The Aeromonas hydrophyla cphA gene: molecular heterogeneity among class B metallo-β-lactamases

An Aeromonas hydrophila gene, named cphA, coding for a carbapenem-hydrolyzing metallo-beta-lactamase, was cloned in Escherichia coli by screening an Aeromonas genomic library for clones able to grow on imipenem-containing medium. From sequencing data, the cloned cphA gene appeared able to code for a polypeptide of 254 amino acids whose sequence includes a potential N-terminal leader sequence for targeting the protein to the periplasmic space. These data were in agreement with the molecular mass of the original Aeromonas enzyme and of the recombinant enzyme produced in E. coli, evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude beta-lactamase preparations followed by renaturation treatment for proteins separated in the gel and localization of protein bands showing carbapenem-hydrolyzing beta-lactamase activity by a modified iodometric technique. The deduced amino acid sequence of the CphA enzyme showed regions of partial homology with both the beta-lactamase II of Bacillus cereus and the CfiA beta-lactamase of Bacteroides fragilis. Sequence homologies were more pronounced in the regions encompassing the amino acid residues known in the enzyme of B. cereus to function as ligand-binding residues for the metal cofactor. The CphA enzyme, however, appeared to share a lower degree of similarity with the two other enzymes, which, in turn, seemed more closely related to each other. These results, therefore, suggest the existence of at least two molecular subclasses within molecular class B metallo-beta-lactamases

Summary of the available molecular methods for detection of SARS-CoV-2 during the ongoing pandemic

Since early 2020, the COVID-19 pandemic has caused an excess in morbidity and mortality rates worldwide. Containment strategies rely firstly on rapid and sensitive laboratory diagnosis, with molecular detection of the viral genome in respiratory samples being the gold standard. The reliability of diagnostic protocols could be affected by SARS-CoV-2 genetic variability. In fact, mutations occurring during SARS-CoV-2 genomic evolution can involve the regions targeted by the diagnostic probes. Following a review of the literature and an in silico analysis of the most recently described virus variants (including the UK B 1.1.7 and the South Africa 501Y.V2 variants), we conclude that the described genetic variability should have minimal or no effect on the sensitivity of existing diagnostic protocols for SARS-CoV-2 genome detection. However, given the continuous emergence of new variants, the situation should be monitored in the future, and protocols including multiple targets should be preferred

The Probability of Default of Public Guaranteed Loans: Does the Financial intermediary Matter?

This paper investigates the risk of failure of loans guaranteed by public credit guarantee schemes. We analyse the determinants of the time to default of approximately 15,000 loans guaranteed by the Italian Central Guarantee Fund between 2007 and 2009. Using the Cox proportional hazards model, we test the role of the financial intermediary that requests the guarantee on a firm’s behalf, while distinguishing between banks and mutual guarantee institutions (MGIs) and controlling for a set of variables that characterise each guaranteed loan. The findings confirm that loans are more likely to default when a bank—rather than an MGI—is involved in the guarantee process. Considering some elements (e.g. age, size and sector) that affect opacity among small- and medium-sized enterprises (SMEs), banks seem to perform better than MGIs in screening and monitoring loans requested by firms in the manufacturing sector

Detection of SARS-CoV-2 N protein allelic variants by rapid high-throughput CLEIA antigen assay

We report the data obtained using an automated chemiluminescence enzyme immunoassay (CLEIA) for rapid antigen detection of SARS-CoV-2 with a number of variants

Multidrug-resistant Pseudomonas aeruginosa producing PER-1 extended-spectrum serine-beta-lactamase and VIM-2 metallo-beta-lactamase.

[No abstract available]Europena Training and Mobility of Researchers Network on Metallo-beta-Lactamases (grant no. FMRX-CT98-0232

An evidence-based multidisciplinary approach focused at creating algorithms for targeted therapy of bsis, cutis, and ciais caused by enterobacterales in critically ill adult patients

Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by Enterobacterales. The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics. A multidisciplinary team of experts (one intensive care physician, one infectious disease consultant, one clinical microbiologist and one MD clinical pharmacologist), performed several rounds of assessment to reach agreement in developing six different algorithms according to the susceptibility pattern (one each for multi-susceptible, extended-spectrum beta-lactamase-producing, AmpC beta-lactamase-producing, Klebsiella pneumoniae carba-penemase (KPC)-producing, OXA-48-producing, and Metallo-beta-lactamase (MBL)-produ-cing Enterobacterales). Whenever multiple therapeutic options were feasible, a hierarchical scale was established. Recommendations on antibiotic dosing optimization were also pro-vided. In order to retrieve evidence-based support for the therapeutic choices proposed in the algorithms, a comprehensive literature search was performed by a researcher on PubMed-MEDLINE from inception until March 2021. Quality and strength of evidence was established according to a hierarchical scale of the study design. Only articles published in English were included. It is expected that these algorithms, by allowing prompt revision of antibiotic regimens whenever feasible, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacoki-netic/pharmacodynamic optimization of antibiotic dosing regimens, may be helpful either in improving clinical outcome or in containing the spread of antimicrobial resistance

Carbapenem-resistant Pseudomonas aeruginosa with acquired bla(vim) metallo-beta-lactamase determinants, Italy.

6nonenoneROSSOLINI G.M.; RICCIO M.L.; CORNAGLIA G.; PAGANI L.; LAGATOLLA C.; SELAN L. AND FONTANA R.Rossolini, G. M.; Riccio, M. L.; Cornaglia, G.; Pagani, L.; Lagatolla, Cristina; Selan, L. AND FONTANA R

PID feedback controller used as a tactical asset allocation technique: The G.A.M. model

Abstract The objective of this paper is to illustrate a tactical asset allocation technique utilizing the PID controller. The proportional-integral-derivative (PID) controller is widely applied in most industrial processes; it has been successfully used for over 50 years and it is used by more than 95% of the plants processes. It is a robust and easily understood algorithm that can provide excellent control performance in spite of the diverse dynamic characteristics of the process plant. In finance, the process plant, controlled by the PID controller, can be represented by financial market assets forming a portfolio. More specifically, in the present work, the plant is represented by a risk-adjusted return variable. Money and portfolio managers' main target is to achieve a relevant risk-adjusted return in their managing activities. In literature and in the financial industry business, numerous kinds of return/risk ratios are commonly studied and used. The aim of this work is to perform a tactical asset allocation technique consisting in the optimization of risk adjusted return by means of asset allocation methodologies based on the PID model-free feedback control modeling procedure. The process plant does not need to be mathematically modeled: the PID control action lies in altering the portfolio asset weights, according to the PID algorithm and its parameters, Ziegler-and-Nichols-tuned, in order to approach the desired portfolio risk-adjusted return efficiently.

Biochemical characterization of the POM-1 metallo-β-lactamase from Pseudomonas otitidis

The POM-1 metallo--lactamase is a subclass B3 resident enzyme produced by Pseudomonas otitidis, a pathogen causing otic infections. The enzyme was overproduced in Escherichia coli BL21(DE3), purified by chromatography, and subjected to structural and functional analysis. The purified POM-1 is a tetrameric enzyme of broad substrate specificity with higher catalytic activities with penicillins and carbapenems than with cephalosporins