Multi-drug resistant Gram-negative bacteria: antibiotic-resistance and new treatment strategies

In this editorial, we treat the multi-drug-resistance of microorganisms such as Klebsiella pneumonia (Kp) and Acinetobacter baumanii and the issues concerning the management of these infections. Diseases caused by carbapenemase-resistant Kp (CR-Kp) represent an emerging threat worldwide due to high mortality rate and limited therapeutic options. Consequently innovative therapies have been suggested for their treatment. Colistin- based combinations are considered the milestone of the therapy for CR-Kp. They include meropenem+colistin, meropenem +colistin+tigecycline, the double carbapenem+colistin, tigecycline+colistin, colistin+gentamicin and even colistin +vancomycin. However, colistin use might be limited by its potential nephrotoxicity and resistance. Other antibiotic combinations concern the tigecycline with gentamicin, fosfomycin with aminoglycoside and ertapenem with meropenem. Thus, the double carbapenem-regimen might be considered as a suitable therapy in those subjects in whom previous antimicrobial combinations failed. New antibiotics such as ceftazidime-avibactam effective on CR-Kp and ceftolozane-tazobactam active against XDR (Extensively Drug Resistant) Pseudomonas aeruginosa are now being used in many countries. The mortality results to be lower in patients treated with antibiotic combinations than in those who underwent monotherapy. Efforts should be made by the clinicians in order to limit the widespread of these resistant microorganisms all over the world. Encouraging new solutions as bacteriophage therapy or biocides currently does not seem the right choice

Narratives of Human Trafficking: Ways of Seeing and Not Seeing the Real Survivors and Stories

The 2016 McKendy Lecture1 addressed the two grand narratives in the migration-crime-security nexus and critique their impact on our ability to see and not see real survivors and their stories of being trafficked. Focussing on the UK and female survivors, the lecture explored the crime master narrative for its construction of the social and cultural template—the official way of seeing the “right sort” of crime victim in trafficking (the VoT or modern slave). From this standpoint, anyone falling short of the template is susceptible to criminal scrutiny as someone culpable in her own exploitation. Similarly, the lecture examined the security narrative for its construction of the social and cultural template—the official way of seeing the “wrong sort” of migrant (undocumented, unskilled and racially different). Borne of political, social and cultural attitudes to UK immigration, the security narrative hides the reality of a migrant labour force without rights of citizenship or belonging. The lecture also shared stories of survivors of trafficking which illustrate how they are seen or not seen, but which survivors tell to promote their political visibility

Surface Plasmon Excitation of Second Harmonic light: Emission and Absorption

We aim to clarify the role that absorption plays in nonlinear optical processes in a variety of metallic nanostructures and show how it relates to emission and conversion efficiency. We define a figure of merit that establishes the structure's ability to either favor or impede second harmonic generation. Our findings suggest that, despite the best efforts embarked upon to enhance local fields and light coupling via plasmon excitation, nearly always the absorbed harmonic energy far surpasses the harmonic energy emitted in the far field. Qualitative and quantitative understanding of absorption processes is crucial in the evaluation of practical designs of plasmonic nanostructures for the purpose of frequency mixing

Development of a high-order parallel solver for direct and large eddy simulations of turbulent flows

