Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis.

Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)-κB signalling pathways have been reported associated with responsiveness to tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis (RA). The present study was undertaken to replicate these findings. In a retrospective case-case study including 1007 Danish anti-TNF-treated RA patients, we genotyped 7 previously reported associated single-nucleotide polymorphisms (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60-0.94, P=0.014) with a negative treatment response. Meta-analyses combining data from previous studies suggested smaller effect sizes of associations between variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative treatment response. In conclusion, this study validates rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response, and suggests true positive associations of previously reported SNPs within genes encoding activators/inhibitors of NF-κB (CHUK, MYD88, NFKBIB, and NLRP3).

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1ß levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.

Validation of the register-based lifetime antimicrobial usage measurement for finisher batches based on comparison with recorded antimicrobial usage at farm level.

Assessing the relationship between antimicrobial usage (AMU) and antimicrobial resistance (AMR) requires the accurate and precise utilisation of register data. Therefore, validation of register-based data is essential for evaluating the quality and, subsequently, the internal validity of studies based on the data. In this study, different smoothing methods for Veterinary Medicine Statistic Program database (VetStat)-records were validated by comparing these with farm-records. Comparison between measurements included accuracy as; completeness and correctness, and precision as; a relative difference of the error, correlation with Fisher's z transformation and reliability coefficient. The most valid methods of those examined were then used in re-analyses of the abundance of AMR genes in 10 finisher batches from a previous study. Improved accuracy was found when detailed smoothing methods were applied. Although the precision also increased, the effect was not as pronounced, as the usage estimate of all smoothing methods deviated moderately compared with the farm-registrations. Applying the most valid methods to the 10 finisher batches increased estimates of statistical model fit for aminoglycosides, lincosamides, tetracyclines and decreased estimates of statistical model fit for macrolides. The estimates of statistical model fit for sulfonamides and broad-spectrum penicillins remained the same. Through refined data transformation, VetStat-records can be used to calculate a daily amount of AMU per pig reflecting the true usage accurately and moderately precisely, which is the foundation for calculating lifetime AMU.

Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFκB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.

The association between measurements of antimicrobial use and resistance in the faeces microbiota of finisher batches.

The objectives were to present three approaches for calculating antimicrobial (AM) use in pigs that take into account the rearing period and rearing site, and to study the association between these measurements and phenotypical resistance and abundance of resistance genes in faeces samples from 10 finisher batches. The AM use was calculated relative to the rearing period of the batches as (i) 'Finisher Unit Exposure' at unit level, (ii) 'Lifetime Exposure' at batch level and (iii) 'Herd Exposure' at herd level. A significant effect on the occurrence of tetracycline resistance measured by cultivation was identified for Lifetime Exposure for the AM class: tetracycline. Furthermore, for Lifetime Exposure for the AM classes: macrolide, broad-spectrum penicillin, sulfonamide and tetracycline use as well as Herd Unit Exposure for the AM classes: aminoglycoside, lincosamide and tetracycline use, a significant effect was observed on the occurrence of genes coding for the AM resistance classes: aminoglycoside, lincosamide, macrolide, ß-lactam, sulfonamide and tetracycline. No effect was observed for Finisher Unit Exposure. Overall, the study shows that Lifetime Exposure is an efficient measurement of AM use in finisher batches, and has a significant effect on the occurrence of resistance, measured either by cultivation or metagenomics.

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.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease.

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1ß, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.

Muscle activation and strength in squat and Bulgarian squat on stable and unstable surface.

The aim of the study was to compare muscle activity using the same relative resistance in squats and Bulgarian squats on stable and unstable surface. Muscle strength and activity were assessed by 6-repetition maximum and concomitant surface electromyography. A cohort of 15 resistance-trained males performed the exercises on the floor or a foam cushion in randomized order. The muscle activity was greater in biceps femoris (63-77%, p<0.01) and core muscle external obliques (58-62%, p<0.05) for the Bulgarian squat compared to regular squats, but lower for rectus femoris (16-21%, p<0.05). Only Bulgarian squat showed differences concerning the surface, e. g. the unstable surface reduced the activation of erector spinae (10%, p<0.05) and biceps femoris (10%, p<0.05) compared to a stable surface. There were similar activations in the vasti muscles and rectus abdominis between the different exercises (p=0.313-0.995). Unstable surfaces resulted in a load decrement of 7% and 10% compared to stable surfaces (p<0.001). In conclusion, the squat was somewhat favorable for the activation of agonists, whereas Bulgarian squat was advantageous for the antagonist and somewhat for core muscles. Bulgarian- and regular squats complement each other, and it may be useful to include both in a periodized resistance training program.

