An Insight into the Role of Postmortem Immunohistochemistry in the Comprehension of the Inflammatory Pathophysiology of COVID-19 Disease and Vaccine-Related Thrombotic Adverse Events: A Narrative Review

On 11 March 2020, the World Health Organization (WHO) declared a pandemic due to the spread of COVID-19 from Wuhan, China, causing high mortality rates all over the world. The related disease, which mainly affects the lungs, is responsible for the onset of Diffuse Alveolar Damage (DAD) and a hypercoagulability state, frequently leading to Severe Acute Respiratory Syndrome (SARS) and multiorgan failure, particularly in old and severe-critically ill patients. In order to find effective therapeutic strategies, many efforts have been made aiming to shed light on the pathophysiology of COVID-19 disease. Moreover, following the late advent of vaccination campaigns, the need for the comprehension of the pathophysiology of the fatal, although rare, thrombotic adverse events has become mandatory as well. The achievement of such purposes needs a multidisciplinary approach, depending on a correct interpretation of clinical, biochemical, biomolecular, and forensic findings. In this scenario, autopsies have helped in defining, on both gross and histologic examinations, the main changes to which the affected organs undergo and the role in assessing whether a patient is dead “from” or “with” COVID-19, not to mention whether the existence of a causal link exists between vaccination and thrombotic adverse events. In the present work, we explored the role of postmortem immunohistochemistry, and the increasingly used ancillary technique, in helping to understand the mechanism underlying the pathophysiology of both COVID-19 disease and COVID-19 vaccine-related adverse and rare effects.     

Molding of syndiotactic polystyrene under its melting temperature

Syndiotactic polystyrene (SPS), a thermoplastic polymer that exhibits a high T_m in some crystalline forms, can be conveniently processed by a cold‐compaction technique. Processing temperatures in the range of 150–210°C, well below the T_m, gives rise to physicomechanical properties comparable and even better than those obtained by thermal compression or injection molding. The optimum treatment temperature seems to fall around 175°C. X‐ray diffraction analysis, thermal analysis, and density measurements suggest that such behavior is connected to phase transitions of SPS and favored by the presence of styrene included in the crystalline fraction. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 377–383, 2001     

Mechanistic study of the redox process of an in situ oxidatively polymerised poly(3,4-ethylene-dioxythiophene) film

The redox process mechanism responsible for the colour change in poly(3,4-ethylene-dioxythiophene) (PEDOT) was investigated in order to understand the nature and the role of the chemical species involved. PEDOT layers were obtained by chemical polymerisation with iron (III) p-toluenesulphonate. The films were then cycled several times in LiClO₄/propylene carbonate (PC) electrolyte. The chemical composition of ‘as-prepared’ and cycled films (in the reduced and oxidised state) was studied by means of EDX and XPS ex situ analysis. The results point out the fundamental role the electrolyte anion plays in the process and provide quantitative information about the extent of anion exchange.     

Limits of optical transmission measurements with application to particle sizing techniques

Considerable confusion exists regarding the applicability limits of the Bouguer-Lambert-Beer law of optical transmission. We review the derivation of the law and discuss its application to the optical thickness of the light-scattering medium. We demonstrate the range of applicability by presenting a method for determining particle size by measuring optical transmission at two wavelengths.     

Design and technical status of the EU contribution to ITER

Europe is involved in the procurement of most of the high-technology items for the ITER device (e.g. parts of the superconducting Toroidal (TF) and Poloidal Field (PF) coils, the vacuum vessel (VV), the in-vessel components, the remote handling, the additional heating systems, the tritium plant and cryoplant and finally parts of the diagnostics). In many cases the technologies required to manufacture these components are well established, in others there is still ongoing design and R&D work to select and optimise the final design solutions and to consolidate the underlying technologies as, for example, in the areas of heating and current drive, plasma diagnostics, shield blanket and first wall, remote handling, etc. A design review has recently been conducted by the ITER Organisation, with the support of the Domestic Agencies (DAs) established by the countries participating to ITER, to address the remaining outstanding technical issues and understand the associated implications for design, machine performance, schedule and cost.This paper provides an update of the design and technical status of EU contributions to ITER.     

Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line

This study evaluates the effects of five different peptides, the Epitalon^® tetrapeptide, the Vilon^® dipeptide, the Thymogen^® dipeptide, the Thymalin^® peptide complex, and the Chonluten^® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides^®), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific. We tested the capacity of the five peptides to influence cell cultures in vitro by incubating THP-1 cells with peptides at certain concentrations known for being effective on recipient cells in culture. We found that all five peptides can modulate key proliferative patterns, increasing tyrosine phosphorylation of mitogen-activated cytoplasmic kinases. In addition, the Chonluten tripeptide, derived from bronchial epithelial cells, inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action. Therefore, all peptides inhibited the expression of TNF and pro-inflammatory IL-6 cytokine stimulated by LPS on terminally differentiated THP-1 cells. Lastly, by incubating the THP1 cells, treated with the peptides, on a layer of activated endothelial cells (HUVECs activated by LPS), we observed a reduction in cell adhesion, a typical pro-inflammatory mechanism. Overall, the results suggest that the Khavinson Peptides^® cooperate as natural inducers of TNF tolerance in monocyte, and act on macrophages as anti-inflammatory molecules during inflammatory and microbial-mediated activity.     

Oxidative Stress,Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan

Furan is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vivo have been performed to investigate furan genotoxicity, the results are inconsistent, and its carcinogenic mode of action remains to be clarified. Here, we address the mutagenic and clastogenic activity of furan and its prime reactive metabolite cis-2 butene-1,4-dial (BDA) in mammalian cells in culture and in mouse animal models in a search for DNA lesions responsible of these effects. To this aim, Fanconi anemia-derived human cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) and Ogg1^−/− mice defective in the removal of 8-hydroxyguanine from DNA, were used. We show that both furan and BDA present a weak (if any) mutagenic activity but are clear inducers of clastogenic damage. ICLs are strongly indicated as key lesions for chromosomal damage whereas oxidized base lesions are unlikely to play a critical role.     

Models for the schedule optimization problem at a public transit terminal

This work deals with the proposal of some models for the schedule optimization problem for public transit networks. In particular, we consider the case of a transit terminal where passengers are supposed to split among different lines of a service, or even change mode of transportation in case of intermodal systems. Starting from a given schedule for the transit lines arriving at the terminal, the aim is to decide the optimal schedule for the output lines, in such a way to balance the operative costs of the service and the passenger waiting time at the transit terminal. We propose two different models for this problem, which present strong similarities with some well known combinatorial optimization models. Computational results are also presented, showing the suitability of the models to solve real case studies.