Turbulence is inherent in fluid dynamics, in that laminar flows are rather the exception than the rule, hence the longstanding interest in the subject, both within the academic community and the industrial R&D laboratories. Since 1883, much progress has been made, and statistics applied to turbulence have provided understanding of the scaling laws which are peculiar to several model flows, whereas experiments have given insight on the structure of real-world flows, but, soon enough, numerical approaches to the matter have become the most promising ones, since they lay the ground for the solution of high Reynolds number unsteady Navier-Stokes equations by means of computer systems. Nevertheless, despite the exponential rise in computational capability over the last few decades, the more computer technology advances, the higher the Reynolds number sought for test-cases of industrial interest: there is a natural tendency to perform simulations as large as possible, a habit that leaves no room for wasting resources. Indeed, as the scale separation grows with Re, the reduction of wall clock times for a high-fidelity solution of desired accuracy becomes increasingly important. To achieve this task, a CFD solver should rely on the use of appropriate physical models, consistent numerical methods to discretize the equations, accurate non-dissipative numerical schemes, efficient algorithms to solve the numerics, and fast routines implementing those algorithms. Two archetypal approaches to CFD are direct and large-eddy simulation (DNS and LES respectively), which profoundly differ in several aspects but are both “eddy-resolving” methods, meant to resolve the structures of the flow-field with the highest possible accuracy and putting in as little spurious dissipation as possible. These two requirements of accurate resolution of scales, and energy conservation, should be addressed by any numerical method, since they are essential to many real-world fluid flows of industrial interest. As a consequence, high order numerical schemes, and compact schemes among them, have received much consideration, since they address both goals, at the cost of a lower ease of application of the boundary condition, and a higher computational cost. The latter problem is tackled with parallel computing, which also allows to take advantage of the currently available computer power at the best possible extent. The research activity conducted by the present author has concerned the development, from scratch, of a three-dimensional, unsteady, incompressible Navier-Stokes parallel solver, which uses an advanced algorithm for the process-wise solution of the linear systems arising from the application of high order compact finite difference schemes, and hinges upon a three-dimensional decomposition of the cartesian computational space. The code is written in modern Fortran 2003 — plus a few features which are unique to the 2008 standard — and is parallelized through the use of MPI 3.1 standard’s advanced routines, as implemented by the OpenMPI library project. The coding was carried out with the objective of creating an original CFD high-order parallel solver which is maintainable and extendable, of course within a well-defined range of possibilities. With this main priority being outlined, particular attention was paid to several key concepts: modularity and readability of the source code and, in turn, its reusability; ease of implementation of virtually any new explicit or implicit finite difference scheme; modern programming style and avoidance of deprecated old legacy Fortran constructs and features, so that the world wide web is a reliable and active means to the quick solution of coding problems arising from the implementation of new modules in the code; last but not least, thorough comments, especially in critical sections of the code, explaining motives and possible expected weak links. Design, production, and documentation of a program from scratch is almost never complete. This is certainly true for the present effort. The method and the code are verified against the full three-dimensional Lid-Driven Cavity and Taylor-Green Vortex flows. The latter test is used also for the assessment of scalability and parallel efficiency

Antibiotic susceptibility, heteroresistance, and updated treatment strategies in helicobacter pylori infection

In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals.In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals

Synuclein expression in the lizard Anolis carolinensis

The synuclein (syn) family comprises three proteins: alpha-, beta- and gamma-syns. In humans, they are involved in neurodegenerative diseases such as Parkinson's disease and in tumors. Members of the syn family were sequenced in representative species of all vertebrates and the comparative analysis of amino acid sequences suggests that syns are evolutionarily conserved, but information about their expression in vertebrate lineages is still scarce and completely lacking in reptiles. In this study, the expression of genes coding for alpha-, beta- and gamma-syns was analyzed in the green lizard Anolis carolinensis by semiquantitative RT-PCR and Western blot. Results demonstrate good expression levels of the three syns in the lizard nervous system, similarly to human syns. This, together with the high identity between lizard and human syns, suggests that these proteins fulfill evolutionarily conserved functions. However, differences between lizard and humans in the expression of syn variants (two different variants of gamma-syn were detected in A. carolinensis) and differences in some amino acids in key positions for the regulation of protein conformation and affinity for lipid and metal ions also suggest that these proteins may have acquired different functional specializations in the two lineages

Autism spectrum disorders and intestinal microbiota

Through extensive microbial-mammalian co-metabolism, the intestinal microbiota have evolved to exert a marked influence on health and disease via gut-brain-microbiota interactions. In this addendum, we summarize the findings of our recent study on the fecal microbiota and metabolomes of children with pervasive developmental disorder–not otherwise specified (PDD-NOS) or autism (AD) compared with healthy children (HC). Children with PDD-NOS or AD have altered fecal microbiota and metabolomes (including neurotransmitter molecules). We hypothesize that the degree of microbial alteration correlates with the severity of the disease since fecal microbiota and metabolomes alterations were higher in children with PDD-NOS and, especially, AD compared to HC. Our study indicates that the levels of free amino acids (FAA) and volatile organic compounds (VOC) differ in AD subjects compared to children with PDD-NOS, who are more similar to HC. Finally, we propose a new perspective on the implications for the interaction between intestinal microbiota and AD