The role of APRIL and BAFF in lymphocyte activation.

The TNF family ligands BAFF (also called BLyS) and APRIL regulate lymphocyte survival and activation. BAFF binds to three receptors, BAFF-R, TACI and BCMA, whereas APRIL interacts with TACI, BCMA and proteoglycans. The contribution of BAFF and APRIL to B-cell and plasma-cell survival, CD154 (CD40L)-independent antibody isotype switching, germinal center maintenance, T-dependent and T-independent antibody responses, and T cell co-stimulation are relatively well understood. Constitutive BAFF produced by stromal cells determines the size of the peripheral B cell pool, whereas inducible BAFF produced by myeloid and other cells supports local survival of B lymphocytes and can be associated with development of autoimmunity when deregulated.

Could moderate alcohol consumption help prevent the metabolic syndrome and diabetes mellitus ?

Aim and purpose: Moderate alcohol consumption has been associated with lower risk of diabetes mellitus, but few data exist on the metabolic syndrome and on the metabolic impact of heavy drinking. The aim of our study was to investigate the complex relationship between alcohol and the metabolic syndrome and diabetes mellitus in a population-based study in Switzerland with high mean alcohol consumption. Design and methods: In 6188 adults aged 35 to 75, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and >= 35 drinks/week or as nondrinkers, moderate (1-13 drinks), high (14-34 drinks) and very high (>= 35 drinks) alcohol consumption. The metabolic syndrome was defined according to the ATP-III criteria and diabetes mellitus as fasting glycemia >= 7 mmol/l or self-reported medication.We used multivariate analysis adjusted for age, gender, smoking status, physical activity and education level to determine the prevalence of the conditions according to drinking categories. Results: 73% (n = 4502) of the participants consumed alcohol, 16% (n = 993) were high drinkers and 2% (n = 126) very high drinkers. In multivariate analysis, alcohol consumption had a U-shaped relationship with the metabolic syndrome and diabetes mellitus. The prevalence of the metabolic syndrome significantly differed between nondrinkers (24%), moderate (19%), high (20%) and very high drinkers (29%) (P<= 0.005). The prevalence of diabetes mellitus also significantly differed between nondrinkers (6.0%), moderate (3.6%), high (3.8%) and very high drinkers (6.7%) (P<= 0.05). These relationships did not differ according to beverage types. Conclusions: The prevalence of the metabolic syndrome and diabetes mellitus decrease with moderate alcohol consumption and increase with heavy drinking, without differences according to beverage types. Recommending to limit alcohol consumption to 1-2 drinks/day might help prevent these conditions in primary care Metabolic Syndrome and Diabetes Mellitus.

Rare earth elements and stable isotope geochemistry (δ13C and δ18O) of phosphorite deposits in the Gafsa Basin, Tunisia

Rare earth elements (REE) and stable isotope compositions (delta C-13 and delta O-18) of shark teeth and phosphatic coprolites were analyzed from the Lower Maastrichtian layers of the El Haria Formation and two sequences of the Paleocene-Eocene (P/E) Chouabine Formation in the Gafsa Basin (south western of Tunisia) in order to trace the sedimentological, climatic and oceanographic conditions. The REE chemistry and their distribution in the two archives are the same for each of the studied layers indicating that the coprolites and shark teeth experienced the same early diagenetic environments. However major differences occur between the Maastrichtian and the P/E reflecting changes in the depositional conditions. The Early Maastrichtian burial environment tended to be more anoxic with REE derived from reduced FeO. While in the P/E the REE patterns mimic the modern oxic-suboxic seawater, the REE source from remineralisation of organic coating could have more significance. The oxygen isotope compositions of the structural phosphates (delta O-18(PO4)) indicate a stable and warm climate during both studied time intervals. A small offset (-0.4 parts per thousand) in the delta O-18 value between the coprolites and shark teeth show minor thermal gradient between bottom and surface water. The pronounced negative shift of 34%. in delta C-13 values recorded in the upper part of the Chouabine Formation was ascribed to the Paleocene-Eocene boundary. At the same time the lack of negative change in the delta O-18 is explained by the semi-closed situation of the Gafsa Basin, which situation also played an important role in the evolution of the organic matters in the sediment resulting in the exceptional low delta C-13 values. (C) 2008 Elsevier B.V. All rights reserved.

Improved surgical technique for laparoscopic Roux-en-Y gastric bypass reduces complications at the gastrojejunostomy.

