and multifidus (unilaterally) than machine row; 2) unilateral performance of exercises activated the external oblique more than bilateral performance, regardless of exercise; and 3) generally bilateral performance of exercises provided higher erector spinae and multifidus EMG activity compared to unilateral performance.

A new general model for predicting melting thermodynamics of complementary and mismatched B-form duplexes containing locked nucleic acids: application to probe design for digital PCR detection of somatic mutations.

Advances in real-time polymerase chain reaction (PCR), as well as the emergence of digital PCR (dPCR) and useful modified nucleotide chemistries, including locked nucleic acids (LNAs), have created the potential to improve and expand clinical applications of PCR through their ability to better quantify and differentiate amplification products, but fully realizing this potential will require robust methods for designing dual-labeled hydrolysis probes and predicting their hybridization thermodynamics as a function of their sequence, chemistry, and template complementarity. We present here a nearest-neighbor thermodynamic model that accurately predicts the melting thermodynamics of a short oligonucleotide duplexed either to its perfect complement or to a template containing mismatched base pairs. The model may be applied to pure-DNA duplexes or to duplexes for which one strand contains any number and pattern of LNA substitutions. Perturbations to duplex stability arising from mismatched DNA:DNA or LNA:DNA base pairs are treated at the Gibbs energy level to maintain statistical significance in the regressed model parameters. This approach, when combined with the model's accounting of the temperature dependencies of the melting enthalpy and entropy, permits accurate prediction of T(m) values for pure-DNA homoduplexes or LNA-substituted heteroduplexes containing one or two independent mismatched base pairs. Terms accounting for changes in solution conditions and terminal addition of fluorescent dyes and quenchers are then introduced so that the model may be used to accurately predict and thereby tailor the T(m) of a pure-DNA or LNA-substituted hydrolysis probe when duplexed either to its perfect-match template or to a template harboring a noncomplementary base. The model, which builds on classic nearest-neighbor thermodynamics, should therefore be of use to clinicians and biologists who require probes that distinguish and quantify two closely related alleles in either a quantitative PCR or dPCR assay. This potential is demonstrated by using the model to design allele-specific probes that completely discriminate and quantify clinically relevant mutant alleles (BRAF V600E and KIT D816V) in a dPCR assay.

The interactions between pain, pain-related fear of movement and productivity.

BACKGROUND: Employees with physically heavy work have an increased risk of musculoskeletal disorders leading to reduced work ability. AIMS: To investigate if a high level of musculoskeletal pain or pain-related fear of movement was associated with low productivity among employees with physically heavy work and differing work ability levels. METHODS: The study was conducted at a Danish production site and employees with physically heavy work in the production line were included in the study. Work ability was assessed with the Work Ability Index (WAI), pain-related fear of movement with the Tampa Scale for Kinesiophobia and productivity and musculoskeletal pain by self-reported measures. Sickness absence records for construction of WAI were obtained from the workplace. RESULTS: There was a 77% response rate with 350 employees included in the final analysis. Among employees with only moderate work ability, there was neither an association between pain and productivity nor between pain-related fear of movement and productivity. For employees with good work ability, higher levels of pain and higher levels of pain-related fear of movement both raised the odds of low productivity significantly. CONCLUSIONS: Despite the fact that musculoskeletal pain increases the risk of reduced work ability significantly, musculoskeletal pain and pain-related fear of movement were associated with low productivity only among employees with good work ability.

Impact of exercise type and dose on pain and disability in knee osteoarthritis: a systematic review and meta-regression analysis of randomized controlled trials.

