Clowns in Paediatric Surgery: Less Anxiety and More Oxytocin? A Pilot Study.

Background Hospital stays and medical interventions are accompanied by worries and anxiety in children and parents. Recent studies show that hospital clowns may reduce anxiety and enhance well-being. However, so far studies are based solely on subjective measures and clowns are usually not integrated in medical routine. With this pilot study, we aim to provide both psychological and physiological evidence of positive effects of clowns' interventions in hospitalized children. Patients/Method In a consecutive randomized intervention-control group design with 31 children aged 4 to 13 years, 17 patients were accompanied by a clown prior to surgery or during ward round (intervention group) and 14 were not (control group). Saliva samples for oxytocin measurement were taken from all patients before hospitalization (T1) and prior to surgery or after ward round (T2). Self- and parents-reports were obtained at T1, T2 as well as at time of discharge from hospital (T3) regarding children's anxiety (STAI), worries and well-being. Clowns evaluated their success in cheering up the child. Health professionals were asked for their acceptance of clowns in hospitals. Results Children in the intervention group had lower anxiety ratings and a higher oxytocin concentration at T2 as compared with T1; the control group showed no changes. Parents rated the well-being of their children higher if their child had clown's contact and were more willing to recommend the hospital. The staff judged the clowns as helpful for patients. Discussion Consistent psychological and physiological results suggest the positive impact of a clown's intervention in hospitalized children.

Analytical robustness of nine common assays: frequency of outliers and extreme differences identified by a large number of duplicate measurements.

INTRODUCTION: Duplicate measurements can be used to describe the performance and analytical robustness of assays and to identify outliers. We performed about 235,000 duplicate measurements of nine routinely measured quantities and evaluated the observed differences between the replicates to develop new markers for analytical performance and robustness. MATERIALS AND METHODS: Catalytic activity concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and concentrations of calcium, cholesterol, creatinine, C-reactive protein (CRP), lactate, triglycerides and thyroid-stimulating hormone (TSH) in 237,261 patient plasma samples were measured in replicates using routine methods. The performance of duplicate measurements was evaluated in scatterplots with a variable and symmetrical zone of acceptance (A-zone) around the equal line. Two quality markers were established: 1) AZ95: the width of an A-zone at which 95% of all duplicate measurements were within this zone; and 2) OPM (outliers per mille): the relative number of outliers if an A-zone width of 5% was applied. RESULTS: The AZ95 ranges from 3.2% for calcium to 11.5% for CRP and the OPM from 5 (calcium) to 250 (creatinine). Calcium, TSH and cholesterol have an AZ95 of less than 5% and an OPM of less than 50. CONCLUSIONS: Duplicate measurements of a large number of patient samples identify even low frequencies of extreme differences and thereof defined outliers. We suggest two additional quality markers, AZ95 and OPM, to complement description of assay performance and robustness. This approach can aid the selection process of measurement procedures in view of clinical needs.

Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.

Angiopoietin-2, its soluble receptor Tie-2, and metabolic syndrome components in a population-based sample.

OBJECTIVE: Since angiopoietin-2 (Ang-2) levels strongly correlate with cardiovascular mortality and subclinical cardiovascular disease, it was hypothesized that levels of Ang-2 and its soluble receptor (sTie-2) were associated with the metabolic syndrome (MetS) and individual MetS components. METHODS: Within the population-based Study of Health in Pomerania, two sets of analyses were performed. First, Ang-2 and sTie-2 were related to the prevalence of MetS and its components cross-sectionally (n = 3,205). Second, the association between baseline Ang-2 and sTie-2 and incident MetS or longitudinal changes in its components in 1,295 individuals was investigated. RESULTS: High Ang-2 levels (90th percentile), compared with low Ang-2 levels (10th percentile), were positively associated with MetS (OR: 1.78) and with the following MetS criteria: increased triglycerides, lower HDL cholesterol, and higher non-fasting glucose. Furthermore, high sTie-2 levels (90th percentile), compared with low levels (10th percentile), were positively related to MetS (OR: 1.58) and most of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or longitudinal change in components of MetS. CONCLUSIONS: Ang-2 and sTie-2 levels were cross-sectionally associated with MetS and several of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or changes in individual MetS components during follow-up.

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

Partially desulfated heparin modulates the interaction between anti-protamine/heparin antibodies and platelets.

Protamine (PRT) is the standard drug to neutralise heparin. PRT/heparin complexes induce an immune response similar to that observed in heparin-induced thrombocytopenia (HIT). Partially desulfated heparin (ODSH) was shown to interfere with anti-platelet factor 4/heparin antibodies (Abs), which are responsible for HIT. In this study, we analyse the impact of ODSH on the interaction between anti-PRT/heparin Abs and platelets. The ability of ODSH to prevent anti-PRT/heparin Ab-induced platelet destruction in vivo was investigated using the NOD/SCID mouse model. ODSH improved platelet survival in the presence of PRT, heparin and anti-PRT/heparin Abs (median platelet survival after 300 minutes (min) with 20 µg/ml ODSH: 75%, range 70-81% vs without ODSH: 49%, range 44-59%, p=0.006). Furthermore, when ODSH was applied 60 min after Ab injection platelet survival was improved (median platelet survival after 300 min with ODSH: 83%, range 77-93% vs without ODSH: 59%, range 29-61%, p=0.02). In in vitro experiments ODSH inhibited platelet activation at concentrations >16 µg/mL (p<0.001), as well as PRT/heparin complex binding to platelets (mean fluorescence intensity [MFI] without ODSH: 85 ± 14 vs with ODSH: 15 ± 0.6, p=0.013). ODSH also displaced pre-bound complexes from the platelet surface (MFI without ODSH: 324 ± 43 vs with 32 µg/ml ODSH: 53 ± 9, p<0.001). While interfering with platelet activation by anti-PRT/heparin Abs, up to a concentration of 16 µg/ml, ODSH had only minimal impact on neutralisation of heparin by PRT. In conclusion, our study shows that ODSH is able to inhibit platelet activation and destruction suggesting a potential clinical use to reduce anti-PRT/heparin Ab-mediated adverse effects.

Longitudinal effects of systemic inflammation markers on periodontitis.

AIM: Systemic low-grade inflammation represents a central hallmark of chronic diseases and has been proposed as the underlying mechanism linking factors like obesity or diabetes with periodontitis. However, the impact of inflammatory markers on periodontitis has not yet been investigated. MATERIALS AND METHODS: The study population comprised 1784 subjects from the Study of Health in Pomerania with complete 11-year follow-up. Fibrinogen and white blood cell (WBC) counts were measured as markers of inflammation. Periodontitis was assessed by probing depth (PD), clinical attachment loss (CAL) and the CDC/AAP case definition. RESULTS: Multilevel regression analyses revealed significant coefficients for the impact of both inflammation markers on the percentage of sites with PD/CAL ≥ 3 mm. Increases in fibrinogen about 1 g/l were associated with 3.0% and 2.7% more sites with PD/CAL ≥ 3 mm respectively. Consistent associations were found using mean values of PD/CAL but not using missing teeth or caries. Regarding the CDC/AAP case definition, 11-year changes in fibrinogen and WBC counts were significantly associated with ≥1 category progression (OR: 1.36 and 1.11). CONCLUSIONS: Fibrinogen levels and WBC counts showed consistent long-term associations with PD, CAL and the CDC/AAP case definition. Results indicate that systemic low-grade inflammation might indeed represent one possible pathway for effects of obesity, diabetes or other chronic inflammatory conditions on periodontitis.

Modulation of genetic associations with serum urate levels by body-mass-index in humans.

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

Angiopoietin-2, its soluble receptor Tie-2 and subclinical cardiovascular disease in a population-based sample.

