Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease

The aim of the present study was to determine the profile of different inflammatory molecules in serum and cerebrospinal fluid (CSF) during invasive meningococcal disease (IMD). Their relationship with IMD severity was also assessed. A cohort of 12 patients with IMD was investigated. Paired serum and CSF samples were obtained at the time of diagnostic and follow-up lumbar puncture and were examined using Luminex® analysis. IMD severity correlated with serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) on admission. Furthermore, the CSF levels of IL-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein-1β (MIP-1β), and monocyte chemoattractant protein-1 (MCP-1) were significantly higher than their respective serum levels. The strongest correlations were found between serum concentrations of IL-1β and IL-1ra, IL-6, IL-8, and MIP-1β, whereas the strongest correlations in CSF were found between endotoxin and IL-8, IL-17, MIP-1β, and MCP-1. As was expected, the concentrations of inflammatory molecules in both serum and CSF significantly decreased after antibiotic treatment. With regard to kinetics, a severe course of IMD correlated positively with rapid declines of CSF IL-6 and cortisol levels. Sequential multiple analyses revealed patterns of inflammatory responses that were associated with the severity of IMD, as well as with the compartmentalization and kinetics of the immune reaction

‘Money probably has something to do with my life’: discourse and materiality in the working lives of start-up entrepreneurs

This article contributes to an understanding of work-intensive entrepreneurial lives as part of analysing the intensification of work in society. It offers an empirical extension of Foucauldian analyses which attribute commitment to work to the influence of neoliberal enterprise discourse while often neglecting the material conditions of entrepreneurial work. The article draws on moderate constructionism and materialist discourse analysis to offer an account that pays attention to discourse and material realities. This ethnographic study shows how participants evoked norms of enterprise discourse to explain their commitment to work. However, they also understood these norms to be fundamentally shaped by their material conditions. The major contribution of the paper is to show that the interpenetration of discursive norms with the investment logic of enterprise tends to displace boundaries between work and personal life and shift temporal arrangements of work from work-life ‘balance’ to prospects of free time in the imagined future

Conifers phytochemicals: A valuable forest with therapeutic potential

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.This research was funded by University of Hradec Kralove (Faculty of Science VT 2019-2021)

Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer's Disease Therapy

In this communication, wereport the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer¿s disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 M), with Ki value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation.R.A., M.S., P.B., and K.M. were supported by European Regional Development Fund/European Social Fund (ERDF/ESF, project PharmaBrain, no. CZ.02.1.01/0.0/0.0/16_025/0007444), University of Hradec Kralove (no. SV2113-2019, VT2019-2021), and EU COST action CA15135 MuTaLig. J.M.C. thanks Ministerio de Economía (MINECO, SAF2015-65586-R) and Universidad Camilo José Cela (UCJC, grants UCJC 2020-03, and UCJC 2020-33) for support

A comparison of the neuroprotective efficacy of newly developed oximes (K117, K127) and currently available oxime (obidoxime) in tabun-poisoned rats

The potency of newly developed bispyridinium compounds (K117, K127) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oxime (obidoxime) using functional observational battery. The neuroprotective effects of atropine alone and atropine combined with one of three bispyridinium oximes (K117, K127, obidoxime) on rats poisoned with tabun at a sublethal dose (180 μg/kg i.m.; 80% of LD50 value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 24 h following tabun challenge while one tabun-poisoned rats died within 24 h after tabun poisoning when the rats were treated with atropine alone. Newly developed oxime K127 combined with atropine was the most effective in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Nevertheless, the differences of neuroprotective efficacy between K127 and obidoxime are not sufficient to replace obidoxime by K127 for the treatment of acute tabun poisonings

Description of <i>Acinetobacter venetianus ex</i> Di Cello <i>et al.</i> 1997 sp. nov.

The name ‘Acinetobacter venetianus’ has been used previously to designate three marine hydrocarbon-degrading Acinetobacter strains, of which strain RAG-1 (=ATCC 31012) has industrial applications for the production of the bioemulsifier emulsan. However, to date, the name of this taxon has not been validly published. In this study, five strains were examined to corroborate the delineation of this taxon by means of phenotypic characterization, DNA–DNA hybridization, selective restriction fragment amplification (AFLP), amplified rDNA restriction analysis (ARDRA), rpoB gene sequence analysis and tRNA intergenic spacer length polymorphism analysis (tDNA-PCR) and to emend the description of ‘Acinetobacter venetianus’ (ex Di Cello et al. 1997 ). AFLP analysis showed that the five strains formed a tight cluster at 56.8±5.0 % genomic relatedness that was separated from strains of other haemolytic species of the genus Acinetobacter and from the type and reference strains of other Acinetobacter species at ≤27 % relatedness, indicating the distinctiveness of the novel strains. The strains were haemolytic and able to grow on citrate (Simmons), L-histidine and malonate. The strains did not oxidize D-glucose or utilize DL-lactate or L-aspartate. The G+C contents of strains RAG-1 and of VE-C3 were 43.9 % and 43.6 mol%, respectively. The novel strains could be recognized by a characteristic ARDRA pattern (CfoI 1, AluI 3, MboI 2, RsaI 2, MspI 3). The consensus tDNA-PCR pattern for the five strains consisted of amplified fragments of 87.9, 100.2, 134.6 and 248.5 bp and was indistinguishable from that of strains of Acinetobacter genomic species 14BJ. The five strains represent a novel species for which the name Acinetobacter venetianus sp. nov. is proposed. The type strain is RAG-1T (=ATCC 31012T=CCUG 45561T=LMG 19082T=LUH 3904T=NIPH 1925T)

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization