Alterations in content and localization of defensins in rat ileum and jejunum following ischemia-reperfusion. Specific peptides, in specific places, for specific jobs?

Objective: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. Methods: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular location of antimicrobials. Results: Ischemia-reperfusion increased neutrophil defensin alpha (RNP-1) in jejunum; rat beta defensin 1 was increased 2-fold in ileal mucosa and slightly reduced in jejunal mucosa; rat beta defensin 2 was reduced by ischemia-reperfusion in ileum, but slightly increased in jejunum; rat beta defensin 3 was concentrated in the muscularis externa and myenteric plexus of the jejunum; ischemia-reperfusion did not alter cathelicidin LL-37 content in the small intestine, although a greater concentration was seen in jejunum compared with ileum. Conclusion: Ischemia-reperfusion injury caused changes in antimicrobial content in defined areas, and these different regulations might reflect the specific roles of jejunum versus ileum.

Energy beverages: content and safety.

Exercise is making a resurgence in many countries, given its benefits for fitness as well as prevention of obesity. This trend has spawned many supplements that purport to aid performance, muscle growth, and recovery. Initially, sports drinks were developed to provide electrolyte and carbohydrate replacement. Subsequently, energy beverages (EBs) containing stimulants and additives have appeared in most gyms and grocery stores and are being used increasingly by "weekend warriors" and those seeking an edge in an endurance event. Long-term exposure to the various components of EBs may result in significant alterations in the cardiovascular system, and the safety of EBs has not been fully established. For this review, we searched the MEDLINE and EMBASE databases from 1976 through May 2010, using the following keywords: energy beverage, energy drink, power drink, exercise, caffeine, red bull, bitter orange, glucose, ginseng, guarana, and taurine. Evidence regarding the effects of EBs is summarized, and practical recommendations are made to help in answering the patient who asks, "Is it safe for me to drink an energy beverage when I exercise?"

The Design of International Trade Agreements: Introducing a New Dataset

Preferential trade agreements (PTAs) have been proliferating for the last twenty years. A large literature has studied various aspects of this phenomenon. Until recently, however, many large-N studies have paid only scant attention to variation across PTAs in terms of content and design. Our contribution to this literature is a new dataset on the design of trade agreements that is the most comprehensive in terms of both variables coded and agreements covered. We illustrate the dataset’s usefulness in re-visiting the questions if and to what extent PTAs impact trade flows. The analysis shows that on average PTAs increase trade flows, but that this effect is largely driven by deep agreements. In addition, we provide evidence that provisions that tackle behind-the-border regulation matter for trade flows. The dataset’s contribution is not limited to the PTA literature, however. Broader debates on topics such as institutional design and the legalization of international relations will also benefit from the novel data.

Individual Video Training iVT and Annotating Academic Videos AAV: two complementing technologies

Individual Video Training iVT and Annotating Academic Videos AAV: two complementing technologies 1. Recording communication skills training sessions and reviewing them by oneself, with peers, and with tutors has become standard in medical education. Increasing numbers of students paired with restrictions of financial and human resources create a big obstacle to this important teaching method. 2. Everybody who wants to increase efficiency and effectiveness of communication training can get new ideas from our technical solution. 3. Our goal was to increase the effectiveness of communication skills training by supporting self, peer and tutor assessment over the Internet. Two technologies of SWITCH, the national foundation to support IT solutions for Swiss universities, came handy for our project. The first is the authentication and authorization infrastructure providing all Swiss students with a nationwide single login. The second is SWITCHcast which allows automated recording, upload and publication of videos in the Internet. Students start the recording system by entering their single login. This automatically links the video with their password. Within a few hours, they find their video password protected on the Internet. They now can give access to peers and tutors. Additionally, an annotation interface was developed. This software has free text as well as checklist annotations capabilities. Tutors as well as students can create checklists. Tutor’s checklists are not editable by students. Annotations are linked to tracks. Tracks can be private or public. Public means visible to all who have access to the video. Annotation data can be exported for statistical evaluation. 4. The system was well received by students and tutors. Big numbers of videos were processed simultaneously without any problems. 5. iVT http://www.switch.ch/aaa/projects/detail/UNIBE.7 AAV http://www.switch.ch/aaa/projects/detail/ETHZ.9

Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial

Background Biodegradable polymers for release of antiproliferative drugs from metallic drug-eluting stents (DES) aim to improve long-term vascular healing and efficacy. We designed a large scale clinical trial to compare a novel thin strut, cobalt chromium DES with silicon carbide coating releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) with the durable polymer-based Xience Prime everolimus-eluting stent (X-EES) in an all-comers patient population. Design The multicenter BIOSCIENCE trial (NCT01443104) randomly assigned 2,119 patients to treatment with biodegradable polymer SES or durable polymer EES at 9 sites in Switzerland. Patients with chronic stable coronary artery disease or acute coronary syndromes, including non-ST-elevation and ST-elevation myocardial infarction, were eligible for the trial if they had at least one lesion with a diameter stenosis >50% appropriate for coronary stent implantation. The primary endpoint target lesion failure (TLF) is a composite of cardiac death, target-vessel myocardial infarction, and clinically-driven target lesion revascularization within 12 months. Assuming a TLF rate of 8% at 12 months in both treatment arms and accepting 3.5% as a margin for non-inferiority, inclusion of 2,060 patients would provide 80% power to detect non-inferiority of the biodegradable polymer SES compared with the durable polymer EES at a one-sided type I error of 0.05. Clinical follow-up will be continued through five years. Conclusion The BIOSCIENCE trial will determine whether the biodegradable polymer SES is non-inferior to the durable polymer EES with respect to TLF.

Ideas of God in Israel : their content and development

Edward Pace

Comprehensive geriatric assessment in patients undergoing transcatheter aortic valve implantation–rationale and design of the European CGA-TAVI registry

Abstract Purpose Aortic stenosis (AS) is the most common valvular abnormality in the elderly population. For inoperable patients or those at high-risk for surgery, transcatheter aortic valve implantation (TAVI) has become an alternative therapeutic option. The aim of the “Comprehensive geriatric assessment for transcatheter aortic valve implantation” (CGA-TAVI) registry is to evaluate the effectiveness of TAVI from the perspective of the geriatrician and to identify patient characteristics and indicators related to complications and clinical benefits for patients with symptomatic severe calcified degenerative AS undergoing TAVI. Materials and methods The CGA-TAVI registry is an international, multi-center, prospective, observational registry across Europe with consecutive patient enrolment. The registry will enrol up to 200 patients with AS undergoing TAVI, starting August 2013. CGA-TAVI has two co-primary objectives: (1) Establish predictive value of Comprehensive geriatric assessment (CGA) for mortality and/or hospitalization in TAVI patients. (2) Demonstrate CGA changes within 3 months after TAVI. Secondary objectives are: (1) Establish predictive value of CGA in TAVI patients for all-cause hospitalization, TAVI-related hospitalization, and nursing home admission. (2) Develop a comprehensive score for the assessment of TAVI patient prognosis. Conclusions The data obtained from the CGA-TAVI registry will supplement previous results to document the potential value of the effectiveness of TAVI from the perspective of geriatricians and will allow the assessment of the predictive value of CGA for mortality and/or hospitalization in elderly TAVI patients. Keywords Aortic stenosis; Transcatheter aortic valve implantation (TAVI); Comprehensive geriatric assessment (CGA); Registry; Predictor

Exercise efficiency relates with mitochondrial content and function in older adults

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty-eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1-h submaximal test (55% V˙O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with (31)P-MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial

AIMS The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes. METHODS AND RESULTS Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. CONCLUSIONS The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Arterial healing following primary PCI using the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) versus the durable polymer everolimus-eluting metallic stent (XIENCE) in patients with acute ST-elevation myocardial infarction: rationale and design of the randomised TROFI II study

AIMS The Absorb bioresorbable vascular scaffold (Absorb BVS) provides similar clinical outcomes compared with a durable polymer-based everolimus-eluting metallic stent (EES) in stable coronary artery disease patients. ST-elevation myocardial infarction (STEMI) lesions have been associated with delayed arterial healing and impaired stent-related outcomes. The purpose of the present study is to compare directly the arterial healing response, angiographic efficacy and clinical outcomes between the Absorb BVS and metallic EES. METHODS AND RESULTS A total of 191 patients with acute STEMI were randomly allocated to treatment with the Absorb BVS or a metallic EES 1:1. The primary endpoint is the neointimal healing (NIH) score, which is calculated based on a score taking into consideration the presence of uncovered and malapposed stent struts, intraluminal filling defects and excessive neointimal proliferation, as detected by optical frequency domain imaging (OFDI) six months after the index procedure. The study will provide 90% power to show non-inferiority of the Absorb BVS compared with the EES. CONCLUSIONS This will be the first randomised study investigating the arterial healing response following implantation of the Absorb BVS compared with the EES. The healing response assessed by a novel NIH score in conjunction with results on angiographic efficacy parameters and device-oriented events will elucidate disease-specific applications of bioresorbable scaffolds.