OBJECTIVE: Higher circulating Angiopoietin-2 (Ang-2) levels predict cardiovascular events and mortality in clinical samples and in the general population. To better understand the underlying mechanisms, we investigated the association of circulating Ang-2 and sTie-2 (the soluble form of the Ang-2 receptor) levels with various measures of subclinical cardiovascular disease. METHODS: Cross-sectional data of 3204 participants (1654 women) aged 25-88 years from the population-based Study of Health in Pomerania were analysed. LV mass (LVM) and fractional shortening were determined echocardiographically as indices of cardiac structure and function, respectively. Intima media thickness (IMT) of the common carotid artery, the number of carotid plaques and flow-mediated dilation (FMD) were used to characterise large and medium-sized arterial structure and function. RESULTS: Multivariable-adjusted linear and negative binomial regression models revealed an inverse association of circulating Ang-2 levels (independent variable) with fractional shortening (ß=-0.51 per 1 SD increment; 95% CI -0.86 to -0.16, p=0.005) and a positive association with number of carotid plaques (rate ratio=1.04 95% CI 1.01 to 1.07, p=0.019). No associations of Ang-2 or sTie-2 with LVM, IMT and FMD were found. CONCLUSIONS: Circulating Ang-2 levels were associated with select subclinical cardiovascular disease traits, consistent with the notion that the Ang-2-pathway plays a role in mediating cardiovascular morbidity.

Association between serum vitamin D concentrations and inflammatory markers in the general adult population.

OBJECTIVE: In recent years links among vitamin D deficiency, inflammation and cardio-metabolic disease were proposed. As information regarding the associations between vitamin D and inflammatory markers in the general population is sparse, we investigated the associations of 25-hydroxy vitamin D [25(OH)D] with high-sensitivity C-reactive protein (hs-CRP), fibrinogen and white blood cell count (WBC). MATERIALS/METHODS: The study population comprised 2723 men and women aged 25-88 years from the first follow-up of the Study of Health in Pomerania. Analyses of variance, linear and logistic regressions were performed to assess the associations between 25(OH)D and the three inflammatory markers. The models were adjusted for age, sex, waist circumference, diabetes mellitus, dyslipidemia, anti-inflammatory medication and month of blood sampling. The association between 25(OH)D and WBC was assessed separately in smokers (n = 718) and non-smokers (n = 2005) as effect modification was observed. RESULTS: We detected a U-shaped association between 25(OH)D and hs-CRP with a nadir of 21-25 ng/ml in fully-adjusted linear regression models with restricted cubic splines (p < 0.01; p' < 0.01). We further detected an inverse association between 25(OH)D and fibrinogen (p < 0.01). In addition, there was an inverse association between 25(OH)D and WBC in smokers (p = 0.02) but no association in non-smokers (p = 0.73). CONCLUSION: Our study confirms a potential role of 25(OH)D in chronic inflammation. Yet, different inflammatory biomarkers are differently associated with 25(OH)D. Beneficial effects of increasing 25(OH)D were observed for fibrinogen and WBC (in smokers only). In contrast, the U-shaped association between 25(OH)D and hs-CRP indicates that ever-increasing 25(OH)D concentrations may also be related to proinflammatory states.

Abdominal obesity modifies long-term associations between periodontitis and markers of systemic inflammation.

