Origin of Nepheline-normative High-K Ankaramites and the Evolution of Eastern Srednogorie Arc in SE Europe

Eastern Srednogorie is part of the Apuseni-Banat-Timok-Srednogorie magmatic belt in SE Europe, the main arc related to the Late Cretaceous subduction and closure of the Tethys Ocean between Africa and Europe. Extrusive and shallow intrusive magmatism in the Eastern Srednogorie is abundant and extremely diverse in composition, covering a wide range from ultramafic volcanic rocks to granites; this provides a unique opportunity to study processes of primitive melt formation and magma evolution in an arc environment. In contrast to other parts of the belt, relatively mafic lavas predominate here. Three magmatic regions are distinguished within Eastern Srednogorie from south to north: Strandzha, Yambol-Burgas and East Balkan. Systematic differences exist between these regions, notably the increased alkalinity of samples from the Yambol-Burgas region in the central part. All rocks display a clear subduction-like signature in their trace-element patterns, particularly the enrichment in large ion lithophile elements and light rare earth elements relative to high field strength elements. A distinct primitive nepheline-normative ankaramite magma type is recognized among the mafic volcanic rocks from the Yambol-Burgas region and melt inclusions entrapped in olivine and clinopyroxene from a cumulitic rock. Lower crustal clinopyroxene and amphibole cumulates carried to the surface as xenoliths in a mafic dike represent a possible source for the ankaramite. Modeling of the melting process suggests that low degrees of batch melting of a clinopyroxene-rich, amphibole-bearing source similar to the cumulate xenoliths at 1 GPa, temperatures of 1240-1300°C, oxidized conditions and a water content of 0·2 wt % reproduce accurately most of the observed major- and trace-element characteristics of the studied ankaramites. The elevated Rb, K2O, Th, Ba content and higher Pb isotope ratios of the predicted liquids compared with the ankaramites are explained by mixing of the ankaramite magma with lherzolite partial melts derived from the subduction-modified mantle wedge. Underplating of such mantle-derived magmas at the crust-mantle boundary in an extensional environment as a response to slab roll-back provides also the necessary heat to melt lower crustal cumulates. Fractional crystallization of mainly clinopyroxene plus olivine and Fe-Ti oxides in a deep (equivalent to 8 kbar pressure) magma chamber produced most of the observed range of shoshonitic basalts and basaltic andesites in Eastern Srednogorie. The more evolved intermediate varieties were probably formed by mixing and crystallization at lower temperatures in lower pressure magma chambers. Whole-rock Sr and Pb isotope compositions indicate variable degrees of admixing of basement rocks to generate the intermediate to acid Late Cretaceous magmas, but assimilation was minimal for magmas with less than 53 wt % SiO2. The proposed model for the evolution of the magmatism in Eastern Srednogorie involves initial formation of the calc-alkaline and high-K arc magmatism in the Strandzha and East Balkan regions, followed by roll-back induced intra-arc rifting and the formation of high-K, shoshonitic and ultra-high-K magmatism, including primitive ankaramites in the Yambol-Burgas regio

Autopsy findings in COVID-19-related deaths. A literature review

Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease

The importance of being little: MA-XRF on manuscripts on a Venetian island

The XRF scanning spectrometer developed in the framework of CHNet-INFN (Cultural Heritage Network - National Institute of Nuclear Physics), is specifically customised for cultural heritage applications, designed with a focus on having a lightweight scanner (weighing approximately 10 kg), easy to handle and thus easily transportable in two medium-sized boxes. The research presented here deals with the study of a set of choir books preserved in the Abbey of San Giorgio Maggiore on the homonymous island in Venice. Produced for the Abbey itself from the mid-15th century onwards, the manuscripts have never left the island, making the study of the materials of particular interest as they have undergone little or no modification over time. During their history in the Abbey, however, the volumes have been disassembled and reassembled in various ways, bringing complexity to the current cataloguing work. Thus, analytical investigations of the pigments and painting techniques might help identify the original arrangement of displaced leaves and provide evidence for the attribution of individual illuminations to certain artists. Thanks to its easy transportability, it was possible to take the scanner to the small island by means of the water-based Venetian public transport. Selected results are presented, derived from the high-quality MA-XRF maps obtained

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.

A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new 1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies