Bleeding risk of antiplatelet drugs compared with oral anticoagulants in older patients with atrial fibrillation: a systematic review and meta-analysis.

Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted. SUMMARY: Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.

The Evolution of HD2 Proteins in Green Plants.

In eukaryotes, protein deacetylation is carried out by two well-conserved histone deacetylase (HDAC) families: RPD3/HDA1 and SIR2. Intriguingly, model plants such as Arabidopsis express an additional plant-specific HDAC family, termed type-2 HDACs (HD2s). Transcriptomic analyses from more than 1300 green plants generated by the 1000 plants (1KP) consortium showed that HD2s appeared early in green plant evolution, the first members being detected in several streptophyte green alga. The HD2 family has expanded via several rounds of successive duplication; members are expressed in all major green plant clades. Interestingly, angiosperm species express new HD2 genes devoid of a zinc-finger domain, one of the main structural features of HD2s. These variants may have been associated with the origin and/or the biology of the ovule/seed.

[Study of cytokines content and gangliosides metabolism at experimental brain edema].

The content of cytokines, and gangliosides metabolism, and the quantity of lipid peroxidation products were studied at experimental brain edema. Data obtained show increase the level of proinflammatory cytokins and decrease the level of antiinflammatory cytokines during development of brain edema. Along with this we reveal the accumulation of lipid peroxidation products (diene conjugates, hydroperoxides, and malonic dialdehyde). Each fraction of gangliosides decreased, but the product of their hydrolytic dissociation sphingosine increased at experimental brain edema.

[Neutral and acid glycolipids in the brain in the presence of ischemia and during antioxidant treatment].

The content of lipid peroxidation products and the metabolism of gangliosides and galactosylceramides in brain tissue were studied in the presence of ischemia and when an agent containing nicotinic acid and cysteine is administered. The above agent was found to have an antioxidative effect that was evident in the lower levels of lipid peroxides and in the normalized qualitative and quantitative content of galactosylceramides and gangliosides.

[Shift in the content of immune cytokines in heart of mice under acoustic stress conditions and delta-sleep inducing peptide application].

Quantitative shifts in the content of interleukine-1, -2 and -6 of the myocardium of mice under the conditions of acoustic stress and delta-sleep inducing peptide action are studied. It has been shown that injection of delta-sleep inducing peptide has no effect on the level of interleukine-1 and -2 in the myocardial tissue, whereas the quantity of interleukine-6 increased. The level of interleukine-1- and -6 in the myocardium were increased and no significant changes were observed in the level of interleukine-2 under the noise action. Interleukine-1- and -2 were not detected in the hypophysis of experimental animals of all groups (intact, under acoustic stress, under delta-sleep inducing peptide application). The level of interleukine-6 in the hypothalamus decreased under conditions of acoustic stress, whereas administration of delta-sleep inducing peptide has no effect on its level. The obtained data are considered in the context of immune modulating properties of delta-sleep inducing peptide.

Postgraduate year does not influence operating time in laparoscopic cholecystectomy.

BACKGROUND: Surgical resident education may contribute to increased operating time, thus increasing costs at teaching institutions. It is possible that junior residents, in particular, with less experience could contribute to longer operating times for laparoscopic cholecystectomy. We hypothesized that all general surgery residents, regardless of level of training and with proper supervision, could complete a laparoscopic cholecystectomy in a safe and timely fashion. MATERIALS AND METHODS: A retrospective study was performed using data collected from laparoscopic cholecystectomies completed under the supervision of one attending surgeon over a 2-year period. Operating times were recorded, the operating surgeon was identified, and cases were assigned an acuity level based on pathologic findings. Operative times were compared after dividing surgeons into three groups (junior residents, senior residents, and staff). RESULTS: Seventy-one cases were entered into the study. There were no differences when comparing mean operating times among the three groups (P = 0.2, analysis of variance). The pathologic acuity in each group was similar (P = 0.8, Fisher's exact test). There was a difference when evaluating the operating times for the pathologic level of acuity (P = 0.002, Kruskal-Wallis test). CONCLUSIONS: Resident level does not affect the operating time in performing laparoscopic cholecystectomy. The pathologic acuity of the gallbladders was distributed similarly for all three groups. There was a difference in mean operating time based on pathologic acuity. Laparoscopic cholecystectomy can be performed in a safe and efficient manner at a teaching institution.

Analysis of expressed sequence tags (ESTs) from the scaly green flagellate Scherffelia dubia Pascher emend. Melkonian et Preisig.

Partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of gene discovery, generation of molecular markers and characterization of transcription patterns. We have constructed an EST-database of the scaly green flagellate Scherffelia dubia (Chlorophyta) containing 361 sequences. cDNAs were obtained from interphase cells and from cells regenerating flagella. Analysis of the ESTs identified 138 EST-groups with significant similarity to known sequences. 134 EST-groups showed no significant similarity to any sequences in the databases. Most of the ESTs with similarity to known proteins are associated with typical interphase cell functions of a photosynthetic plant cell: assimilation of nutrients and biosynthesis of proteins. Others are related to the activation of the secretory pathway or the biogenesis of scales (e.g. kdo-synthase). Comparison of S. dubia ESTs with the genome of Arabidopsis thaliana and the EST database of Chlamydomonas reinhardtii revealed that S. dubia ESTs with similarity to known proteins were more similar to sequences in C. reinhardtii than to those of A. thaliana. Additionally, ESTs for guanylyl cyclase and cGMP phosphodiesterase are present in the two flagellates, but so far these gene products have not been found in embryophytes.

A virtual reality surgical trainer for navigation in laparoscopic surgery.

A virtual reality trainer was designed to familiarize students and surgeons with surgical navigation using an angled laparoscopic lens and camera system. Previous laparoscopic trainers have been devoted to task or procedure training. Our system is exclusively devoted to laparoscope manipulation and navigation. Laparoscopic experts scored better than novices in this system suggesting construct validity. The trainer received favorable subjective ratings. This simulator may provide for improved navigation in the operating room and become a useful tool for residents and practicing surgeons.

A prototype haptic suturing simulator.

A new haptic simulation designed to teach basic suturing for simple wound closure is described. Needle holders are attached to the haptic device as the graphics of the needle holders, needle, sutures and virtual skin are displayed and updated in real time. The simulator incorporates several interesting components such as real-time modeling of deformable skin, tissue and suture material and real-time recording of state of activity during the task using a finite state model.

Are surgery training programs ready for virtual reality? A survey of program directors in general surgery.

BACKGROUND: The use of advanced technology, such as virtual environments and computer-based simulators (VR/CBS), in training has been well established by both industry and the military. In contrast the medical profession, including surgery, has been slow to incorporate such technology in its training. In an attempt to identify factors limiting the regular incorporation of this technology into surgical training programs, a survey was developed and distributed to all general surgery program directors in the United States. STUDY DESIGN: A 22-question survey was sent to 254 general surgery program directors. The survey was designed to reflect attitudes of the program directors regarding the use of computer-based simulation in surgical training. Questions were scaled from 1 to 5 with 1 = strongly disagree and 5 = strongly agree. RESULTS: A total of 139 responses (55%) were returned. The majority of respondents (58%) had seen VR/CBS, but only 19% had "hands-on" experience with these systems. Respondents strongly agreed that there is a need for learning opportunities outside of the operating room and a role for VR/CBS in surgical training. Respondents believed both staff and residents would support this type of training. Concerns included VR/CBS' lack of validation and potential requirements for frequent system upgrades. CONCLUSIONS: Virtual environments and computer-based simulators, although well established training tools in other fields, have not been widely incorporated into surgical education. Our results suggest that program directors believe this type of technology would be beneficial in surgical education, but they lack adequate information regarding VR/CBS. Developers of this technology may need to focus on educating potential users and addressing their concerns.

Molecular phylogeny and taxonomic revision of Chlamydomonas (Chlorophyta). I. Emendation of Chlamydomonas Ehrenberg and Chloromonas Gobi, and description of Oogamochlamys gen. nov. and Lobochlamys gen. nov.

The genus Chlamydomonas (including Chloromonas) is one of the largest green algal genera comprising more than 600 species. To initiate a comprehensive analysis of the phylogeny and systematics of the genus, we determined nuclear-encoded SSU rRNA sequences from 32 strains of Chlamydomonas, Chloromonas and Chlorogonium with emphasis on oogamous taxa and related strains, and incorporated these into global molecular phylogenetic analyses of 132 strains of Chlorophyceae. In addition, we studied the morphology and reproduction of oogamous and related strains by light microscopy. We recognize and designate 18 monophyletic lineages (clades) within the Chlorophyceae, 11 of which are confined to the CW (basal bodies displaced clockwise) subgroup. The majority of clades recognized within the Chlorophyceae do not correspond to any of the traditional classification systems, which are still largely based on the organization level. Strains assigned to Chlamydomonas and Chloromonas were found in seven different clades confirming the polyphyly of the two genera as presently conceived. To initiate the taxonomic revision of Chlamydomonas, C. reinhardtii is proposed as the conserved type of the genus. In consequence, species in clades other than the clade containing C. reinhardtii must be transferred to other genera, a process initiated in this contribution. The oogamous strains studied represent a monophyletic lineage, which is described as Oogamochlamys gen. nov. comprising three species (O. gigantea, O. zimbabwiensis and O. ettlii spec. nov.). The sister clade to Oogamochlamys consists of isogamous strains characterized by chloroplasts with incisions and is described as Lobochlamys gen. nov. with two species (L. culleus and L. segnis). Another clade is characterized by asteroid or perforated, parietal chloroplasts and contains the type species of Chloromonas (C. reticulata). Thus, the polyphyletic Chloromonas (traditionally defined as "Chlamydomonas without pyrenoids") can be legitimized as a monophyletic genus by restriction to this clade and is here emended on the basis of chloroplast characters (the clade contains strains with or without pyrenoids thus rejecting the character "absence of pyrenoids").