OBJECTIVE: Periodontitis is considered to promote atherosclerosis and cardiovascular diseases through increased low-grade systemic inflammation. However, there is no information on the long-term impact of periodontitis on systemic inflammation from cohort studies. Thus, this study aims to assess the impact of periodontitis on systemic inflammation (fibrinogen and white blood cells (WBC)) in a population-based longitudinal survey in north-eastern Germany. METHODS: The study sample comprised 2622 subjects from the Study of Health in Pomerania with complete 5- and 11-year follow-ups. Periodontitis was assessed by probing depth and clinical attachment level. Multilevel regression analyses were applied to evaluate associations between periodontitis measures and i) fibrinogen/WBC count using 11-year follow-up data and ii) respective z-scores of fibrinogen/WBC count using 5- and 11-year follow-up data. We adjusted for common cardiovascular risk factors and stratified analyses by abdominal obesity (P for interaction <0.10). RESULTS: In lean subjects, beta-coefficients of mean probing depth were B = 0.13 (0.08-0.019; P < 0.001) for fibrinogen and B = 0.50 (0.37-0.64; P < 0.001) for WBC count using 11-year follow-up data only. For lean subjects, models using z-scores confirmed that increased mean probing depths were associated with increased fibrinogen z-scores (B = 0.14 (0.09-0.18; P < 0.001)) and increased WBC z-scores (B = 0.16 (0.11-0.20; P < 0.001)). Consistent results were found for mean clinical attachment levels. For abdominally obese subjects, relations between periodontitis measures and levels of inflammation markers were less pronounced or non-significant. CONCLUSION: Modified by abdominal obesity, periodontitis affected systemic inflammation in a significant dose-dependent manner. Results contribute to the discussion on how periodontitis is linked to atherosclerosis and cardiovascular diseases.

Acquired hemophilia with inhibitors presenting as an emergency: misinterpretation of clotting results during direct oral anticoagulation.

BACKGROUND: Direct oral anticoagulants (DOACs) were recently introduced and are being increasingly prescribed. Most DOACs alter the values of traditional coagulation tests, such as the international normalized ratio (INR) or the activated partial thromboplastin time (aPTT). Although vitamin K antagonists raise the INR value to an extent that mirrors their anticoagulant effect, DOACs do not, in general, alter standard clotting values in any consistent way. Thus, there is a risk that abnormal INR and aPTT values can be misinterpreted. CASE ILLUSTRATION: A woman taking rivaroxaban, a DOAC, presented with ileus and was scheduled for urgent surgery. A prolonged aPTT was, at first, wrongly attributed to rivaroxaban, delaying the correct diagnosis of autoantibody-associated acquired hemophilia (a rare condition with incidence, 1.34-1.48 cases per million people per year). The patient had a history of unusually intense bleeding in the skin and mucous membranes during anticoagulant treatment. Her aPTT had been prolonged even before any anticoagulants were taken. COURSE: The operation was delayed to await the elimination of rivaroxaban. The aPTT was still prolonged 24 hours later. The diagnosis of autoantibody-associated acquired hemophilia was suspected and then confirmed by the measurement of a factor VIII residual activity of 1% and the demonstration of factor VIII inhibition at an intensity of 9.2 Bethesda units per mL. CONCLUSION: The causes of abnormal clotting test results must be clarified before beginning anticoagulant therapy. Unusually intense bleeding during oral anticoagulation should arouse suspicion of a previously undiagnosed acquired coagulopathy, e.g., antibody-associated acquired hemophilia.

Cross-sectional and longitudinal relation of IGF1 and IGF-binding protein 3 with lipid metabolism.

BACKGROUND: Previous intervention studies in patients with GH disorders suggested an impact of IGF1 and IGF-binding protein 3 (IGFBP3) on lipid metabolism, whereas population-based studies revealed conflicting results. Therefore, we aimed to assess the cross-sectional and longitudinal associations between IGF1 or IGFBP3 serum levels and lipids (total, LDL, or HDL cholesterol and triglycerides) in a large-scale study. METHODS: Data of 2935 subjects (1356 women) from the population-based Study of Health in Pomerania (SHIP) were used. ANOVA, quantile regression, and logistic regression models adjusted for age, waist circumference, physical activity, and alcohol consumption were performed. RESULTS: In cross-sectional analyses, we detected that IGF1 and IGFBP3 levels were positively related to total and LDL cholesterol and inversely related to HDL cholesterol in both sexes. Furthermore, IGFBP3 levels showed a positive relationship to triglycerides. In total, IGFBP3 levels were more strongly associated to lipids than IGF1. In longitudinal analysis, we found no influence of baseline IGF1 or IGFBP3 serum concentration on incidentally elevated or reduced lipid levels. However, the positive relationship between IGFBP3 and incidentally elevated triglycerides barely missed statistical significance in women. CONCLUSION: The present study showed strong cross-sectional associations between IGF1 or IGFBP3 and lipids, whereas no longitudinal relationships were revealed. Therefore, our findings suggest IGF1 and IGFBP3 as a risk marker rather than a risk factor for alterations in lipid metabolism. Further studies are needed to elucidate the mechanisms underlying the association between the GH/IGF axis and lipid metabolism.

