Everolimus-eluting bioresorbable stent vs. durable polymer everolimus-eluting metallic stent in patients with ST-segment elevation myocardial infarction: results of the randomized ABSORB ST-segment elevation myocardial infarction-TROFI II trial.

AIMS Patients with ST-segment elevation myocardial infarction (STEMI) feature thrombus-rich lesions with large necrotic core, which are usually associated with delayed arterial healing and impaired stent-related outcomes. The use of bioresorbable vascular scaffolds (Absorb) has the potential to overcome these limitations owing to restoration of native vessel lumen and physiology at long term. The purpose of this randomized trial was to compare the arterial healing response at short term, as a surrogate for safety and efficacy, between the Absorb and the metallic everolimus-eluting stent (EES) in patients with STEMI. METHODS AND RESULTS ABSORB-STEMI TROFI II was a multicentre, single-blind, non-inferiority, randomized controlled trial. Patients with STEMI who underwent primary percutaneous coronary intervention were randomly allocated 1:1 to treatment with the Absorb or EES. The primary endpoint was the 6-month optical frequency domain imaging healing score (HS) based on the presence of uncovered and/or malapposed stent struts and intraluminal filling defects. Main secondary endpoint included the device-oriented composite endpoint (DOCE) according to the Academic Research Consortium definition. Between 06 January 2014 and 21 September 2014, 191 patients (Absorb [n = 95] or EES [n = 96]; mean age 58.6 years old; 17.8% females) were enrolled at eight centres. At 6 months, HS was lower in the Absorb arm when compared with EES arm [1.74 (2.39) vs. 2.80 (4.44); difference (90% CI) -1.06 (-1.96, -0.16); Pnon-inferiority <0.001]. Device-oriented composite endpoint was also comparably low between groups (1.1% Absorb vs. 0% EES). One case of definite subacute stent thrombosis occurred in the Absorb arm (1.1% vs. 0% EES; P = ns). CONCLUSION Stenting of culprit lesions with Absorb in the setting of STEMI resulted in a nearly complete arterial healing which was comparable with that of metallic EES at 6 months. These findings provide the basis for further exploration in clinically oriented outcome trials.

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.

Diagnosis and therapy of retained fetal membranes, puerperal metritis and clinical endometritis in cattle: Results of the Online-survey among Swiss practitioners. II. Puerperal metritis and clinical endometritis

The aim of the study was to obtain the diagnostic and therapeutic approach among Swiss practitioners in cows with puerperal metritis and clinical endometritis (part 2). All members of the Association for ruminant health were contacted per email via the newsletter. The survey was completed by 128 veterinarians, partially responded by 140 veterinarians. The following main symptoms of puerperal metritis were stated by the practitioners: purulent vaginal discharge, fever and reduced appetite. A vaginal and rectal examination was performed to diagnose the disease. Usually, an intrauterine treatment with tetracycline or cefapirin was done. Parenteral administration of tetracycline or penicillin was often combined with PGF(2α), NSAIDS or cortisone. Clinical endometritis was also diagnosed by vaginal and rectal examination and the main symptom indicated was purulent vaginal discharge. The therapy consisted of the administration of PGF(2α), uterine infusions predominantly with cefapirin, and rarely with parenteral administration of antibiotics. Further diagnostic tools were not used and normally cows were not rechecked. The success of the therapy of puerperal metritis and clinical endometritis was judged to be satisfactory to excellent.

Organisation of the equine immunoglobulin constant heavy chain genes. II. Equine cgamma genes.

The number of immunoglobulin G constant heavy chain genes (cgamma genes) varies broadly among mammalian species, reflecting structural and functional differences between expressed immunoglobulin G (IgG) isotypes and allotypes. Up to now equine IgG isotypes have been defined only at the biochemical and serological level. It is still not clear how many IgG isotypes exist in horses and whether there are any allotypes. Here, we describe the isolation and characterisation of equine cgamma genes. An equine genomic lambda phage library was screened with a human cgamma4 probe. Cross-hybridising equine cgamma sequences were cloned twice and characterised by restriction mapping with the human cgamma4 and a murine sgamma1 probe. Genomic equine DNA probes for both, cgamma genes and corresponding switch regions (sgamma), were isolated and used for a more detailed BamHI restriction analysis, comparing genomic DNA of various horses. This analysis reveals the existence of at least five, or probably six cgamma genes in the equine haploid genome. Beside the porcine system, this is the highest number of cgamma genes described for any mammalian species. Moreover, for two of these cgamma genes, BamHI restriction fragment length polymorphism became evident.

