Acute Generalized Exanthematous Pustulosis: Pathogenesis,Genetic Background,Clinical Variants and Therapy

Acute generalized exanthematous pustulosis (AGEP) is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base and spontaneous resolution usually within two weeks. Systemic involvement occurs in about 20% of cases. The course is mostly benign, and only in rare cases complications lead to life-threatening situations. Recent studies highlight the importance of genetic variations in interleukin-36 receptor antagonist gene (IL-36RN) in the pathogenesis of this disease. The physiopathology of AGEP remains unclear, but an involvement of innate and acquired immune cells together with resident cells (keratinocytes), which recruit and activate neutrophils via production of cytokines/chemokines such as IL-17, IL-36, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα) and chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, has been postulated. Treatment is based on the removal of the causative drug, supportive care, infection prevention and use of potent topical or systemic steroids.     

Mapping and Characterization of HCMV-Specific Unconventional HLA-E-Restricted CD8 T Cell Populations and Associated NK and T Cell Responses Using HLA/Peptide Tetramers and Spectral Flow Cytometry

HCMV drives complex and multiple cellular immune responses, which causes a persistent immune imprint in hosts. This study aimed to achieve both a quantitative determination of the frequency for various anti-HCMV immune cell subsets, including CD8 T, γδT, NK cells, and a qualitative analysis of their phenotype. To map the various anti-HCMV cellular responses, we used a combination of three HLA_peptide tetramer complexes (HLA-E_VMAPRTLIL, HLA-E_VMAPRSLLL, and HLA-A2_NLVPMVATV) and antibodies for 18 surface markers (CD3, CD4, CD8, CD16, CD19, CD45RA, CD56, CD57, CD158, NKG2A, NKG2C, CCR7, TCRγδ, TCRγδ2, CX3CR1, KLRG1, 2B4, and PD-1) in a 20-color spectral flow cytometry analysis. This immunostaining protocol was applied to PBMCs isolated from HCMV⁻ and HCMV⁺ individuals. Our workflow allows the efficient determination of events featuring HCMV infection such as CD4/CD8 ratio, CD8 inflation and differentiation, HCMV peptide-specific HLA-E_UL40 and HLA-A2_pp65CD8 T cells, and expansion of γδT and NK subsets including δ2⁻γT and memory-like NKG2C⁺CD57⁺ NK cells. Each subset can be further characterized by the expression of 2B4, PD-1, KLRG1, CD45RA, CCR7, CD158, and NKG2A to achieve a fine-tuned mapping of HCMV immune responses. This assay should be useful for the analysis and monitoring of T-and NK cell responses to HCMV infection or vaccines.     

Metabolic Syndrome: Updates on Pathophysiology and Management in 2021

Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome.     

The mixing effect on the free radical MMA solution polymerization

Mathematical models of reactors for the polymerization of methylmethacrylate (MMA) have been developed and analyzed to elucidate reactor dynamics and to determine conditions for improved operation. The effects of mixing and heat transfer in an MMA polymerization reactor system have been explored by the development of an imperfect mixing model. To model imperfect mixing in polymerization, a reactor configuration using two tanks in parallel was used. Bifurcation diagrams developed using numerical analysis of the model have been drawn with two variable parameters, an exchange ratio, σ, and a volume ratio, κ. We use feed and coolant temperatures as bifurcation parameters. If variable parameters are small, the lower solution branch of the steady state solutions is quite different from that of a simple model that assumes perfect macro-mixing as bifurcation parameters change. If σ increases (κ=0.1, σ=1.0), the shape of a steady state solution curve differs significantly from that of a simple model as the feed temperature decreases.     

