Favorable Effect of Anti-TNF Therapy on Insulin Sensitivity in Nonobese, Nondiabetic Patients with Inflammatory Bowel Disease

Background. The aim of this study was to investigate the effect of anti-TNF therapy on glucose and lipid metabolism in nondiabetic, nonobese patients with inflammatory bowel disease (IBD). Patients and Methods. We studied 44 patients with IBD, without a known history of diabetes. Three of the patients were diagnosed with overt diabetes and were excluded. Eighteen of the remaining patients (9 M/9 F, 33.6 ± 8.8 years) were on anti-TNF therapy for longer than 1 year, while 23 patients (16 M/7 F, 38.7 ± 12.5 years) were treated with aminosalicylates (AMSs). Twelve of the patients from the second group were then treated with anti-TNF and reassessed 6 months later. Fasting glucose, insulin, c-peptide, HbA1c, lipid, CRP, and fibrinogen levels were determined, and HOMA-IR index was calculated in all patients. Results. Patients from the two therapy groups were matched for age and BMI and were not obese. We did not find any differences between patients from the two therapy groups regarding fasting glucose, c-peptide, HbA1c, total cholesterol, HDL, LDL, triglycerides, CRP, and HOMA-IR index. In patients who were treated for 6 months with anti-TNF, a statistically significant decrease in insulin (before 15.5 ± 5.9 versus after 9.9 ± 2.9 μIU/ml, p=0.042) and c-peptide (before 2.4 ± 1 versus after 1.3 ± 0.4 ng/ml, p=0.030) levels as well as the HOMA-IR index (before 4.2 ± 1.9 versus after 2.2 ± 0.9, p=0.045) was observed, without any changes in weight, BMI, glucose, HbA1c, lipid, CRP, and fibrinogen levels. Conclusion. Anti-TNF therapy exerts a favorable effect on insulin sensitivity, while it has no effect on lipid levels in nondiabetic, nonobese patients with inflammatory bowel disease

Development of a Chromosomally Integrated Metabolite-Inducible Leu3p-α-IPM “Off-On” Gene Switch

Background: Present technology uses mostly chimeric proteins as regulators and hormones or antibiotics as signals to induce spatial and temporal gene expression. Methodology/Principal Findings: Here, we show that a chromosomally integrated yeast ‘Leu3p-a-IRM ’ system constitutes a ligand-inducible regulatory ‘‘off-on’ ’ genetic switch with an extensively dynamic action area. We find that Leu3p acts as an active transcriptional repressor in the absence and as an activator in the presence of a-isopropylmalate (a-IRM) in primary fibroblasts isolated from double transgenic mouse embryos bearing ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence of the branched amino acid biosynthetic pathway in animals, metabolically stable a-IPM presents an EC 50 equal to 0.8837 mM and fast ‘‘OFF-ON’ ’ kinetics (t 50ON = 43 min, t 50OFF = 2.18 h), it enters the cells via passive diffusion, while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex vivo. Conclusions/Significance: Our results demonstrate that the ‘Leu3p-a-IRM ’ constitutes a simpler and safer system for inducible gene expression in biomedical applications

A qualitative analysis exploring preferred methods of peer support to encourage adherence to a Mediterranean diet in a Northern European population at high risk of cardiovascular disease.

BACKGROUND: Epidemiological and randomised controlled trial evidence demonstrates that adherence to a Mediterranean diet (MD) can reduce cardiovascular disease (CVD) risk. However, methods used to support dietary change have been intensive and expensive. Peer support has been suggested as a possible cost-effective method to encourage adherence to a MD in at risk populations, although development of such a programme has not been explored. The purpose of this study was to use mixed-methods to determine the preferred peer support approach to encourage adherence to a MD. METHODS: Qualitative (focus groups) and quantitative methods (questionnaire and preference scoring sheet) were used to determine preferred methods of peer support. Sixty-seven high CVD risk participants took part in 12 focus groups (60% female, mean age 64 years) and completed a questionnaire and preference scoring sheet. Focus group data were transcribed and thematically analysed. RESULTS: The mean preference score (1 being most preferred and 5 being least preferred) for group support was 1.5, compared to 3.4 for peer mentorship, 4.0 for telephone peer support and 4.0 for internet peer support. Three key themes were identified from the transcripts: 1. Components of an effective peer support group: discussions around group peer support were predominantly positive. It was suggested that an effective group develops from people who consider themselves similar to each other meeting face-to-face, leading to the development of a group identity that embraces trust and honesty. 2. Catalysing Motivation: participants discussed that a group peer support model could facilitate interpersonal motivations including encouragement, competitiveness and accountability. 3. Stepping Stones of Change: participants conceptualised change as a process, and discussed that, throughout the process, different models of peer support might be more or less useful. CONCLUSION: A group-based approach was the preferred method of peer support to encourage a population at high risk of CVD to adhere to a MD. This finding should be recognised in the development of interventions to encourage adoption of a MD in a Northern European population

Multi-informant validity evidence for the SSIS SEL Brief Scales across six European countries

