Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

Internal Transcribed Spacer 2 (nu ITS2 rRNA) Sequence-Structure Phylogenetics: Towards an Automated Reconstruction of the Green Algal Tree of Life

L). Some have advocated the use of the nuclear-encoded, internal transcribed spacer two (ITS2) as an alternative to the traditional chloroplast markers. However, the ITS2 is broadly perceived to be insufficiently conserved or to be confounded by introgression or biparental inheritance patterns, precluding its broad use in phylogenetic reconstruction or as a DNA barcode. A growing body of evidence has shown that simultaneous analysis of nucleotide data with secondary structure information can overcome at least some of the limitations of ITS2. The goal of this investigation was to assess the feasibility of an automated, sequence-structure approach for analysis of IT2 data from a large sampling of phylum Chlorophyta.Sequences and secondary structures from 591 chlorophycean, 741 trebouxiophycean and 938 ulvophycean algae, all obtained from the ITS2 Database, were aligned using a sequence structure-specific scoring matrix. Phylogenetic relationships were reconstructed by Profile Neighbor-Joining coupled with a sequence structure-specific, general time reversible substitution model. Results from analyses of the ITS2 data were robust at multiple nodes and showed considerable congruence with results from published phylogenetic analyses.Our observations on the power of automated, sequence-structure analyses of ITS2 to reconstruct phylum-level phylogenies of the green algae validate this approach to assessing diversity for large sets of chlorophytan taxa. Moreover, our results indicate that objections to the use of ITS2 for DNA barcoding should be weighed against the utility of an automated, data analysis approach with demonstrated power to reconstruct evolutionary patterns for highly divergent lineages

Paleontology of leaf beetles

`The rate of evolution in any large group is not uniform; there are periods of relatise stability, and periods of comparatively rapid change.&apos; Cockerell and LeVeque, 1931 To Yenli Ych, my beloved wife, a most wonderful person! The fossil record of the Chrysomelidae can be tentatively traced back to the late Paleozoic to early Mesozoic Triassic. Mesozoic records at least 9 subfamilies, 19 genera, and 35 species, are represented by the Sagrinae, the exclusively Mesozoic Proto scelinae, Clytrinae, Cryptocephalinae, Eumolpinae, Chrysomelinae. Galerucinac, Alticinae, and Cassidinae. Cenozoic records at least 12 subfamilies- 63 % of the extant- 12! genera, and 325 species, include the same extant subfamilies as well as the Donaciinae, Zeugophorinae, Criocerinae, and Hispinae and can be frequently identified to genus, especially if preserved in amber. Quaternary records are often identified to extant species. tn total, at least t3! genera about 4 % of total extant, and 357 species &lt; 1 % have been reported. At least, 24 genera &lt;1 % of the extant seem to be extinct. Although reliable biological information associated with the fossil chrysomelids is very scarce, it seems that most of the modern host-plant associations were established, at least, in the late Mesozoic to early Cenozoic. As a whole, stasis seems to be the general rule of the chrysomelid fossil record. Together with other faunal elements, chrysomelids, especially donaciines, have been used as biogeographic and paleoclimatological indicators in the Holocene. I

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Novelty

Novelty, defined as the quality of being new, has always been associated with a vast range of phenomena which had never existed before. The concept is of particular relevance espe- cially in the fields of science, technology, and art, because they mutually deal with discovery, innovation, and invention. As it is apparent, the three disciplines mutually share the impor- tance of creative processes, which lie at their very core. For this reason, the main investiga- tions on novelty, both theoretical and empiri- cal, from the twentieth century onward have mainly been carried out by philosophical and psychological studies related to creativity. Novelty indeed represents one of the funda- mental criteria of creativity. Accordingly, this entry (1) begins with a general, phenomeno- logical description of novelty, (2) points out the current relevance of novelty, (3) focuses on its history by providing a theoretical framework for its understanding, (4) explores different empirical researches and cognitive models of novelty elaborated hitherto, and (5) illustrates the fundamental relation between novelty and the possible