Impaired expression of the inducible cAMP early repressor accounts for sustained adipose CREB activity in obesity.

OBJECTIVEIncrease in adipose cAMP response binding protein (CREB) activity promotes adipocyte dysfunction and systemic insulin resistance in obese mice. This is achieved by increasing the expression of activating transcription factor 3 (ATF3). In this study we investigated whether impaired expression of the inducible cAMP early repressor (ICER), a transcriptional antagonist of CREB, is responsible for the increased CREB activity in adipocytes of obese mice and humans.RESEARCH DESIGN AND METHODSTotal RNA and nuclear proteins were prepared from visceral adipose tissue (VAT) of human nonobese or obese subjects, and white adipose tissue (WAT) of C57Bl6-Rj mice that were fed with normal or high-fat diet for 16 weeks. The expression of genes was monitored by real-time PCR, Western blotting, and electromobility shift assays. RNA interference was used to silence the expression of Icer.RESULTSThe expression of Icer/ICER was reduced in VAT and WAT of obese humans and mice, respectively. Diminution of Icer/ICER was restricted to adipocytes and was accompanied by a rise of Atf3/ATF3 and diminution of Adipoq/ADIPOQ and Glut4/GLUT4. Silencing the expression of Icer in 3T3-L1 adipocytes mimicked the results observed in human and mice cells and hampered glucose uptake, thus confirming the requirement of Icer for appropriate adipocyte function.CONCLUSIONSImpaired expression of ICER contributes to elevation in CREB target genes and, therefore, to the development of insulin resistance in obesity.

The effect of a smoking ban introduction to environmental tobacco smoke exposure in Swiss hospitality workers : Abstracts of the 23rd Annual Conference of the International Society of Environmental Epidemiology (ISEE), September 13-16, 2011, Barcelona, Spain

Background and Aims: To protect the population from environmental tobacco smoke (ETS) Switzerland introduced a nationwide rather heterogeneous smoking ban in May 2010. The exposure situation of non-smoking hospitality workers before and after implementation of the new law is being assessed in a prospective cohort study. Methods: Exposure to ETS was measured using a novel method developed by the Institute for Work and Health in Lausanne. It is a passive sampler called MoNIC (Monitor of NICotine). The nicotine of the ETS is fixed onto a filter and transformed into salt of not volatile nicotine. Subsequently the number of passively smoked cigarettes is calculated. Badges were placed at the workplace as well as distributed to the participants for personal measuring. Additionally a salivary sample was taken to determine nicotine concentration. Results: At baseline Spearman's correlation between workplace and personal badge was 0.47. The average cigarette equivalents per day at the workplace obtained by badge significantly dropped from 5.1 (95%- CI: 2.4 to 7.9) at baseline to 0.3 (0.2 to 0.4) at first follow-up (n=29) three months later (p<0.001). For personal badges the number of passively smoked cigarettes declined from 1.5 (2.7 to 0.4) per day to 0.5 (0.3 to 0.8) (n=16).Salivary nicotine concentration in a subset of 13 participants who had worked on the day prior to the examination was 2.63 ng/ml before and 1.53 ng/ml after the ban (p=0.04). Spearman's correlation of salivary nicotine was 0.56 with workplace badge and 0.79 with personal badge concentrations. Conclusions: Workplace measurements clearly reflect the smoking regulation in a venue. The MoNIC badge proves to be a sensitive measuring device to determine personal ETS exposure and it is a demonstrative measure for communication with lay audiences and study participants as the number of passively smoked cigarettes is an easily conceivable result.

Health for life : annual report of activities for the period January-December 2013

In Seychelles, cardiovascular diseases (CVD), notably stroke, ischemic heart disease and hypertensive heart disease has become the largest contributor of deaths (40%) in the entire population. CVD also results in a large burden of disability and also has subsequent social and economic impact. The Unit for Prevention and Control of Cardiovascular Diseases (UPCCD) provides leadership, expertise and capacity at national level for the surveillance, prevention and control of cardiovascular diseases through education, programs and input into policy.