The SSIS SEL Brief Scales (SSIS SELb) are multi-informant (teacher, parent, and student) measures that were developed to efficiently assess the SEL competencies of school-age youth in the United States. Recently, the SSIS SELb was translated into multiple languages for use in a multi- site study across six European countries (Croatia, Greece, Italy, Latvia, Portugal, and Romania). The purpose of the current study was to examine concurrent and predictive evidence for the SEL Composite scores from the translated versions of the SSIS SELb Scales. Results indicated that SSIS SELb Composite scores demonstrated expected positive concurrent and predictive relationships with scores from the Connor-Davidson Resilience Scale (CD-RISC) and negative relationships with scores from the problem behavior scales of the Strengths and Difficulties Questionnaire (SDQ). Although there were a few exceptions, these patterns generally were consistent across informants (parents, teachers, and students) and samples providing initial validity evidence for the Composite score from the translated versions of the SSIS SELb Scales. Limitations and future research directions are discussed.peer-reviewe

Evidence-Based PET for Abdominal and Pelvic Tumours

Evidence-based data about the usefulness of positron emission tomography (PET) and hybrid imaging methods (PET/CT and PET/MRI) in abdominal and pelvic tumours have been collected and discussed in this chapter. These data were divided in three sections: (1) gastrointestinal tumours, (2) uro-genital tumours, (3) gynaecological tumours. Several pooled data (diagnostic and prognostic data), clinical settings (e.g. staging, restaging, treatment evaluation) and radiotracers as fluorine-18 fluorodeoxyglucose (18F-FDG), radiolabelled choline and prostate-specific membrane antigen (PSMA) were considered

Inhibitor-based methods for the detection of KPC carbapenemase- producing Enterobacteriaceae in clinical practice by using boronic acid compounds

Enterobacteriaceae clinical strains that produce the class A carbapenem-hydrolysing enzyme KPC (Klebsiella pneumoniae carbapenemase) are increasingly reported worldwide, and are already endemic in North and South America, China, Israel and Greece. The accurate detection of KPC enzymes is of utmost importance for containing the global spread of KPC producers. Currently, the detection of putative carbapenemase production is based on an initial phenotypic screen for carbapenem resistance followed by the modified Hodge test (MHT) as a confirmatory test. However, the MHT is often difficult to interpret, is not specific for carbapenemase activity due to KPC and there are reports of false-positive results with CTX-M-positive or AmpC-hyper-producing Enterobacteriaceae. Boronic acid compounds are serine-type β-lactamase inhibitors that were employed originally for the detection of class C plasmidic AmpCs in Enterobacteriaceae. Recently, they have also been evaluated for the differentiation of KPC-producing Enterobacteriaceae. In that respect, combined-disc tests using carbapenems with and without phenylboronic acid (PBA) have been proposed as the most accurate phenotypic tests for detecting KPC production. When these disc tests are extended to include carbapenem discs with EDTA or both PBA and EDTA on the same plate, the production of metallo-β-lactamase (MBL) or both KPC and MBL, respectively, can also be accurately detected. Phenotypic tests based on the inhibitory activity of boronic acid compounds are very easy to perform and interpret, and may be applied from the first day of isolation of the suspected resistant Enterobacteriaceae. We think that they could effectively replace MHT for the convenient and early detection of KPC carbapenemases in regions where these enzymes are common. © The Author 2010

Thrombosis in paroxysmal nocturnal hemoglobinuria at a glance: a clinical review.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired stem cell disorder, with its primary clinical manifestations being hemolytic anemia, marrow failure and thrombophilia. Chronic hemolysis, failures of the fibrinolytic system, increased leukocyte-derived tissue factor levels in plasma, procoagulant microparticles generated through complement-mediated damage of platelets and venous endothelium are related to the acquired hypercoagulable state. Visceral thrombosis (including hepatic veins and mesenteric veins), cerebrovascular events and pulmonary embolism predict a poor outcome. Thrombosis is also associated with significant morbidity during pregnancy. Depending on the sites of thrombosis, a score-based probability to predict outcome can be assigned. Abdominal vein thromboses account for the majority of morbidity and mortality related to thrombosis, and time-dependent trends suggest that mortality rates tend to decline, with the advent of evolution of therapeutic and diagnostic strategies. In contrast, mortality rates from cerebrovascular events display no significant decline. Prompt diagnosis requires both clinical suspicion and sophisticated imaging techniques, along with multidisciplinary therapeutic intervention. In the eculizumab era, a significant reduction of thrombotic events was observed during therapy, and long-term follow up is needed to establish any benefit in rates and pattern of this complication. However, up to now, only bone marrow transplantation permanently abolishes the coagulation defect

Escherichia hermannii as the sole isolate from a patient with purulent conjunctivitis

Escherichia hermannii was isolated in pure culture from a patient with acute purulent conjunctivitis after a minor ocular injury. This is the first report of E. hermannii isolated as the sole pathogen from an infected site without prior antibiotic exposure, confirming the pathogenic potential of the microorganism. Copyright © 2008, American Society for Microbiology. All Rights Reserved