OBJECTIVE: To identify the optimal exercise program, characterized by type and intensity of exercise, length of program, duration of individual supervised sessions, and number of sessions per week, for reducing pain and patient-reported disability in knee osteoarthritis (OA). METHODS: A systematic review and meta-analysis of randomized controlled trials were performed. Standardized mean differences (SMDs) were combined using a random-effects model. Study-level covariates were applied in meta-regression analyses in order to reduce between-study heterogeneity. RESULTS: Forty-eight trials were included. Similar effects in reducing pain were found for aerobic, resistance, and performance exercise (SMD 0.67, 0.62, and 0.48, respectively; P = 0.733). These single-type exercise programs were more efficacious than programs that included different exercise types (SMD 0.61 versus 0.16; P < 0.001). The effect of aerobic exercise on pain relief increased with an increased number of supervised sessions (slope 0.022 [95% confidence interval 0.002, 0.043]). More pain reduction occurred with quadriceps-specific exercise than with lower limb exercise (SMD 0.85 versus 0.39; P = 0.005) and when supervised exercise was performed at least 3 times a week (SMD 0.68 versus 0.41; P = 0.017). No impact of intensity, duration of individual sessions, or patient characteristics was found. Similar results were found for the effect on patient-reported disability. CONCLUSION: Optimal exercise programs for knee OA should have one aim and focus on improving aerobic capacity, quadriceps muscle strength, or lower extremity performance. For best results, the program should be supervised and carried out 3 times a week. Such programs have a similar effect regardless of patient characteristics, including radiographic severity and baseline pain.

Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis.

BACKGROUND: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. OBJECTIVE: To study the activation of CD4+ T cells, monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA. METHODS: Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25(high) and CD26(high) cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS patients, the latter followed prospectively for one year. Gd-enhanced magnetic resonance imaging (MRI) studies were conducted in all patients. Disease activity was assessed as relapses. RESULTS: The median percentage of DCs expressing CD40 was 10% in untreated MS patients and 5.9% in GA-treated patients (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05-1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers associated with regulatory, naïve or central memory T cell populations, but CD4+ T cell activation was not related with relapse risk. CONCLUSIONS: MS patients treated with GA show prominent changes in circulating antigen-presenting cells and CD4+ T cells. Expression of CD40 on DCs is significantly lower and associated with relapse risk in MS patients treated with GA.

Differences between questionnaire- and interview-based measures of activities of daily living (ADL) ability and their association with observed ADL ability in women with rheumatoid arthritis, knee osteoarthritis, and fibromyalgia.

OBJECTIVES: Although self-report based on questionnaire is the common method to obtain information about activities of daily living (ADL) ability in rheumatic diseases, little is known about the relationship between measures of ADL ability based on questionnaire, interview, and observation. The present study examined whether measures of self-reported ADL ability based on questionnaire and interview yielded different results, determined whether the magnitude of the difference varied among women with rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and investigated the relationships between self-reported and observed ADL ability. METHOD: The 47 ADL tasks of the ADL taxonomy were used to evaluate self-reported ADL ability based on questionnaire (ADL-Q) and interview (ADL-I), and the Assessment of Motor and Process Skills (AMPS) was used to obtain measures of observed ADL ability. RESULTS: Participants across diagnostic groups reported significantly more ADL ability based on the ADL-Q than on the ADL-I. Moderate correlations were found between the ADL-Q and ADL-I ability measures. Although low to moderate correlations were seen between measures based on the AMPS ADL motor scale and the ADL-Q and ADL-I, respectively, correlations between measures based on AMPS ADL process scale and ADL-Q and ADL-I were generally low. Overall, there was no difference in how the measures based on the two modes of self-report related to the observed ADL ability measures. CONCLUSION: Measures of self-reported ADL ability based on either questionnaire or interview have limited relationship to each other or to observed performance of ADL tasks.

Detection of drugs of abuse in simultaneously collected oral fluid, urine and blood from Norwegian drug drivers.