Flagellar membrane proteins of Tetraselmis striata butcher (Chlorophyta).

Highly purified flagella of the green alga Tetraselmis striata (Chlorophyta) were extracted by Triton X-114 phase partitioning. SDS-PAGE analysis revealed that most proteins were present in the aqueous phase, only two prominent flagellar membrane proteins (fmp) of apparent molecular weight 145 and 57 kDa (fmp145 and fmp57) were enriched in the detergent phase. Fmp145 was purified by gel permeation chromatography. Glycosidase treatment in combination with lectin blot analysis showed that fmp145 is a glycoprotein containing 3-5 N-glycans of the high mannose and/or hybrid type. A polyclonal antibody (anti-fmp136) was raised against the deglycosylated form of fmp145 and used to localize fmp145 by immunofluorescence and immunoelectron microscopy. Immunogold labeling showed fmp145 to be present between the scale layers and the flagellar membrane. During flagellar regeneration fmp145 is incorporated evenly and rapidly into the newly developing flagella. Anti-fmp136 specifically cross-reacted with flagella of only a subgroup of Tetraselmis strains characterized by a specific flagellar hair type (type II according to Marin et al. 1993) and thus could be a useful immunomarker for the identification of Tetraselmis strains by fluorescence microscopy.

The Golgi apparatus of the scaly green flagellate Scherffelia dubia: uncoupling of glycoprotein and polysaccharide synthesis during flagellar regeneration.

The flagella of the green alga Scherffelia dubia are covered by scales which consist of acidic polysaccharides and glycoproteins. Experimental deflagellation results in the regeneration of flagella complete with scales. During flagellar regeneration, scales are newly synthesized in the Golgi apparatus, exocytosed and deposited on the growing flagella. Flagellar regeneration is dependent upon protein synthesis and N-glycosylation, as it is blocked by cycloheximide and partially inhibited by tunicamycin. Metabolic labeling with [35S]methionine/cysteine demonstrated that scale-associated proteins were not newly synthesized during flagellar regeneration, suggesting that the proteins deposited on regenerating flagella were drawn from a pool. Quantitative immunoelectron microscopy using a monospecific antibody directed against a scale-associated protein of 126 kDa (SAP126) revealed that the pool of SAP126 was primarily located at the plasma membrane, with minor labeling of the scale reticulum and trans-Golgi cisternae, both before deflagellation and during flagellar regeneration. Since SAP126 was sequestered during flagellar regeneration into secretory vesicles together with newly synthesized scales, it is concluded that the persistent presence of SAP126 in the trans-Golgi cisternae during scale biogenesis requires retrograde transport of the protein from the plasma membrane to the Golgi apparatus.

Developmental regulation of the maize Zm-p60.1 gene encoding a beta-glucosidase located to plastids.

A beta-glucosidase that cleaves the biologically inactive hormone conjugates cytokinin-O- and kinetin-N3-glucosides is encoded by the maize Zm-p60.1 gene. The expression of the Zm-p60.1 gene was analyzed by Northern blot analysis and in-situ hybridization. It was found that the expression levels of the Zm-p60.1-specific mRNA changed after pollination of carpellate inflorescences. The Zm-p60.1 cDNA was expressed in E. coli and antibodies were raised against this protein. An antibody was used to determine the tissue-specific localization of this protein. By in situ immunolocalization experiments, this protein was found to be located in cell layers below the epidermis and around the vascular bundles of the coleoptile. In the primary leaf, the Zm-p60.1 protein was detected in cells of the outermost cell layer and around the vascular tissue. In floral tissue, Zm-p60.1 was present in the glumes, the carpels and in the outer cell layer of the style. In coleoptiles, as determined by immuno-electronmicroscopy, the Zmp60.1 protein was located exclusively in the plastids.

V-ATPase is a major component of the Golgi complex in the scaly green flagellate Scherffelia dubia.