Optimizing centrifugation of coagulation samples in laboratory automation.

BACKGROUND: High acceleration centrifugation conditions are used in laboratory automation systems to reduce the turnaround time (TAT) of clinical chemistry samples, but not of coagulation samples. This often requires separate sample flows. The CLSI guideline and manufacturers recommendations for coagulation assays aim at reducing platelet counts. For measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT) platelet counts (Plt) below 200×10(9)/L are recommended. Other coagulation assays may require even lower platelet counts, e.g., less than 10 × 10(9)/L. Unifying centrifugation conditions can facilitate the integration of coagulation samples in the overall workflow of a laboratory automation system. METHODS: We evaluated centrifugation conditions of coagulation samples by using high acceleration centrifugation conditions (5 min; 3280×g) in a single and two consecutive runs. RESULTS of coagulation assays [PT, APTT, coagulation factor VIII (F. VIII) and protein S] and platelet counts were compared after the first and second centrifugation. RESULTS: Platelet counts below 200×10(9)/L were obtained in all samples after the first centrifugation and less than 10 × 10(9)/L was obtained in 73% of the samples after a second centrifugation. Passing-Bablok regression analyses showed an equal performance of PT, APTT and F. VIII after first and second centrifugation whereas protein S measurements require a second centrifugation. CONCLUSIONS: Coagulation samples can be integrated into the workflow of a laboratory automation system using high acceleration centrifugation. A single centrifugation was sufficient for PT, APTT and F. VIII whereas two successive centrifugations appear to be sufficient for protein S activity.

Relation of insulin-like growth factor-I and IGF binding protein 3 with markers of inflammation: results of a population-based study.

OBJECTIVE: Previous studies in acromegaly and growth hormone deficiency observed inverse associations between insulin-like growth factor-I (IGF-I) levels and inflammatory biomarkers including high-sensitive C-reactive protein (hsCRP), interleukin-6 or fibrinogen. We aimed to assess the relations between IGF-I or IGF binding protein 3 (IGFBP-3) levels and hsCRP, interleukin-6, fibrinogen and white blood cell count (WBC) in a population-based sample. DESIGN AND PATIENTS: Data from 3480 subjects from the population-based Study of Health in Pomerania (SHIP) were used. IGF-I, IGFBP-3 and inflammatory biomarkers were measured. Analysis of variance (anova), quantile regression models and logistic regression models, adjusted for age, smoking, diabetes mellitus and waist circumference, were performed. MEASUREMENTS AND RESULTS: anova and/or quantile regression showed inverse associations between IGF-I and hsCRP as well as positive associations between IGF-I and fibrinogen among both sexes. Furthermore, the odds of elevated fibrinogen levels increased with increasing IGF-I levels (per SD IGF-I increase: men: odds ratio (OR) 1·35 [95% confidence interval (CI) 1·04, 1·55]; women: OR 1·44 [95% CI 1·21, 1·71]) in both sexes, whereas the odds of increased hsCRP (women: OR 0·46 [95% CI 0·36, 0·58]) and interleukin-6 (men: odds ratio (OR) 0·77 [95% CI 0·61, 0·96]; women: OR 0·69 [95% CI 0·55, 0·86]) decreased. CONCLUSION: Serum IGF-I levels are associated with inflammatory biomarkers including hsCRP, interleukin-6 and fibrinogen. Further experimental studies are needed to elucidate the mechanisms underlying the relation between the GH/IGF axis and the inflammatory system.

Circulating angiopoietin-2, its soluble receptor Tie-2, and mortality in the general population.