Roux-en-Y gastric bypass (RYGBP) is one of the most commonly performed bariatric procedures for morbidly obese patients. It is associated with effective long-term weight loss, but can lead to significant complications, especially at the gastrojejunostomy (GJS). All the patients undergoing laparoscopic RYGBP at one of our two institutions were included in this study. The prospectively collected data were reviewed retrospectively for the purpose of this study, in which we compared two different techniques for the construction of the GJS and their effects on the incidence of complications. In group A, anastomosis was performed on the posterior aspect of the gastric pouch. In group B, it was performed across the staple line used to form the gastric pouch. A 21-mm circular stapler was used in all patients. A total of 1,128 patients were included between June 1999 and September 2009-639 in group A and 488 in group B. Sixty patients developed a total of 65 complications at the GJS, with 14 (1.2%) leaks, 42 (3.7%) strictures, and 9 (0.8%) marginal ulcers. Leaks (0.2% versus 2%, p = 0.005) and strictures (0.8% versus 5.9%, p < 0.0001) were significantly fewer in group B than in group A. Improved surgical technique, as we propose, with the GJS across the staple line used to form the gastric pouch, significantly reduces the rate of anastomotic complications at the GJS. A circular 21-mm stapler can be used with a low complication rate, and especially a low stricture rate. Additional methods to limit complications at the GJS are probably not routinely warranted.

Pancreatic trauma in children.

We identified two distinct groups of patients in the 91 documented cases of pancreatic trauma (median age 8.0 years, range 0.6-15.8 years; M:F 2.5:1.0): 59 had a history of abdominal trauma and elevated serum lipase but no CT or ultrasound evidence of pancreatic injury (Group A); 32 had a history of abdominal trauma, elevated serum lipase but also had CT scan and/or ultrasound evidence of pancreatic injury (Group B). Patients with "less severe" injury based on normal imaging had a lower initial lipase level [Group A, median 651 U/L (interquartile range 520-1,324) vs. Group B, 1,608 U/L (interquartile range 680-3,526); p = 0.005] and shorter admission time [Group A, 9.0 days (interquartile range 5.5-15.5) vs. Group B, 13.4 days (interquartile range 6.8-23.8); p = 0.04]. There were no differences with respect to mortality (Group A, 13.5% vs. Group B, 12.5%), but patients with evidence of injury on imaging were more likely to have surgical intervention (p = 0.0001). The single most important overall cause of pancreatic trauma was involvement in a motor vehicle accident as a passenger or pedestrian. However, in children with high-grade ductal injury, bicycle handlebar injuries were most common. Associated injuries were common in both groups.

Replacement of (R)-methadone by a double dose of (R,S)-methadone in addicts: interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics.

METHODS: Twenty-two patients receiving (R)-methadone maintenance treatment were switched to a double dose of (R,S)-methadone: blood samples were collected before and after the change, and the concentrations of the enantiomers were measured. In the second period, during racemic methadone treatment, important interindividual variability in the stereoselective disposition of the enantiomers of methadone was measured, with (R)/(S) ratios ranging from 0.63 to 2.40. This point should be taken into account particularly with respect to therapeutic drug monitoring of racemic methadone. RESULTS: A significant decrease P < 0.005 in the mean serum concentration/dose ratios of the active (R)-enantiomer before and after the change was measured (mean 3.97 and 3.33). CONCLUSION: Although of small amplitude (16%), this decrease confirms previously described adaptive changes in methadone pharmacokinetics during racemic methadone maintenance treatment and may necessitate, in some patients, a dose adjustment.

Instrumental leadership: Measurement and extension of transformational-transactional leadership theory.

Leaders must scan the internal and external environment, chart strategic and task objectives, and provide performance feedback. These instrumental leadership (IL) functions go beyond the motivational and quid-pro quo leader behaviors that comprise the full-range-transformational, transactional, and laissez faire-leadership model. In four studies we examined the construct validity of IL. We found evidence for a four-factor IL model that was highly prototypical of good leadership. IL predicted top-level leader emergence controlling for the full-range factors, initiating structure, and consideration. It also explained unique variance in outcomes beyond the full-range factors; the effects of transformational leadership were vastly overstated when IL was omitted from the model. We discuss the importance of a "fuller full-range" leadership theory for theory and practice. We also showcase our methodological contributions regarding corrections for common method variance (i.e., endogeneity) bias using two-stage least squares (2SLS) regression and Monte Carlo split-sample designs.

Respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects

A survey was conducted in two pediatric intensive care units in hospitals in Porto Alegre, Brazil, in order to monitor the main respiratory viruses present in bronchiolitis and/or pneumonia and their involvement in the severity of viral respiratory infections. Viral respiratory infection prevalence was 38.7%. In bronchiolitis, respiratory syncytial virus (RSV) was detected in 36% of the cases. In pneumonia, the prevalence rates were similar for adenovirus (10.3%) and RSV (7.7%). There was a difference among the viruses detected in terms of frequency of clinical findings indicating greater severity. Frequency of crackles in patients with RSV (47.3%) showed a borderline significance (p = 0.055, Fisher's exact test) as compared to those with adenovirus (87.5%). The overall case fatality rate in this study was 2.7%, and adenovirus showed a significantly higher case fatality rate (25%) than RSV (2.8%) (p = 0.005). Injected antibiotics were used in 49% of the children with RSV and 60% of those with adenovirus. Adenovirus was not detected in any of the 33 children submitted to oxygen therapy.

Critical evaluation of outcome scales assessment of lateral ankle ligament reconstruction

Introduction: Les résultats d'une chirurgie du pied et de la cheville peuvent être évalués par des scores spécifiques à la région anatomique ainsi que par des scores spécifiques à la pathologie. Beaucoup de scores existent rendant la comparaison entre les études difficile. La présente étude se focalise sur une pathologie fréquente du pied et de la cheville et compare les résultats obtenu par deux scores spécifiques à la région et deux scores spécifiques à la pathologie. Méthode: Nous avons revu 41 patients ayant bénéficié d'une plastie ligamentaire externe de la cheville. Quatre scores ont été administrés simultanément: the Cumberland Ankle Instability Tool (CAIT) et the Chronic Ankle Instability Scale (CAIS), spécifiques à la pathologie, the American Orthopedic Foot & Ankle Society (AOFAS) hindfoot scale et the Foot and Ankle Ability Measure comprenant deux parties (FAAM1 et FAAM2), spécifiques à la région anatomique. Le degré de corrélation entre les scores a été évalué par le coefficient de corrélation de Pearson. L'analyse graphique des variances a été utilisée pour le choix de tests paramétriques versus non paramétriques. Des tests non paramétriques, le Kruskal-Wallis pour éliminer l'hypothèse nulle et le Mann-Whitney pour la comparaison entre les scores deux à deux, ont été utilisés. Résultats: Une différence significative (p<.005) a été démontrée entre le CAIS et l'AOFAS (p=.0002), entre le CAIS et le FAAM1 (p=.0001) et entre le CAIT et l'AOFAS (p=.0003) Conclusions: Cette étude compare les performances de quatre scores dont deux spécifiques à la région anatomique et deux spécifiques à la pathologie. Nous avons démontré une bonne corrélation entre les scores ainsi que des différences significatives entre les résultats obtenus par chacun d'eux. Les résultats obtenus par les scores spécifiques à la pathologie semblent être plus précis que ceux obtenus par les scores spécifiques à la région anatomique. De plus, nous avons mis en évidence une forte corrélation entre l'AOFAS et les autres scores. Le FAAM semble être un bon compromis car il offre la possibilité, du fait de ses deux parties, d'évaluer le résultat en fonction de la demande fonctionnelle du patient. Perspectives: Un algorithme est proposé qui permet d'évaluer la littérature spécifique de manière plus critique et peut s'adapter également à la recherche et à la clinique relative à d'autres pathologies du pied et de la cheville

High expectation in non-evidence-based smoking cessation interventions among smokers--the CoLaus study.

To assess the preferred methods to quit smoking among current smokers. Cross-sectional, population-based study conducted in Lausanne between 2003 and 2006 including 988 current smokers. Preference was assessed by questionnaire. Evidence-based (EB) methods were nicotine replacement, bupropion, physician or group consultations; non-EB-based methods were acupuncture, hypnosis and autogenic training. EB methods were frequently (physician consultation: 48%, 95% confidence interval (45-51); nicotine replacement therapy: 35% (32-38)) or rarely (bupropion and group consultations: 13% (11-15)) preferred by the participants. Non-EB methods were preferred by a third (acupuncture: 33% (30-36)), a quarter (hypnosis: 26% (23-29)) or a seventh (autogenic training: 13% (11-15)) of responders. On multivariate analysis, women preferred both EB and non-EB methods more frequently than men (odds ratio and 95% confidence interval: 1.46 (1.10-1.93) and 2.26 (1.72-2.96) for any EB and non-EB method, respectively). Preference for non-EB methods was higher among highly educated participants, while no such relationship was found for EB methods. Many smokers are unaware of the full variety of methods to quit smoking. Better information regarding these methods is necessary.

