Early and empirical high-dose cryoprecipitate for hemorrhage after traumatic injury: The CRYOSTAT-2 randomized clinical trial

Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage. To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol. CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion. Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury. The primary outcome was all-cause mortality at 28 days in the intention-to-treat population. Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%). Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality. ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314

Enigmatic treehopper genera (Hemiptera: Membracidae): Deiroderes Ramos, Holdgatiella Evans, and Togotolania, new genus

Volume: 104Start Page: 868End Page: 88

Two ancient bacterial endosymbionts have coevolved with the planthoppers (Insecta: Hemiptera: Fulgoroidea)

<p>Abstract</p> <p>Background</p> <p>Members of the hemipteran suborder Auchenorrhyncha (commonly known as planthoppers, tree- and leafhoppers, spittlebugs, and cicadas) are unusual among insects known to harbor endosymbiotic bacteria in that they are associated with diverse assemblages of bacterial endosymbionts. Early light microscopic surveys of species representing the two major lineages of Auchenorrhyncha (the planthopper superfamily Fulgoroidea; and Cicadomorpha, comprising Membracoidea [tree- and leafhoppers], Cercopoidea [spittlebugs], and Cicadoidea [cicadas]), found that most examined species harbored at least two morphologically distinct bacterial endosymbionts, and some harbored as many as six. Recent investigations using molecular techniques have identified multiple obligate bacterial endosymbionts in Cicadomorpha; however, much less is known about endosymbionts of Fulgoroidea. In this study, we present the initial findings of an ongoing PCR-based survey (sequencing 16S rDNA) of planthopper-associated bacteria to document endosymbionts with a long-term history of codiversification with their fulgoroid hosts.</p> <p>Results</p> <p>Results of PCR surveys and phylogenetic analyses of 16S rDNA recovered a monophyletic clade of Betaproteobacteria associated with planthoppers; this clade included <it>Vidania fulgoroideae</it>, a recently described bacterium identified in exemplars of the planthopper family Cixiidae. We surveyed 77 planthopper species representing 18 fulgoroid families, and detected <it>Vidania</it> in 40 species (representing 13 families). Further, we detected the <it>Sulcia</it> endosymbiont (identified as an obligate endosymbiont of Auchenorrhyncha in previous studies) in 30 of the 40 species harboring <it>Vidania</it>. Concordance of the <it>Vidania</it> phylogeny with the phylogeny of the planthopper hosts (reconstructed based on sequence data from five genes generated from the same insect specimens from which the bacterial sequences were obtained) was supported by statistical tests of codiversification. Codiversification tests also supported concordance of the <it>Sulcia</it> phylogeny with the phylogeny of the planthopper hosts, as well as concordance of planthopper-associated <it>Vidania</it> and <it>Sulcia</it> phylogenies.</p> <p>Conclusions</p> <p>Our results indicate that the Betaproteobacterium <it>Vidania</it> is an ancient endosymbiont that infected the common ancestor of Fulgoroidea at least 130 million years ago. Comparison of our findings with the early light-microscopic surveys conducted by Müller suggests that <it>Vidania</it> is Müller’s <it>x</it>-symbiont, which he hypothesized to have codiversified with most lineages of planthoppers and with the <it>Sulcia</it> endosymbiont.</p

A remarkable new species of spittlebug and a second living New World genus in the Clastopteridae (Hemiptera: Cercopoidea)

Paladini, Andressa, Thompson, Vinton, Bell, Adam J., Cryan, Jason R. (2020): A remarkable new species of spittlebug and a second living New World genus in the Clastopteridae (Hemiptera: Cercopoidea). Zootaxa 4852 (3): 361-371, DOI: 10.11646/zootaxa.4852.3.