The experience of laser light feedback in back-squat resistance training.

Introduction: The purpose of this paper is to contribute to the existing literature on performance in resistance training (RT) by addressing how a phenomenological perspective on experiences with inter kinaesthetic affectivity can illuminate experience of practicing RT with non-verbal, visual feedback provided through laser lights attached to the barbell. Method: The material is created from qualitative interviews and using inter-kinaesthetic affectivity as analytical lenses. Results: The findings show how participants interpret the feedback in the moment and explain how they adjust their movement in dialogue with the feedback and enable the "uptake" of feedback in their embodied experience. The findings show how the participants developed an awareness of how they can equalize the balance on their feet. Discussion: We discuss what this means for the understanding of the training process in terms of how practitioners can use the uptake of non-verbal, visual feedback to immediately adjust the quality of their performance by responding kinaesthetically and bodily. The discussion contributes to the question of what kind of role a practitioner's own kinaesthetic and bodily experiences have in the development and organization of RT. Perspectives that include the lived and intersubjective body as a knowledge position are promising for illuminating the whole bodied engagement that is necessary to understand how to perform RT.

The quantitative effect of antimicrobial usage in Danish pig farms on the abundance of antimicrobial resistance genes in slaughter pigs.

Research has long established the connection between antimicrobial use (AMU) and antimicrobial resistance (AMR) in production animals, and shown that the ceasing of AMU reduces AMR. Our previous study of Danish slaughter-pig production found a quantitative relationship between lifetime AMU and abundance of antimicrobial resistance genes (ARGs). This study aimed to generate further quantitative knowledge on how changes in AMU in farms influence the abundance of ARGs both with immediate effect and over time. The study included 83 farms that were visited from 1 to 5 times. From each visit, a pooled faecal sample was produced. The abundance of ARGs was obtained by metagenomics. We used two-level linear mixed models for estimating the effect of AMU on the abundance of ARGs against six antimicrobial classes. The lifetime AMU of each batch was calculated from usage during their three rearing periods; as piglets, weaners and slaughter pigs (rearing pathway). AMU at farm level was estimated as the mean lifetime AMU of the sampled batches from each farm. At batch level, AMU was measured as the deviation between the batch-specific lifetime AMU and the general mean lifetime AMU at the farm. For peroral tetracycline and macrolide use there was a significant quantitative linear effect on the abundance of ARGs in batches within individual farms, indicating an immediate effect of changed AMU from batch to batch within farms. These estimated effects between batches within farms were approximately 1/2-1/3 of the effect estimated between farms. For all antimicrobial classes, the effect of the mean farm-level AMU and the abundance of ARGs present in the faeces of slaughter pigs was significant. This effect was identified only for peroral use, except for lincosamides, where the effect was for parenteral use. The results also indicated that the abundance of ARGs against a specific antimicrobial class also increased by the peroral usage of one or several other antimicrobial classes, except for ARGs against beta-lactams. These effects were generally lower than the AMU effect of the specific antimicrobial class. Overall, the farm peroral mean lifetime AMU affected the abundance of ARGs at antimicrobial class level and abundance of ARGs of other classes. However, the difference of AMU of the slaughter-pig batches affected only the abundance of ARGs at the same antimicrobial class level in the same antimicrobial class. The results do not exclude that parenteral usage of antimicrobials may have an effect on the abundance of ARGs.

The effects of technological and traditional feedback on back squat performance in untrained women.