AIMS: To assess the association of circulating concentrations of angiopoietin-2 (Ang-2) and its soluble receptor Tie-2 (sTie-2) with all-cause, cardiovascular, and cancer mortality in a population-based sample. METHODS AND RESULTS: Angiopoietin-2 and sTie-2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were estimated using Cox proportional hazard models. During a median follow-up of 6.2 years, 217 participants died. Ang-2 levels were positively associated with all-cause mortality [HR 1.29; 95% confidence interval (CI) 1.19-1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18-1.49; P < 0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89-1.32; P = 0.416). Levels of sTie-2 were not significantly related to all-cause mortality (HR 1.12; 95% CI 0.98-1.27; P = 0.102). Adding Ang-2 to a prediction model for all-cause mortality with standard risk factors slightly improved discrimination (Δ Harrell's C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, -0.015; P = 0.571). CONCLUSION: In our community-based sample, higher serum Ang-2 concentrations were associated with greater risk for all-cause and cardiovascular mortality, suggesting that subtle increases in Ang-2 levels might reflect processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang-2 to a mortality prediction model only modestly improved discrimination.

Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.

Short-term changes of the urine metabolome after bariatric surgery.

Bariatric surgery leads to a loss of excess weight and to a remission of diabetes in a majority of patients. In an attempt to explain these underlying mechanisms, a broad range of metabolic alterations have been suggested. We aimed to investigate short-term changes in the urinary metabolome after bariatric surgery. Data for 50 patients who underwent bariatric surgery at the Municipal Hospital of Dresden-Neustadt, Germany, were used. Healthy controls were selected from the Study of Health in Pomerania. Non-fasting, spontaneous urine samples were collected, (1)H NMR spectroscopic analysis was performed, and metabolites were quantified (Chenomx NMR suite). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) models were carried out (pre-operative versus controls, and post-operative versus controls). On the basis of the urine metabolome separations between pre-operative (predictive ability Q2Y=85.6%; total explained variance R2X=58.3%), or post-operative (Q2Y=82.1%; R2X=44.4%) and controls were possible. Metabolites including hippuric acid, 3-hydroxybutyrate, 2-hydroxyisobutyrate, and trigonelline, were altered among patients. In obese patients, 2-hydroxyisobutyrate levels were higher, whereas trigonelline and hippuric acid levels were lower than in controls. The highest levels of 3-hydroxybutyrate were found in post-operative samples, whereas the metabolite was not present in controls, and only at low levels in pre-operative samples. In conclusion, we demonstrated that the urinary metabotype differs between obese patients and healthy controls. The metabolic alterations identified after bariatric procedures increase our knowledge about the metabolic traits associated with weight reduction. Whether urinary metabotypes might be used for early prediction of a successful bariatric procedure should be evaluated in long-term observations.

Ethylene-promoted versus ethylene-free enyne metathesis.

The role of ethylene in promoting metathesis of acetylenic enynes is probed within the context of ring-closing enyne metathesis, using first- and second-generation Grubbs catalysts. Under inert atmosphere, rapid catalyst deactivation is observed by calibrated GC-FID analysis for substrates with minimal propargylic bulk. MALDI-TOF mass spectra reveal a Ru(enyne)(2) derivative that exhibits very low reactivity toward both enyne and ethylene. Under ethylene, formation of this species is suppressed. Enynes with bulky propargylic groups are not susceptible to this catalyst deactivation pathway, even under N(2) atmosphere.

Efficient and selective telomerization of 1,3-butadiene with diols catalyzed by palladium-carbene complexes.

The selective telomerization of 1,3-butadiene with seven different linear and cyclic diols proceeds in the presence of in situ generated palladium carbene catalysts. By applying optimized reaction conditions, including very low metal loadings (2-10 ppm), excellent catalyst turnover numbers (>250,000) and good chemoselectivities are observed with respect to the mono-octadienyl ether derivatives. This protocol allows the efficient preparation of unsaturated alcohols, which are useful for various applications.