CHARACTERIZATION OF THE COLONIZATION FACTOR ANTIGEN II PLASMID (CFA/II) FROM ENTEROTOXIGENIC ESCHERICHIA COLI

The etiological role of enterotoxigenic E. coli (ETEC) in diarrheal diseases of man and domestic animals is firmly established. Besides the production of enterotoxins (ST and LT), ETEC produces other important virulence factors; the colonization factor antigens (CFAs). CFAs mediate the attachment of ETEC to the epithelial cells of the small intestine, and this favors colonization by the bacteria and facilitates delivery of the enterotoxins to the intestinal cells.^ The production of enterotoxin and CFA is determined by plasmids and has been found to be restricted to a select number of E. coli serotypes.^ In this work, plasmid DNA analysis was performed in twenty-three CFA/II-producing enterotoxigenic Escherichia coli strains and their spontaneous CFA/II-negative derivatives. In some cases, strains lost the high molecular weight plasmid and also the ability to produce CFA/II, ST and LT. In other cases there was a deletion of the plasmid, which produced strains that were CFA/II('-), ST('-), LT('-) or CFA/II('-), ST('+), LT('+).^ The CFA/II plasmid from strain PB-176 (06:H16:CFA/II('+), ST('+), LT('+)) was transferred by transformation into E. coli K12 with concomitant transfer of the three characteristics: CFA/II, ST and LT.^ A physical map of the prototype CFA/II:ST:LT (pMEP60) plasmid was constructed by restriction endonuclease analysis and compared to plasmids from three other CFA/II-producing strains. A CFA/II-negative (but ST and LT positive) deletion derivative of pMEP60 (pMEP30) was also included in the map. The four CFA/II plasmids analyzed had a common region of approximately 30 kilobase pairs. The toxin genes were approximately 5 kbp apart and about 20 kbp from the common region. The information given by this physical map could be of great value when constructing a clone that will express the CFA/II genes but not the toxin genes. ^

Variational Calculation of the Hydrogen Molecular Cation using Maple (II). The pi and pi-star Orbitals

The pi and pi-star orbitals of the hydrogen molecular cation are obtained using Maple in the same manner as the sigma and sigma-star orbitals were obtained in paper-36.

Violet Cameron, Szenenfoto, Kniestück, in: Alfred Cellier: The sultan of Mocha

Signatur des Originals: S 36/F08351

Elizabeth Bannister als Patty, George Mattocks als Lord Aimworth, Szenenfoto, Doppelbildnis, in: Samuel Arnold: The Maid of the Mill, II. Akt, 3. Szene : Patty: "Cease, oh cease, to overwhelm me"

Signatur des Originals: S 36/G00065

Structural determinants of subunit -subunit interactions and subcellular localization of the calcium /calmodulin -dependent protein kinase II

The multifunctional Ca$\sp{2+}$/calmodulin-dependent protein kinase II (CaM kinase) is a Ser/Thr directed protein kinase that participates in diverse Ca$\sp{2+}$ signaling pathways in neurons. The function of CaM kinase depends upon the ability of subunits to form oligomers and to interact with other proteins. Oligomerization is required for autophosphorylation which produces significant functional changes that include Ca$\sp{2+}$/calmodulin-independent activity and calmodulin trapping. Associations with other proteins localize CaM kinase to specific substrates and effectors which serves to optimize the efficiency and speed of signal transduction. In this thesis, we investigate the interactions that underlie the appropriate positioning of CaM kinase activity in cells. We demonstrate that the subcellular distribution of CaM kinase is dynamic in hippocampal slices exposed to anoxic/aglycemic insults and to high K$\sp{+}$-induced depolarization. We determine the localization of CaM kinase domains expressed in neurons and PC-12 cells and find that the C-terminal domain of the $\alpha$ subunit is necessary for localization to dendrites. Moreover, monomeric forms of the enzyme gain access to the nucleus. Attempts made to identify novel CaM kinase binding proteins using the yeast two-hybrid system resulted in the isolation of hundreds of positive clones. Those that have been sequenced are identical to CaM kinase isoforms. Finally, we report the discovery of specific regions within the C-terminal domain that are necessary and sufficient for subunit-subunit interactions. Differences between the $\alpha$ and $\beta$ isoforms were discovered that indicate unique structural requirements for oligomerization. A model for how CaM kinase subunits interact to form holoenzymes and how structural heterogeneity might influence CaM kinase function is presented. ^