BACKGROUND: Recently, a novel method for improving movement quality called open-ended augmented feedback has been introduced. However, the effects of using such feedback in a training intervention have not yet been examined. The aim of this study was to assess the changes in performance and movement quality following a five-week resistance-training program with either (1) technological feedback or (2) traditional, verbal feedback from an experienced trainer. METHODS: Nineteen untrained females (age: 21.84 ± 2.24 years, height: 169.95 ± 5.92 cm, body mass: 65.05 ± 7.93 kg) randomly allocated to one of the two conditions completed five weeks of training with two weekly sessions. Pre- and post-intervention, participants were tested for physical performance (i.e., back squat and isometric mid-thigh pull strength) and movement quality parameters (weight distribution, center of gravity variation, and subjective rating of the back squat technique). RESULTS: Both groups similarly increased the training resistance throughout the intervention (p < 0.01), as well as strength in the back squat (technological feedback group: effect size (ES) = 1.31, p = 0.002; traditional feedback group: ES = 1.48, p = 0.002). Only the traditional feedback group increased isometric mid-thigh pull strength (ES = 1.11, p = 0.008) and subjectively rated lifting technique at the same load (p = 0.046). No changes in force distribution (p = 0.062-0.993) or center of gravity variation (p = 0.160-0.969) occurred in either group when lifting the same absolute loads at post-test. However, both groups displayed a greater variation in center of gravity when lifting the same relative load at post-test (technological feedback group: p < 0.001; traditional feedback group: p = 0.006). No differences were found between the groups for any of the observed changes (p = 0.205-0.401). CONCLUSIONS: Five weeks of back-squat training with verbal feedback increased isometric mid-thigh pull strength and subjectively rated lifting technique from pre- to post-test, whereas technological feedback did not. Both methods improved back squat strength and training resistance. For resistance-training beginners, the choice between feedback methods should be based on the desired outcomes and the availability of expertise and equipment.

Atmospheric chemistry of C2F5CH2OCH3 (HFE-365mcf).

FTIR smog chamber techniques were used to measure k(Cl + C(2)F(5)CH(2)OCH(3)) = (2.52 ± 0.37) × 10(-11) and k(OH + C(2)F(5)CH(2)OCH(3)) = (5.78 ± 1.02) × 10(-13) cm(3) molecule(-1) s(-1) in 700 Torr of air diluent at 296 ± 1 K. The atmospheric lifetime of C(2)F(5)CH(2)OCH(3) is estimated to be 20 days. Reaction of chlorine atoms with C(2)F(5)CH(2)OCH(3) proceeds 18 ± 2% at the -CH(2)- group and 82 ± 2% at the -CH(3) group. Reaction of OH radicals with C(2)F(5)CH(2)OCH(3) proceeds 44 ± 5% at the -CH(2)- group and 56 ± 5% at the -CH(3) group. The atmospheric fate of C(2)F(5)CH(2)OCH(2)O radicals is reaction with O(2) to give C(2)F(5)CH(2)OCHO. The atmospheric fate of C(2)F(5)CH(O)OCH(3) radicals is C-C bond-cleavage to give C(2)F(5) radicals and CH(3)OCHO (methyl formate). The infrared spectrum was recorded and used to estimate a global warming potential of 6 (100 year time horizon) for C(2)F(5)CH(2)OCH(3).

Biocompatibility and pathways of initial complement pathway activation with Phisio- and PMEA-coated cardiopulmonary bypass circuits during open-heart surgery.

A randomized open-heart surgery study comprising 30 patients was undertaken to compare the biocompatibility of Phisio-(phosphorylcholine) and PMEA-(poly-2-methoxyethyl acrylate) coated cardiopulmonary bypass (CPB) circuits and to assess the initial complement pathway activation during open-heart surgery. Blood samples were obtained at five time points, from the start of surgery to 24 hours postoperatively. The following analyses were performed: haemoglobin, lactate dehydrogenase, leukocyte and platelet counts, myeloperoxidase and neutrophil-activating peptide-2, thrombin-anti-thrombin complexes, syndecan-1 and the complement activation products C1rs-C1-inhibitor complexes, C4bc, C3bc, C3bBbP and the terminal complement complex (TCC). No significant inter-group difference was found in any parameters, except for the concentration of TCC which was moderately lower in the PMEA group at termination of CPB. Complement activation during open-heart surgery was mainly mediated through the alternative pathway. In conclusion, PMEA- and Phisio-coated circuits displayed similar biocompatibility with respect to inflammatory and haemostatic responses during and after open-heart surgery.

The effect of N-3 fatty acids on plasma myeloperoxidase levels in healthy adults.