A Multi-Center Phase II Study (SAKK 36/06) of Single Agent Everolimus (RAD001) In Patients with Relapsed or Refractory Mantle Cell Lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and remains incurable for most patients. Those who relapse after first line therapy or hematopoietic stem cell transplantation have a dismal prognosis with short response duration after salvage therapy. On a molecular level, MCL is characterised by the translocation t[11;14] leading to Cyclin D1 overexpression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) kinase and can be effectively blocked by mTOR inhibitors such as temsirolimus. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus (RAD001) in a prospective, multi-centre trial in patients with relapsed or refractory MCL (NCT00516412). The study was performed in collaboration with the EU-MCL network. Methods: Eligible patients with histologically/cytologically confirmed relapsed (not more than 3 prior lines of systemic treatment) or refractory MCL received everolimus 10 mg orally daily on day 1 - 28 of each cycle (4 weeks) for 6 cycles or until disease progression. The primary endpoint was the best objective response with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints. A response rate of 10% was considered uninteresting and, conversely, promising if 30%. The required sample size was 35 pts using the Simon's optimal two-stage design with 90% power and 5% significance. Results: A total of 36 patients with 35 evaluable patients from 19 centers were enrolled between August 2007 and January 2010. The median age was 69.4 years (range 40.1 to 84.9 years), with 22 males and 13 females. Thirty patients presented with relapsed and 5 with refractory MCL with a median of two prior therapies. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade III or higher. Eighteen patients received 6 or more cycles of everolimus treatment. The objective response rate was 20% (95% CI: 8-37%) with 2 CR, 5 PR, 17 SD, and 11 PD. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Conclusion: This study demonstrates that single agent everolimus 10 mg once daily orally is well tolerated. The null hypothesis of inactivity could be rejected indicating a moderate anti-lymphoma activity in relapsed/refractory MCL. Further studies of either everolimus in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL.

Meeting highlights of the 8th Annual Scientific Sessions of the Society For Cardiovascular Magnetic Resonance, January 21 to 23, 2005.

Parallel tracks for clinical scientists, basic scientists, and pediatric imagers was the novel approach taken for the highly successful 8th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance, held in San Francisco, California, January 21 to 23, 2005. Attendees were immersed in information on the latest scientific advances in cardiovascular magnetic resonance (CMR) from mice to man and technological advances from systems with field strengths from 0.5 T to 11.7 T. State-of-the-art applications were reviewed, spanning a wide range from molecular imaging to predicting outcome with CMR in large patient populations.

Annual Review of the European Football Players' Labour Market / Etude annuelle du marché du travail européen des footballeurs

The key reference on the labour market and the logics of squad formation in the big-5 European leagues. One hundred richly coloured pages, illustrated by graphics, maps, rankings, statistical models and analysis in French and English which inform managers about potential strategies to put their clubs on the road to success help managers of federations and players' unions to understand current trends and to take decisions ... suggest to journalists new lines of investigation likely to interest the general public allow researchers and students to benefit from reliable and comparable sources, developed with the greatest possible rigour ... give fans the possibility to understand in detail the dynamics at work in their favourite sport and club.

A Multi-Center Phase II Study (SAKK 36/06) of Single Agent Everolimus (RAD001) In Patients with Relapsed or Refractory Mantle Cell Lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and remains incurable for most patients. Those who relapse after first line therapy or hematopoietic stem cell transplantation have a dismal prognosis with short response duration after salvage therapy. On a molecular level, MCL is characterised by the translocation t[11;14] leading to Cyclin D1 overexpression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) kinase and can be effectively blocked by mTOR inhibitors such as temsirolimus. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus (RAD001) in a prospective, multi-centre trial in patients with relapsed or refractory MCL (NCT00516412). The study was performed in collaboration with the EU-MCL network. Methods: Eligible patients with histologically/cytologically confirmed relapsed (not more than 3 prior lines of systemic treatment) or refractory MCL received everolimus 10 mg orally daily on day 1 - 28 of each cycle (4 weeks) for 6 cycles or until disease progression. The primary endpoint was the best objective response with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints. A response rate of ≤ 10% was considered uninteresting and, conversely, promising if ≥ 30%. The required sample size was 35 pts using the Simon's optimal two-stage design with 90% power and 5% significance. Results: A total of 36 patients with 35 evaluable patients from 19 centers were enrolled between August 2007 and January 2010. The median age was 69.4 years (range 40.1 to 84.9 years), with 22 males and 13 females. Thirty patients presented with relapsed and 5 with refractory MCL with a median of two prior therapies. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade III or higher. Eighteen patients received 6 or more cycles of everolimus treatment. The objective response rate was 20% (95% CI: 8-37%) with 2 CR, 5 PR, 17 SD, and 11 PD. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Conclusion: This study demonstrates that single agent everolimus 10 mg once daily orally is well tolerated. The null hypothesis of inactivity could be rejected indicating a moderate anti-lymphoma activity in relapsed/refractory MCL. Further studies of either everolimus in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL.