The prognostic-nutritional index in HPV-negative head and neck squamous cell carcinoma treated with upfront surgery: a multi-institutional series

Objectives. To evaluate the prognostic value of pre-treatment prognostic-nutritional index (PNI) in patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). Methods. A multi-institutional retrospective series of HPV-negative, Stages II-IVB, HNSCCs treated with upfront surgery was evaluated. Correlation of pre-operative blood markers and PNI with 5-year overall (OS) and relapse-free (RFS) survival was tested using linear and restricted cubic spline models, as appropriate. The independent prognostic effect of patient-related features was assessed with multivariable models. Results. The analysis was conducted on 542 patients. PNI ≥ 49.6 (HR = 0.52; 95% CI, 0.37-0.74) and Neutrophil-to-Lymphocyte Ratio (NLR) > 4.2 (HR = 1.58; 95% CI, 1.06-2.35) confirmed to be independent prognosticators of OS, whereas only PNI ≥ 49.6 (HR = 0.44; 95% CI, 0.29-0.66) was independently associated with RFS. Among pre-operative blood parameters, only higher values of albuninaemia and lymphocyte count (> 1.08 x 103/microL), and undetectable basophile count (= 0 103/microL) were independently associated with better OS and RFS. Conclusions. PNI represents a reliable prognostic tool providing an independent measure of pre-operative immuno-metabolic performance. Its validity is supported by the independent prognostic role of albuminaemia and lymphocyte count, from which it is derived

Designing and implementing an assay for the detection of rare and divergent NRPS and PKS clones in European, Antarctic and Cuban soils

The ever increasing microbial resistome means there is an urgent need for new antibiotics. Metagenomics is an underexploited tool in the field of drug discovery. In this study we aimed to produce a new updated assay for the discovery of biosynthetic gene clusters encoding bioactive secondary metabolites. PCR assays targeting the polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) were developed. A range of European soils were tested for their biosynthetic potential using clone libraries developed from metagenomic DNA. Results revealed a surprising number of NRPS and PKS clones with similarity to rare Actinomycetes. Many of the clones tested were phylogenetically divergent suggesting they were fragments from novel NRPS and PKS gene clusters. Soils did not appear to cluster by location but did represent NRPS and PKS clones of diverse taxonomic origin. Fosmid libraries were constructed from Cuban and Antarctic soil samples; 17 fosmids were positive for NRPS domains suggesting a hit rate of less than 1 in 10 genomes. NRPS hits had low similarities to both rare Actinobacteria and Proteobacteria; they also clustered with known antibiotic producers suggesting they may encode for pathways producing novel bioactive compounds. In conclusion we designed an assay capable of detecting divergent NRPS and PKS gene clusters from the rare biosphere; when tested on soil samples results suggest the majority of NRPS and PKS pathways and hence bioactive metabolites are yet to be discovere

New onset of loss of smell or taste in household contacts of home-isolated SARS-CoV-2-positive subjects

Purpose: To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. Methods: Cross-sectional study based on ad hoc questions. Results: Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p < 0.001). Conclusion: Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection

Microbial hitchhikers harbouring antimicrobial-resistance genes in the riverine plastisphere