OBJECTIVE: To examine the effect of marine n-3 polyunsaturated fatty acids (PUFA) supplementation in a low to moderate and a high dose on plasma levels of myeloperoxidase (MPO) in healthy individuals. BACKGROUND: Atherosclerosis is a chronic inflammatory disease and MPO, which is secreted primarily from activated neutrophils and monocytes, has pro-inflammatory properties and has been linked with both initiation and propagation of atherosclerosis. Marine n-3 PUFA have anti-inflammatory properties, but whether n-3 PUFA affect plasma levels of MPO is largely unknown. METHODS: Sixty healthy adults were randomized to three groups receiving either 6.6 g PUFA/day, 2.0 g PUFA/day or a control oil (olive oil) for 12 weeks. Blood samples were drawn at baseline and after exposure. Plasma levels of MPO were measured using a MPO ELISA-kit (from Mercodia, Uppsala, Sweden) with specific mouse monoclonal antibodies. RESULTS: Plasma MPO concentrations (microg/L) at baseline were 36.9 +/- 9.4; 36.2 +/- 7.1 and 35.4 +/- 11.3 (for high dose-, low dose- and control-group, respectively). After 12 weeks of supplementation we found no significant changes in plasma MPO in any of the groups nor between groups, with values after intervention of 36.1 +/- 8.6; 37.0 +/- 8.2 and 34.4 +/- 11.1, respectively. CONCLUSION: Supplementation with n-3 PUFA has no effect on plasma levels of MPO in healthy adults with low baseline levels of MPO.

Serum concentrations of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 and alpha2-macroglobulin in healthy subjects after supplementation with different doses of marine n-3 fatty acids.

OBJECTIVE: Extracellular matrix modification by matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and alpha2-macroglobulin may affect the stability of atherosclerotic plaques. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against plaque rupture. The aim was to investigate the effect of marine n-3 PUFA supplementation on serum levels of MMP-9, TIMP-1, and alpha2-macroglobulin. METHODS: Healthy volunteers were randomized to receive capsules contributing either 6.6 g marine n-3 PUFA/day, 2.0 g marine n-3 PUFA/day or 6.6 g of olive oil (control). Serum MMP-9, TIMP-1 and alpha2-macroglobulin was measured at baseline and after 12 weeks of supplementation. One way ANOVA or Kruskal-Wallis test was used to compare groups. RESULTS: 60 healthy volunteers were enrolled and no subjects dropped out of the 12 week study. There were no statistically significant changes in serum levels of MMP-9, TIMP-1, and alpha2-macroglobulin in any of the three treatment groups (P=0.85, P=0.23 and P=0.87, respectively). CONCLUSION: Supplementation with marine n-3 PUFA had no effect on serum levels of MMP-9, TIMP-1 and alpha2-macroglobulin in healthy subjects. The possible protection offered by marine n-3 PUFA against plaque rupture is therefore unlikely to be mediated through a change in serum levels of MMP-9, TIMP-1 and alpha2-macroglobulin.

Atmospheric chemistry of i-butanol.

Smog chamber/FTIR techniques were used to determine rate constants of k(Cl + i-butanol) = (2.06 ± 0.40) × 10(-10), k(Cl + i-butyraldehyde) = (1.37 ± 0.08) × 10(-10), and k(OH + i-butanol) = (1.14 ± 0.17) × 10(-11) cm(3) molecule(-1) s(-1) in 700 Torr of N(2)/O(2) diluent at 296 ± 2K. The UV irradiation of i-butanol/Cl(2)/N(2) mixtures gave i-butyraldehyde in a molar yield of 53 ± 3%. The chlorine atom initiated oxidation of i-butanol in the absence of NO gave i-butyraldehyde in a molar yield of 48 ± 3%. The chlorine atom initiated oxidation of i-butanol in the presence of NO gave (molar yields): i-butyraldehyde (46 ± 3%), acetone (35 ± 3%), and formaldehyde (49 ± 3%). The OH radical initiated oxidation of i-butanol in the presence of NO gave acetone in a yield of 61 ± 4%. The reaction of chlorine atoms with i-butanol proceeds 51 ± 5% via attack on the α-position to give an α-hydroxy alkyl radical that reacts with O(2) to give i-butyraldehyde. The atmospheric fate of (CH(3))(2)C(O)CH(2)OH alkoxy radicals is decomposition to acetone and CH(2)OH radicals. The atmospheric fate of OCH(2)(CH(3))CHCH(2)OH alkoxy radicals is decomposition to formaldehyde and CH(3)CHCH(2)OH radicals. The results are consistent with, and serve to validate, the mechanism that has been assumed in the estimation of the photochemical ozone creation potential of i-butanol.

