Ticagrelor inverse agonist activity at the P2Y12 receptor is non-reversible versus its endogenous agonist adenosine 5´-diphosphate

Background Ticagrelor is labelled as a reversible, direct-acting platelet P2Y12 receptor (P2Y12R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients which in emergency situations requires platelet transfusion although there is ongoing debate on its effectiveness following ticagrelor therapy. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y12R. Methods Studies were performed in human platelets with both P2Y12R-stimulated GTPase activity and platelet aggregation assessed. Cell-based bioluminescence resonance energy transfer (BRET) assays were also undertaken to assess G protein subunit activation downstream of P2Y12R activation. Results Initial studies revealed a range of P2Y12R ligands including ticagrelor displayed inverse agonist activity at the P2Y12R. Of these only ticagrelor was resistant to wash-out. In both human platelets and cell-based assays, washing failed to reverse ticagrelor-dependent inhibition of ADP-stimulated P2Y12R function in contrast to other P2Y12R antagonists. The P2Y12R agonist 2MeSADP, which was also resistant to wash-out, was able to effectively compete with ticagrelor. In silico docking revealed that ticagrelor and 2MeSADP penetrated more deeply into the orthosteric binding pocket of the P2Y12R than other P2Y12R ligands. Conclusion Ticagrelor binding to the P2Y12R is prolonged and more akin to that of an irreversible antagonist especially versus the endogenous P2Y12R agonist ADP. This study highlights the potential clinical need for novel ticagrelor reversal strategies in patients with spontaneous major bleeding and bleeding associated with urgent invasive procedures

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multicentre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients’ (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16–22) and failed intubation in 1 in 312 (95%CI 1 in 169–667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

First Report of \u3ci\u3eCurvularia inaequalis\u3c/i\u3e and \u3ci\u3eBipolaris spicifera\u3c/i\u3e Causing Leaf Blight of Buffalograss in Nebraska

During the summer of 2011, foliar blight was observed on buffalograss (Buchloë dactyloides (Nutt.) Engelm.) lawns in Lincoln and Waverly, Nebraska. Disease symptoms were common when buffalograss was growing above 30°C and in drought conditions. Disease symptoms began as dark brown oblong leaf spots, followed by leaf tip dieback and eventual blighting of entire tillers. Leaf infections would progress into patches of thinning turf. Diseased leaf pieces were rinsed in distilled water and placed on 1.5% water agar. Two mitosporic fungal species having conidial morphology of Curvularia and Bipolaris were isolated. Colonies of Curvularia isolates grown on ¼× PDA at 25°C appeared velvety and dark greenish to grayish black after 1 week while Bipolaris cultures were brownish gray with olive green margins

DNA fingerprinting and anastomosis grouping reveal similar genetic diversity in \u3ci\u3eRhizoctonia species\u3c/i\u3e infecting turfgrasses in the transition zone of USA

Rhizoctonia blight is a common and serious disease of many turfgrass species. The most widespread causal agent, Thanatephorus cucumeris (anamorph: R. solani), consists of several genetically different subpopulations. In addition, Waitea circinata varieties zeae, oryzae and circinata (anamorph: Rhizoctonia spp.) also can cause the disease. Accurate identification of the causal pathogen is important for effective management of the disease. It is challenging to distinguish the specific causal pathogen based on disease symptoms or macroscopic and microscopic morphology. Traditional methods such as anastomosis reactions with tester isolates are time consuming and sometimes difficult to interpret. In the present study universally primed PCR (UP-PCR) fingerprinting was used to assess genetic diversity of Rhizoctonia spp. infecting turfgrasses. Eighty-four Rhizoctonia isolates were sampled from diseased turfgrass leaves from seven distinct geographic areas in Virginia and Maryland. Rhizoctonia isolates were characterized by ribosomal DNA internal transcribed spacer (rDNAITS) region and UP-PCR. The isolates formed seven clusters based on ITS sequences analysis and unweighted pair group method with arithmetic mean (UPGMA) clustering of UP-PCR markers, which corresponded well with anastomosis groups (AGs) of the isolates. Isolates of R. solani AG 1-IB (n=18), AG 2-2IIIB (n=30) and AG 5 (n=1) clustered separately. Waitea circinata var. zeae (n=9) and var. circinata (n=4) grouped separately. A cluster of six isolates of Waitea (UWC) did not fall into any known Waitea variety. The binucleate Rhizoctonia-like fungi (BNR) (n=16) clustered into two groups. Rhizoctonia solani AG 2-2IIIB was the most dominant pathogen in this study, followed by AG 1-IB. There was no relationship between the geographic origin of the isolates and clustering of isolates based on the genetic associations. To our knowledge this is the first time UP-PCR was used to characterize Rhizoctonia, Waitea and Ceratobasidium isolates to their infraspecies level

Porocercospora seminalis gen. et comb. nov., the causal organism of buffalograss false smut

False smut caused by Cercospora seminalis is an important disease of buffalograss (Buchloë dactyloides) affecting seed production. The pathogen prevents normal caryopsis development and causes considerable yield loss and reduced seed germination. The current taxonomic placement of the false-smut causal pathogen in the genus Cercospora is incorrect based on its morphological characteristics and DNA phylogeny. In the present study the phylogenetic position of C. seminalis is clarified based on DNA sequence analysis of three loci namely the internal transcribed spacer (ITS) region, partial nuclear ribosomal large subunit (LSU) and partial sequences of the RNA polymerase II second largest subunit (RPB2). A collection of C. seminalis isolates was made from buffalograss sites near Lincoln, Nebraska. DNA sequence data indicated that Cercospora seminalis is phylogenetically close to but distinct from species of Bipolaris and Curvularia (Pleosporaceae, Pleosporales). Cercospora seminalis morphologically had unique characteristics, namely densely aggregated and repeatedly branched conidiophores arising from a brown stroma, monotretic conidiogenous cells with inconspicuous loci, and scolecosporous conidia with distosepta, and thickened, darkened hila. Porocercospora is introduced as a new genus to accommodate the buffalograss false-smut pathogen

Not Available

Not AvailableRhizoctonia isolates collected from seven diverse maize cropping zones of India were examined for morphological and molecular variability. All the tested isolates caused symptoms of BLSB on maize and were also cross infective on rice and sugarcane hosts, but showed significant variability in hyphal diameter, mean hyphal cell size, weight, size and distribution of scleorotia, culture pigmentation, incubation period, pathogenicity and expression of symptoms. Neighbour joining cluster analysis placed the 62 isolates of R. solani into four major groups, A, B, C and D. Group Awas more diverse and included isolates of diverse agroecological zones. The cluster analysis corresponded well with principle component analysis. Pathogenicity testing of R. solani isolates on maize genotype (CM 501) revealed highly variable virulence pattern of the pathogen population suggesting its high evolutionary potential, and hence adaptability to diverse geographical regions. The study reveals a strong evidence of inherent potential of the R. solani isolates to survive in diverse ecological zones and its probable spread to other maize cultivars across India. Sequence comparisons of the internal transcribed sequence-ribosomal DNA region of 62 isolates did not reveal much diversity among the isolates. Majority of the isolates (n = 61) clustered together with anastomosis group (AG) AG1-IA used as reference strain in the phylogram, distinct from AG1-IB, AG2–2IIIB and Waitea circinata used as reference strains. BLSB isolates representing distinct geographical locations shared identical sequences indicating long-distance dispersal of the pathogen. The study confirms that the genetic flexibility of the pathogen allows for its adaptation to variable ecological niches and long-distance introduction of new genotypes into the region. The study emphasizes that epidemiological studies may complement the molecular studies.Not Availabl

Notes for genera – Ascomycota

Knowledge of the relationships and thus the classification of fungi, has developed rapidly with increasingly widespread use of molecular techniques, over the past 10--15 years, and continues to accelerate. Several genera have been found to be polyphyletic, and their generic concepts have subsequently been emended. New names have thus been introduced for species which are phylogenetically distinct from the type species of particular genera. The ending of the separate naming of morphs of the same species in 2011, has also caused changes in fungal generic names. In order to facilitate access to all important changes, it was desirable to compile these in a single document. The present article provides a list of generic names of Ascomycota (approximately 6500 accepted names published to the end of 2016), including those which are lichen-forming. Notes and summaries of the changes since the last edition of `Ainsworth Bisby's Dictionary of the Fungi' in 2008 are provided. The notes include the number of accepted species, classification, type species (with location of the type material), culture availability, life-styles, distribution, and selected publications that have appeared since 2008. This work is intended to provide the foundation for updating the ascomycete component of the ``Without prejudice list of generic names of Fungi'' published in 2013, which will be developed into a list of protected generic names. This will be subjected to the XIXth International Botanical Congress in Shenzhen in July 2017 agreeing to a modification in the rules relating to protected lists, and scrutiny by procedures determined by the Nomenclature Committee for Fungi (NCF). The previously invalidly published generic names Barriopsis, Collophora (as Collophorina), Cryomyces, Dematiopleospora, Heterospora (as Heterosporicola), Lithophila, Palmomyces (as Palmaria) and Saxomyces are validated, as are two previously invalid family names, Bartaliniaceae and Wiesneriomycetaceae. Four species of Lalaria, which were invalidly published are transferred to Taphrina and validated as new combinations. Catenomycopsis Tibell Constant. is reduced under Chaenothecopsis Vain., while Dichomera Cooke is reduced under Botryosphaeria Ces. De Not. (Art. 59)