Composition of bacterial and archaeal communities in freshwater sediments with different contamination levels (Lake Geneva, Switzerland)

The aim of this study was to compare the composition of bacterial and archaeal communities in contaminated sediments (Vidy Bay) with uncontaminated sediments (Ouchy area) of Lake Geneva using 16S rRNA clone libraries. Sediments of both sites were analysed for physicochemical characteristics including porewater composition, organic carbon, and heavy metals. Results show high concentrations of contaminants in sediments from Vidy. Particularly, high contents of fresh organic matter and nutrients led to intense mineralisation, which was dominated by sulphate-reduction and methanogenesis. The bacterial diversity in Vidy sediments was significantly different from the communities in the uncontaminated sediments. Phylogenetic analysis revealed a large proportion of Betaproteobacteria clones in Vidy sediments related to Dechloromonas sp., a group of dechlorinating and contaminant degrading bacteria. Deltaproteobacteria, including clones related to sulphate-reducing bacteria and Fe(III)-reducing bacteria (Geobacter sp.) were also more abundant in the contaminated sediments. The archaeal communities consisted essentially of methanogenic Euryarchaeota, mainly found in the contaminated sediments rich in organic matter. Multiple factor analysis revealed that the microbial community composition and the environmental variables were correlated at the two sites, which suggests that in addition to environmental parameters, pollution may be one of the factors affecting microbial community structure.     

Effect of water‐absorbing nanospheres on antistatic property of isotactic polypropylene fibers

In this article, novel antistatic isotactic polypropylene (iPP) fibers were prepared through adding ternary polymer water‐absorbing nanospheres (TPWANs) into iPP melt in melt spinning process. The TPWANs were synthesized through emulsion copolymerization of styrene (St), butyl acrylate (BA), and sodium allylsulfonate (SAS). The characterization results of Fourier transform infrared spectrometer (FT‐IR) and ¹H nuclear magnetic resonance (¹H NMR) confirmed the ternary components in this copolymer. Transmission electron microscopy (TEM) images indicated the nanospherical shape of TPWANs with the characteristics of 80–90 nm size range of diameter and good dispersion in iPP fibers. The volume resistance of iPP fibers decreased by three orders from 10¹² to 10⁹ Ω cm when the 6 wt % TPWANs was added into iPP fibers, indicating that the blend fibers have good antistatic property. Most importantly, the nanospherical structure of TPWANs imparts both the compatibility and antistatic property into the blend iPP fibers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40568.     

Co-creation of value and the project context: Towards application on the case of Hinkley Point C Nuclear Power Station

The research analyses decisions as evaluative outcomes regarding project value. The UK-French Hinkley Point C Nuclear Power Station provides the case study. Value is traditionally assessed as inputs and outputs. Here, value is conceptualized as a co-created value proposition at the front-end with implications for realization post-completion. Service-dominant logic (SDL) provides the theoretical lens and contributes to a methodological approach for examining projects. Decision-making outcomes provide the evidence from a range of data sources, including reports and commentaries. The methods are interpretative. The findings show that decision-making extends beyond the time-cost-quality/scope dimensions. The long-term issues regarding value realized are often overlooked. Stakeholders and individual actors have mainly focused upon managing political and financial risks, especially time and cost. The research poses challenges to project management analysis, SDL and research design in assessing evidence. Addressing these issues facilitates a knowledge contribution to SDL theorization and the field of project management.     

Sustainability indicators for the assessment of nuclear power

Electricity supplies an increasing share of the world’s total energy demand and that contribution is set to increase. At the same time, there is increasing socio-political will to mitigate impacts of climate change as well as to improve energy security. This, in combination with the desire to ensure social and economic prosperity, creates a pressing need to consider the sustainability implications of future electricity generation. However, approaches to sustainability assessment differ greatly in their scope and methodology as currently there is no standardised approach. With this in mind, this paper reviews sustainability indicators that have previously been used to assess energy options and proposes a new sustainability assessment methodology based on a life cycle approach. In total, 43 indicators are proposed, addressing the techno-economic, environmental and social sustainability issues associated with energy systems. The framework has been developed primarily to address concerns associated with nuclear power in the UK, but is applicable to other energy technologies as well as to other countries.     

Whodunnit – Searching for the most important feature types signalling emotion-related user states in speech

In this article, we describe and interpret a set of acoustic and linguistic features that characterise emotional/emotion-related user states – confined to the one database processed: four classes in a German corpus of children interacting with a pet robot. To this end, we collected a very large feature vector consisting of more than 4000 features extracted at different sites. We performed extensive feature selection (Sequential Forward Floating Search) for seven acoustic and four linguistic types of features, ending up in a small number of ‘most important’ features which we try to interpret by discussing the impact of different feature and extraction types. We establish different measures of impact and discuss the mutual influence of acoustics and linguistics.