Comparable biocompatibility of Phisio- and Bioline-coated cardiopulmonary bypass circuits indicated by the inflammatory response.

BACKGROUND: The biocompatibility of cardiopulmonary bypass surfaces has been improved by heparin and polymer surface modifications. The present study compared the effect of two such coatings on the inflammatory reactions after open heart surgery. METHODS: Thirty patients undergoing elective heart surgery were randomly assigned to receive one of two types of coated circuits: Bioline (n=15) or phosphorylcholine (Phisio, n=15). The platelet and leukocyte counts, neutrophil activation (myeloperoxidase), complement activation (C3a and TCC), concentrations of lactate dehydrogenase, 27 cytokines (including interleukins, chemokines and growth factors), thrombin-antithrombin complexes, and the endothelial cell marker syndecan-1 were analyzed at five predetermined time points until 24 hrs post operatively. RESULTS: Most measurements were comparable in both groups. However, myeloperoxidase was significantly higher in the Bioline group (p < 0.001). Postoperative lactate dehydrogenase concentrations were significantly higher in the Phisio group (p<0.01) and the maximal concentration of thrombin-antithrombin complexes 2 hours postoperatively tended to be higher in the Phisio group (p=0.08), consistent with a longer aortic cross-clamp and cardiopulmonary bypass time. CONCLUSIONS: The two circuits exhibited a comparable degree of in vivo biocompatibility.

Predicting effects of changed antimicrobial usage on the abundance of antimicrobial resistance genes in finisher' gut microbiomes.

It is accepted that usage of antimicrobials (AMs) in food animals causes the emergence and spread of antimicrobial resistance (AMR) in this sector, while also contributing to the burden of AMR in humans. Curbing the increasing occurrence of AMR in food animals requires in-depth knowledge of the quantitative relationship between antimicrobial usage (AMU) and AMR to achieve desired resistance reductions from interventions targeting AMU. In the observational study, the relationships between lifetime AMU in 83 finisher batches from Danish farms and the AMR gene abundances of seven antimicrobial classes in their gut microbiomes were quantified using multi-variable linear regression models. These relationships and the national lifetime AMU in pigs were included in the predictive modelling that allowed for testing of scenarios with changed lifetime AMU for finishers produced in Denmark in 2014. A total of 50 farms from the observational study were included in validating the observational study and the predictive modelling. The results from the observational study showed that the relationship was linear, and that the parenteral usage of AMs had a high effect on specific AM-classes of resistance, whereas the peroral usage had a lower but broader effect on several classes. Three different scenarios of changed lifetime AMU were simulated in the predictive modelling. When all tetracycline usage ceased, the predicted interval reductions of aminoglycoside, lincosamide and tetracycline resistance were 4-42 %, 0-8 % and 9-18 %, respectively. When the peroral tetracycline usage of the 10 % highest users was replaced with peroral macrolide usage, the tetracycline resistance fell by 1-2 % and the macrolide and MLSb resistance increased by 5-8 %. When all extended-spectrum penicillin usage was replaced with parenteral lincosamide usage, the beta-lactam resistance fell by 2-7 %, but the lincosamide usage and resistance increased by 194 % and 10-45 %, respectively. The external validation provided results within the 95 % CI of the predictive modelling outcome at national level, while the external validation at farm level was less accurate. In conclusion, interventions targeting AMU will reduce AMR abundance, though differently depending on the targeted AM-class and provided the reduction of one AM-class usage is not replaced with usage of another AM-class. Predicting several classes of AMR gene abundance simultaneously will support stakeholders when deciding on interventions targeting AMU in the finisher production to avoid adverse and unforeseen effects on the AMR abundance. This study provides a sound predictive modelling framework for further development, including the dynamics of AMU on AMR in finishers at national level.