Background: The widespread nature of plastic pollution has given rise to wide scientific and social concern regarding the capacity of these materials to serve as vectors for pathogenic bacteria and reservoirs for Antimicrobial Resistance Genes (ARG). In- and ex-situ incubations were used to characterise the riverine plastisphere taxonomically and functionally in order to determine whether antibiotics within the water influenced the ARG profiles in these microbiomes and how these compared to those on natural surfaces such as wood and their planktonic counterparts. Results: We show that plastics support a taxonomically distinct microbiome containing potential pathogens and ARGs. While the plastisphere was similar to those biofilms that grew on wood, they were distinct from the surrounding water microbiome. Hence, whilst potential opportunistic pathogens (i.e. Pseudomonas aeruginosa, Acinetobacter and Aeromonas) and ARG subtypes (i.e. those that confer resistance to macrolides/lincosamides, rifamycin, sulfonamides, disinfecting agents and glycopeptides) were predominant in all surface-related microbiomes, especially on weathered plastics, a completely different set of potential pathogens (i.e. Escherichia, Salmonella, Klebsiella and Streptococcus) and ARGs (i.e. aminoglycosides, tetracycline, aminocoumarin, fluoroquinolones, nitroimidazole, oxazolidinone and fosfomycin) dominated in the planktonic compartment. Our genome-centric analysis allowed the assembly of 215 Metagenome Assembled Genomes (MAGs), linking ARGs and other virulence-related genes to their host. Interestingly, a MAG belonging to Escherichia –that clearly predominated in water– harboured more ARGs and virulence factors than any other MAG, emphasising the potential virulent nature of these pathogenic-related groups. Finally, ex-situ incubations using environmentally-relevant concentrations of antibiotics increased the prevalence of their corresponding ARGs, but different riverine compartments –including plastispheres– were affected differently by each antibiotic. Conclusions: Our results provide insights into the capacity of the riverine plastisphere to harbour a distinct set of potentially pathogenic bacteria and function as a reservoir of ARGs. The environmental impact that plastics pose if they act as a reservoir for either pathogenic bacteria or ARGs is aggravated by the persistence of plastics in the environment due to their recalcitrance and buoyancy. Nevertheless, the high similarities with microbiomes growing on natural co-occurring materials and even more worrisome microbiome observed in the surrounding water highlights the urgent need to integrate the analysis of all environmental compartments when assessing risks and exposure to pathogens and ARGs in anthropogenically-impacted ecosystems. 1SQe33MjkWBo3cdx_C_SmDVideo Abstrac

Niche-adaptation in plant-associated Bacteroidetes favours specialisation in organic phosphorus mineralisation

Bacteroidetes are abundant pathogen-suppressing members of the plant microbiome that contribute prominently to rhizosphere phosphorus mobilisation, a frequent growth-limiting nutrient in this niche. However, the genetic traits underpinning their success in this niche remain largely unknown, particularly regarding their phosphorus acquisition strategies. By combining cultivation, multi-layered omics and biochemical analyses we first discovered that all plant-associated Bacteroidetes express constitutive phosphatase activity, linked to the ubiquitous possession of a unique phosphatase, PafA. For the first time, we also reveal a subset of Bacteroidetes outer membrane SusCD-like complexes, typically associated with carbon acquisition, and several TonB-dependent transporters, are induced during Pi-depletion. Furthermore, in response to phosphate depletion, the plant-associated Flavobacterium used in this study expressed many previously characterised and novel proteins targeting organic phosphorus. Collectively, these enzymes exhibited superior phosphatase activity compared to plant-associated Pseudomonas spp. Importantly, several of the novel low-Pi-inducible phosphatases and transporters, belong to the Bacteroidetes auxiliary genome and are an adaptive genomic signature of plant-associated strains. In conclusion, niche adaptation to the plant microbiome thus appears to have resulted in the acquisition of unique phosphorus scavenging loci in Bacteroidetes, enhancing their phosphorus acquisition capabilities. These traits may enable their success in the rhizosphere and also present exciting avenues to develop sustainable agriculture

New Insights into Chloramphenicol Biosynthesis in Streptomyces venezuelae ATCC 10712

Comparative genome analysis revealed seven uncharacterized genes, sven0909 to sven0915, adjacent to the previously identified chloramphenicol biosynthetic gene cluster (sven0916–sven0928) of Streptomyces venezuelae strain ATCC 10712 that was absent in a closely related Streptomyces strain that does not produce chloramphenicol. Transcriptional analysis suggested that three of these genes might be involved in chloramphenicol production, a prediction confirmed by the construction of deletion mutants. These three genes encode a cluster-associated transcriptional activator (Sven0913), a phosphopantetheinyl transferase (Sven0914), and a Na(+)/H(+) antiporter (Sven0915). Bioinformatic analysis also revealed the presence of a previously undetected gene, sven0925, embedded within the chloramphenicol biosynthetic gene cluster that appears to encode an acyl carrier protein, bringing the number of new genes likely to be involved in chloramphenicol production to four. Microarray experiments and synteny comparisons also suggest that sven0929 is part of the biosynthetic gene cluster. This has allowed us to propose an updated and revised version of the chloramphenicol biosynthetic pathway

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Introduzione a Formazione e fortuna del Tasso nella cultura della Serenissima

Presentazione degli argomenti trattati nei contributi presenti nel volume (Atti del Convegno tassiano Padova-Venezia, 10-11 novembre 1995)