Use of quantum dots in aqueous solution to detect blood fingermarks on non-porous surfaces.

A new and original reagent based on the use of highly fluorescent cadmium telluride (CdTe) quantum dots (QDs) in aqueous solution is proposed to detect weak fingermarks in blood on non-porous surfaces. To assess the efficiency of this approach, comparisons were performed with one of the most efficient blood reagents on non-porous surfaces, Acid Yellow 7 (AY7). To this end, four non-porous surfaces were studied, i.e. glass, transparent polypropylene, black polyethylene, and aluminium foil. To evaluate the sensitivity of both reagents, sets of depleted fingermarks were prepared, using the same finger, initially soaked with blood, which was then successively applied on the same surface without recharging it with blood or latent secretions. The successive marks were then cut in halves and the halves treated separately with each reagent. The results showed that QDs were equally efficient to AY7 on glass, polyethylene and polypropylene surfaces, and were superior to AY7 on aluminium. The use of QDs in new, sensitive and highly efficient latent and blood mark detection techniques appears highly promising. Health and safety issues related to the use of cadmium are also discussed. It is suggested that applying QDs in aqueous solution (and not as a dry dusting powder) considerably lowers the toxicity risks.

Role of the transcriptional factor C/EBPbeta in free fatty acid-elicited beta-cell failure.

Fatty acids can favour the development of Type 2 diabetes by reducing insulin secretion and inducing apoptosis of pancreatic beta-cells. Here, we show that sustained exposure of the beta-cell line MIN6 or of isolated pancreatic islets to the most abundant circulating fatty acid palmitate increases the level of C/EBPbeta, an insulin transcriptional repressor. In contrast, two unsaturated fatty acids, oleate and linoleate were without effect. The induction of C/EBPbeta elicited by palmitate was prevented by inhibiting the ERK1/2 MAP kinase pathway or by reducing mitochondrial fatty acid oxidation with an inhibitor of Carnitine Palmitoyl Transferase-1. Overexpression of C/EBPbeta mimicked the detrimental effects of palmitate and resulted in a drastic reduction in insulin promoter activity, impairment in the capacity to respond to secretory stimuli and an increase in apoptosis. Our data suggest a potential involvement of C/EBPbeta as mediator of the deleterious effects of unsaturated free fatty acids on beta-cell function.

Red cell distribution width does not predict stroke severity or functional outcome.

INTRODUCTION: Red cell distribution width was recently identified as a predictor of cardiovascular and all-cause mortality in patients with previous stroke. Red cell distribution width is also higher in patients with stroke compared with those without. However, there are no data on the association of red cell distribution width, assessed during the acute phase of ischemic stroke, with stroke severity and functional outcome. In the present study, we sought to investigate this relationship and ascertain the main determinants of red cell distribution width in this population. METHODS: We used data from the Acute Stroke Registry and Analysis of Lausanne for patients between January 2003 and December 2008. Red cell distribution width was generated at admission by the Sysmex XE-2100 automated cell counter from ethylene diamine tetraacetic acid blood samples stored at room temperature until measurement. An χ(2) -test was performed to compare frequencies of categorical variables between different red cell distribution width quartiles, and one-way analysis of variance for continuous variables. The effect of red cell distribution width on severity and functional outcome was investigated in univariate and multivariate robust regression analysis. Level of significance was set at 95%. RESULTS: There were 1504 patients (72±15·76 years, 43·9% females) included in the analysis. Red cell distribution width was significantly associated to NIHSS (β-value=0·24, P=0·01) and functional outcome (odds ratio=10·73 for poor outcome, P<0·001) at univariate analysis but not multivariate. Prehospital Rankin score (β=0·19, P<0·001), serum creatinine (β=0·008, P<0·001), hemoglobin (β=-0·009, P<0·001), mean platelet volume (β=0·09, P<0·05), age (β=0·02, P<0·001), low ejection fraction (β=0·66, P<0·001) and antihypertensive treatment (β=0·32, P<0·001) were independent determinants of red cell distribution width. CONCLUSIONS: Red cell distribution width, assessed during the early phase of acute ischemic stroke, does not predict severity or functional outcome.