Blood and urine samples are collected when the Norwegian police apprehend a person suspected of driving under the influence of drugs other than alcohol. Impairment is judged from the findings in blood. In our routine samples, urine is analysed if morphine is detected in blood to differentiate between ingestion of heroin, morphine or codeine and also in cases where the amount of blood is too low to perform both screening and quantification analysis. In several cases, the collection of urine might be time consuming and challenging. The aim of this study was to investigate if drugs detected in blood were found in oral fluid and if interpretation of opiate findings in oral fluid is as conclusive as in urine. Blood, urine and oral fluid samples were collected from 100 drivers suspected of drugged driving. Oral fluid and blood were screened using LC-MS/MS methods and urine by immunological methods. Positive findings in blood and urine were confirmed with chromatographic methods. The analytical method for oral fluid included 25 of the most commonly abused drugs in Norway and some metabolites. The analysis showed a good correlation between the findings in urine and oral fluid for amphetamines, cocaine/benzoylecgonine, methadone, opiates, zopiclone and benzodiazepines including the 7-amino-benzodiazepines. Cocaine and the heroin marker 6-monoacetylmorphine (6-MAM) were more frequently detected in oral fluid than in urine. Drug concentrations above the cut-off values were found in both samples of oral fluid and urine in 15 of 22 cases positive for morphine, in 18 of 20 cases positive for codeine and in 19 of 26 cases positive for 6-MAM. The use of cannabis was confirmed by detecting THC in oral fluid and THC-COOH in urine. In 34 of 46 cases the use of cannabis was confirmed both in oral fluid and urine. The use of cannabis was confirmed by a positive finding in only urine in 11 cases and in only oral fluid in one case. All the drug groups detected in blood were also found in oral fluid. Since all relevant drugs detected in blood were possible to find in oral fluid and the interpretation of the opiate findings in oral fluid was more conclusive than in urine, oral fluid might replace urine in driving under the influence cases. The fast and easy sampling is time saving and less intrusive for the drivers.

Cognitive deficits in multiple sclerosis: correlations with T2 changes in normal appearing brain tissue.

OBJECTIVES: Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part of the cognitive impairment seen in MS and constitute a supplement to traditional measurement of T2 lesion volume. MATERIALS AND METHODS: Fifty patients with clinically definite MS were included (38 women, 12 men). Patients were MR scanned, neuropsychologically tested, and evaluated clinically with the Kurtzke Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Impairment Scale (MSIS). Voxel-wise T2 estimates and total T2 lesion volume were tested for correlations with eight cognitive domains, a general cognitive dysfunction factor (CDF), and the two clinical scales. RESULTS: We found distinct clusters of voxels with T2 estimates correlating with CDF, mental processing speed, complex motor speed, verbal fluency, and MSIS. A significant negative correlation was found between total lesion volume and CDF (r = -0.34, P = 0.02), verbal intelligence (r = -0.40, P = 0.005), mental processing speed (r = -0.34, P = 0.03), visual problem solving (r = -0.40, P = 0.01), and complex motor speed (r = -0.39, P = 0.01). No significant correlation was detected between total lesion load and the clinical measures EDSS and MSIS. CONCLUSION: Our results suggest that even in the NABT MR detects changes likely to be associated with an underlying pathology and possibly contributes to the cognitive impairment in MS.

Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis.

BACKGROUND: Glatiramer acetate (GA) treatment suppresses disease activity in multiple sclerosis (MS). The immunological response to treatment may differ in patients who are stable on GA therapy and patients with breakthrough disease activity, but the results of previous studies are inconsistent. OBJECTIVES: We studied the immunological response to GA and its relationship with disease activity. METHODS: Anti-GA antibodies in plasma and the expression of genes encoding cytokines and T-cell-polarizing transcription factors in blood cells were analysed by flow cytometric bead array and polymerase chain reaction (PCR) analysis in 39 untreated and 29 GA-treated relapsing-remitting MS patients. Definition of breakthrough disease was based on the occurrence of relapses, disability progression, or gadolinium (Gd)-enhanced MRI. RESULTS: The expression of T helper type 1 (Th1) and Th17 cytokines and transcription factors was reduced during long-term treatment, but there was no relationship between the expression of cytokines and transcription factors and anti-GA antibodies. High expression of mRNA encoding GATA3 and lymphotoxin-ß (LT-ß) was associated with low disease activity in Gd-enhanced MRI studies. None of the variables studied were associated with clinical disease activity. GA treatment resulted in the development of IgG and IgG4 anti-GA antibodies during the first months of treatment, persisting during long-term treatment. CONCLUSIONS: The observed relationship between the expression of mRNA encoding GATA3 and LT-ß expression and MRI disease activity deserves further analysis in future studies. The development of anti-GA antibodies was observed in all patients treated with GA, but this was not related with measures of cellular immunity, clinical or MRI disease activity.