Highly purified membranes isolated from the Golgi complex of the scaly green flagellate Scherffelia dubia (Chlorophyta) were subjected to Triton X-114 two-phase partitioning. Proteins in the detergent phase were analyzed by 2D gel electrophoresis and a major protein of 66 kD (p66) was N-terminally sequenced. The complete cDNA sequence of p66 was obtained by 3' RACE-PCR and screening of a cDNA library of S. dubia with a PCR probe derived from the 3' RACE. Sequence analysis of the cDNA clone identified p66 as subunit A of V-ATPase. Other major proteins in the isolated Golgi complex were immunoreactive to heterologous antibodies raised against subunit B or the holoenzyme of V-ATPase. A polyclonal (anti-p66) antibody raised against a recombinant, bacterially expressed p66 fusion protein recognized p66 in the isolated Golgi complex in western blots and localized the antigen by immunogold electron microscopy mostly to the scale reticulum but also to the Golgi stack within the Golgi complex. Concanamycin A-sensitive (but bafilomycin A1-insensitive) ATPase activity was present in the isolated Golgi complex, and monensin at 0.5-1 microM reversibly inhibited flagellar regeneration and resulted in swelling of Golgi cisternae. It is concluded that a functional V-ATPase is a major protein of the Golgi complex in S. dubia and is presumably associated with sorting processes at the endocytotic/exocytotic boundary of the Golgi complex.

Mesostigmatophyceae, a new class of streptophyte green algae revealed by SSU rRNA sequence comparisons.

Complete nuclear-encoded SSU rRNA sequences have been obtained from three taxa of streptophyte green algae (Klebsormidium nitens, Nitella capillaris, Chaetosphaeridium globosum) and two strains of the scaly green flagellate Mesostigma viride. Phylogenetic analyses of 70 taxa of Viridiplantae (Chlorophyta and Streptophyta) and 57 taxa of streptophyte green algae and embryophyte plants using distance, parsimony and likelihood methods revealed a novel monophyletic lineage among the Streptophyta comprising the genera Mesostigma and Chaetosphaeridium. This lineage is described here as the Mesostigmatophyceae classis nova. Our analyses demonstrate that (1) scaly green flagellates (prasinophytes) are polyphyletic, (2) a scaly green flagellate is a member of the Streptophyta and forms a clade with the oogamous, filamentous Chaetosphaeridium to the exclusion of all other known streptophyte green algae, (3) a previously published SSU rRNA sequence of Chaetosphaeridium (AF113506) is chimeric and contains part of a fungal SSU rRNA, and (4) the phylogenetic relationships between the Mesostigmatophyceae and other streptophyte green algae remain unresolved by SSU rRNA sequence comparisons.

SF-assemblin, striated fibers, and segmented coiled coil proteins.

The flagellar basal apparatus of many flagellate green algae contains noncontractile striated microtubule-associated fibers (SMAFs). The SMAFs consist of 2-nm protofilaments and are predominantly built from striated fiber (SF)-assemblin, an acidic 33-kDa protein. In this review we summarize the present knowledge concerning the biochemical properties of SF-assemblin and the molecular architecture of the SMAFs, provide evidence for homologous proteins and similar filament systems in other eukaryotes, and, finally, discuss possible biological functions of SF-assemblin.

A novel 95-kD protein is located in a linker between cytoplasmic microtubules and basal bodies in a green flagellate and forms striated filaments in vitro.

The flagellar basal apparatus comprises the basal bodies and the attached fibrous structures, which together form the organizing center for the cytoskeleton in many flagellated cells. Basal apparatus were isolated from the naked green flagellate Spermatozopsis similis and shown to be composed of several dozens of different polypeptides including a protein band of 95 kD. Screening of a cDNA library of S. similis with a polyclonal antibody raised against the 95-kD band resulted in a full-length clone coding for a novel protein of 834 amino acids (90.3 kD). Sequence analysis identified nonhelical NH2- and COOH-terminal domains flanking a central domain of approximately 650 residues, which was predicted to form a series of coiled-coils interrupted by short spacer segments. Immunogold labeling using a polyclonal antibody raised against the bacterially expressed 95-kD protein exclusively decorated the striated, wedge-shaped fibers, termed sinister fibers (sf-fibers), attached to the basal bodies of S. similis. Striated fibers with a periodicity of 98 nm were assembled in vitro from the purified protein expressed from the cloned cDNA indicating that the 95-kD protein could be a major component of the sf-fibers. This structure interconnects specific triplets of the basal bodies with the microtubular bundles that emerge from the basal apparatus. The sf-fibers and similar structures, e.g., basal feet or satellites, described in various eukaryotes including vertebrates, may be representative for cytoskeletal elements involved in positioning of basal bodies/centrioles with respect to cytoskeletal microtubules and vice versa.