Table S1 - Voucher Data

Voucher information for specimens included in the phylogenetic analyses

Characters scores

Matrices used in the stochastic mapping of pronotal trai

Data from: A phylogeny of the treehopper subfamily Heteronotinae reveals convergent pronotal traits (Hemiptera: Auchenorrhyncha: Membracidae)

Even within an insect family famous for its morphological diversity, the treehopper subfamily Heteronotinae is a microcosm of pronotal variation, displaying remarkably dissimilar thoracic ornamentations among its ten included genera. Presented here is a reconstruction of heteronotine relationships based on DNA nucleotide sequence data from five nuclear and two mitochondrial genes from a comprehensive sample of ingroup taxa (including exemplars of all genera except for the monotypic Dysyncritus Fowler, 1895). Concordant phylogenetic estimates support the monophyly of Heteronotinae sensu stricto (i.e. excluding Darnoides Fairmaire, 1846), as well as the monophyly of the included genera Heteronotus Laporte, 1832, Nassunia Stål, 1862, Omolon Walker, 1862, Rhexia Stål, 1867, and Smiliorachis Fairmaire, 1846. Conversely, Anchistrotus Buckton, 1902, Allodrilus Evangelista, 2014 and Iria Stål, 1867 were not recovered as monophyletic, although topology comparison tests failed to reject the nonmonophyly of the latter two genera, nor Heteronotinae, as currently circumscribed. These results are interpreted in the context of available morphological evidence, which generally supports these findings. Also addressed here is the evolution of selected pronotal features representing major aspects of heteronotine morphology. Bayesian stochastic mapping of pronotal traits estimated multiple character state transitions, suggesting repeated acquisition of pronotal features, most of which have evolved independently within the diverse genus Heteronotus. These convergences may provide insight into the role of the pronotum in heteronotine groups that appear to serve different adaptive strategies, such as mimicry, crypsis and defence against predators. Furthermore, our results show a substantial diversity in need of formal description, including possible new genera, and several unique sexually dimorphic syndromes that may constitute a species complex within Heteronotus delineatus Walker, 1858. Nomenclatural changes are proposed for Nassunia nigromacula (Funkhouser, 1940) new combination and Smiliorachis inornata Stål, 1862 combination reinstated, which were found to be misplaced at the generic and subfamily levels according to our analyses

Random Amplified Polymorphic DNA and Amplified Fragment Length Polymorphism Analyses of Pasteurella multocida Isolates from Fatal Fowl Cholera Infections

Fowl cholera, a disease caused by Pasteurella multocida, continues to be a major problem for the poultry industry. The sources of pathogenic organisms responsible for most sporadic epidemics remain unconfirmed, although attenuated vaccines that retain a low level of virulence have occasionally been implicated in outbreaks of the disease. One of the vaccines most commonly used to prevent fowl cholera is the M-9 strain. In the present study, 61 clinical isolates from turkeys that died of fowl cholera from 1997 to 1999 on 36 Utah farms were analyzed and compared to the M-9 vaccine strain. Genetic analyses of the isolates were done by random amplified polymorphic DNA (RAPD) analysis and amplified fragment length polymorphism (AFLP) fingerprinting. The results of these genetic analyses were correlated with the vaccination status of the flock, isolate serotype, and geographic location. Although both genetic techniques effectively identified similar subtle genomic differences, RAPD analysis provided only 77% of the detail provided by AFLP analysis. While a relationship between genetic profile and serotype was evident, no significant relationship indicating geographic influence was found (P = 0.351). Interestingly, organisms isolated from vaccinated flocks were significantly closer genetically to the M-9 vaccine strain than isolates from unvaccinated birds were (P = 0.020). Statistical analyses revealed that this relationship could not have been determined by serotyping alone (P = 0.320), demonstrating the value of AFLP and RAPD analyses in the characterization of disease-causing strains

Involvement of Sigma-1 Receptors in the Antidepressant-like Effects of Dextromethorphan

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ(1)) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ(1) receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ(1) receptor antagonists (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ(1) receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ(1) receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a K(i) concentration of dextromethorphan reduces both the K(d) and the B(max) of [(3)H](+)-pentazocine binding to σ(1) receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ(1) receptors