Drugs of abuse in oral fluid collected by two different sample kits--stability testing and validation using ultra performance tandem mass spectrometry analysis.

Oral fluid (OF) is an alternative matrix for monitoring drugs of abuse in workplace, clinical toxicology, criminal justice, and driving under the influence of drugs (DUID). OF is suitable for detection of drugs that have been taken recently. It is unproblematic to observe the collection and hence avoid the possibility of the samples being tampered. OF often contains compounds in low concentrations, and small volumes are often collected. It is therefore necessary to have a sensitive, multi component method for drug detection. In this study an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed. The samples were prepared by liquid-liquid extraction (LLE) with ethyl acetate/heptane (4:1) and the separation was achieved by an Acquity HSS T3-column (2.1 mm × 100 mm, 1.8 µm particles). Mass detection was performed by positive ion mode electrospray MS-MS. 32 drugs of abuse were determined with a cycle time of 9 min. Stability of drugs in oral fluid before analysis is an important factor that must be evaluated for each sampling device. The collection devices Intercept(®) and StatSure Saliva Sampler™ were tested using pools of real samples containing various drugs. The testing showed that 6-MAM (6-acetylmorphine), cocaine and zopiclone were the least stable compounds. In the testing for short term stability, StatSure Saliva Sampler™ showed better results. The testing of 1 year of storage at -20°C showed that most of the compounds were stable for both sampling devices, except for 6-MAM, cocaine and zopiclone. Samples of OF should be analysed as soon as possible after collection, and they should be kept frozen if immediate analysis is not possible.

Disease protection and interleukin-10 induction by endogenous interferon-ß in multiple sclerosis?

OBJECTIVE: An immune activation response resembling virus or type I interferon responses has been observed in untreated multiple sclerosis (MS), but its pathogenic significance is uncertain. We studied the relationship between a type I interferon-like response in untreated patients with MS and disease activity. METHODS: Gene expression was analyzed by real-time reverse transcriptase polymerase chain reaction (PCR) in whole blood samples and by microarray analysis of mononuclear cells from untreated patients with MS, patients with MS treated with IFN-ß, and patients with MS with anti-IFN-ß neutralizing antibodies (NAb). Disease activity was assessed by gadolinium-enhanced magnetic resonance imaging. RESULTS: Eight of 36 untreated patients with MS had spontaneously increased expression of the type I IFN-induced gene MX1. Microarray gene expression analysis demonstrated that patients with increased spontaneous MX1 expression also had increased expression of other genes induced by regular IFN-ß treatment of MS. MX1 expression correlated with FOXP3 and IL10 expression, and IL10 expression correlated negatively with disease activity on magnetic resonance imaging. Further, in vivo IL10 expression was lower in NAb-positive patients than in untreated patients with MS and healthy controls. Finally, ex vivo treatment of mononuclear blood cells with IFN-ß induced the expression of IL10, and this was blocked by the addition of serum from NAb-positive patients with MS. CONCLUSION: Our findings suggest that endogenous IFN-ß may induce the expression of immunoregulatory IL10 in MS and that this might be associated with dampening of inflammatory disease activity.

Views on euthanasia and the rehoming of dogs in Norway and Iceland.

According to several previously published studies, large populations of dogs are sent to animal shelters in the UK and USA each year, and estimates indicate that a substantial percentage of the dogs in such shelters are euthanased annually. However, anecdotal evidence indicates a different situation in Norway and Iceland. This study explores the attitudes toward euthanasia of dogs in Norway and Iceland, and investigates the practice of rehoming of dogs in the two countries. A general reluctance toward euthanasia of dogs was expressed, and participants stressed the need to consider alternatives such as rehoming. Rehoming of dogs was found to be negligible in Norway relative to international trends, and less than 10 per cent of the dogs assigned for rehoming were euthanased. In Iceland, the rehoming of dogs is yet to reach levels that necessitate the setting up of animal shelters. There is, nevertheless, reason to continue to explore the attitudes toward euthanasia and rehoming of dogs in Norway and Iceland, because there is a lack of statistical data on the reasons behind the owners' decisions to give away or euthanase their dogs.