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The impact of thrombocytopenia on postoperative bleeding and other major adverse events after cardiac surgery is unclear. This issue was investigated in a series of patients who underwent isolated coronary artery bypass grafting (CABG) from the prospective, multicenter E-CABG registry. Preoperative thrombocytopenia was defined as preoperative platelet count

We report the use of a new multiplex Real-Time PCR platform to simultaneously identify 24 pathogens and 3 antimicrobial-resistance genes directly from respiratory samples of COVID-19 patients. Results were compared to culture-based diagnosis. Secondary infections were detected in 60% of COVID-19 patients by molecular analysis and 73% by microbiological assays, with no significant differences in accuracy, indicating Gram-negative bacteria as the predominant species. Among fungal superinfections, Aspergillus spp. were detected by both methods in more than 7% of COVID-19 patients. Oxacillin-resistant S. aureus and carbapenem-resistant K. pneumoniae were highlighted by both methods. Secondary microbial infections in SARS-CoV-2 patients are associated with poor outcomes and an increased risk of death. Since PCR-based tests significantly reduce the turnaround time to 4 hours and 30 minutes (compared to 48 hours for microbial culture), we strongly support the routine use of molecular techniques, in conjunction with microbiological analysis, to identify co/secondary infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Italy has been the first European Country dealing with SARS-CoV-2, whose diffusion on the territory has not been homogeneous. Among Italian regions, Sardinia represented one of the lowest incidence areas, likely due to its insular nature. Despite this, the impact of insularity on SARS-CoV-2 genetic diversity has not been comprehensively described., Methods: In the present study, we performed the high throughput sequencing of 888 SARS-CoV-2 genomes collected in Sardinia during the first 23 months of pandemics. In addition, 1439 high-coverage SARS-CoV-2 genomes circulating in Sardinia along three years (December 2019 - January 2023) were downloaded from GISAID, for a total of 2327 viral sequences that were characterized in terms of phylogeny and genomic diversity., Results: Overall, COVID-19 pandemic in Sardinia showed substantial differences with respect to the national panorama, with additional peaks of infections and uncommon lineages that reflects the national and regional policies of re-opening and the subsequent touristic arrivals. Sardinia has been interested by the circulation of at least 87 SARS-CoV-2 lineages, including some that were poorly represented at national and European level, likely linked to multiple importation events. The relative frequency of Sardinian SARS-CoV-2 lineages has been compared to other Mediterranean Islands, revealing a unique composition., Conclusions: The genomic diversity of SARS-CoV-2 in Sardinia has been shaped by a complex interplay of insular geography, low population density, and touristic arrivals, leading on the one side to the importation of lineages remaining rare at the national level, and resulting on the other side in the delayed entry of otherwise common variants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species 1 . Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe 1,2 . To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia BCE, respectively; for P. vivax, this evidence pre-dates textual references by several millennia 3 . Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago., (© 2024. The Author(s).)

Introduction: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs., Methods: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated., Results: Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new β-lactam/β-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%)., Conclusions: This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

While platinum(II)-based drugs continue to be employed in cancer treatments, the escalating occurrence of severe side effects has spurred researchers to explore novel sources for potential therapeutic agents. Notably, cobalt(III) has emerged as a subject of considerable interest due to its ubiquitous role in human physiology. Several studies investigating the anticancer effects of Salphen complexes derived from cobalt(III) have unveiled intriguing antiproliferative properties. In a bid to enhance our understanding of this class of compounds, we synthesized and characterized two novel half Salphen cobalt(III) complexes. Both compounds exhibited notable stability, even in the presence of physiologically relevant concentrations of glutathione. The application of spectroscopic and computational methodologies unravelled their interactions with duplex and G4-DNAs, suggesting an external binding affinity for these structures, with preliminary indications of selectivity trends. Importantly, antiproliferative assays conducted on 3D cultured SW-1353 cancer cells unveiled a compelling anticancer activity at low micromolar concentrations, underscoring the potential therapeutic efficacy of this novel class of cobalt(III) complexes.

Introduction: A COVID-19 outbreak occurred at the end of October 2021 among pilgrims returning from Medjugorje (Bosnia and Herzegovina)., Methodology: Whole genome sequencing (WGS) of SARS-CoV-2, epidemiological data, and phylogenetic analysis were used to reconstruct outbreak dynamics., Results: The results suggest that only in one case, associated with the SARS-CoV-2 sub-lineage AY.9.2, it is possible to trace back the place of contagion to Medjugorje, while the other cases were likely to be acquired in the country of origin., Conclusions: The combined use of phylogenetic data derived from WGS, and epidemiological data allowed us to study epidemic dynamics and to formulate a possible hypothesis on the place of exposure to SARS-CoV-2. The identification of different sub-lineages of the SARS-CoV-2 Delta variant also suggested that different chains of transmission contributed to the outbreak., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Alessandra Lo Presti, Salvatore Rubino, Gabriele Ibba, Luigina Ambrosio, Angela Di Martino, Federica Ferraro, Alessia Rapiti, Francesco Maraglino, Emanuela Maria Frisicale, Giovanni Rezza, Flavia Angioj, Sergio Uzzau, Maria Luciana Contini, Stefania Manca, Ferdinando Coghe, Germano Orrù, Anna Teresa Palamara, Paola Stefanelli, the AOUSS COVID team.)

Aims: In this study, five essential oils (EOs) from different species of Lavandula hybrida abrialis , for Lavandula hybrida R.C., Lavandula hybrida 'super A', Lavandula hybrida 'super Z' and Lavandula vera and its hybrids Lavender were evaluated against 26 dust-isolated fungal strains from North Africa., Methods and Results: The composition of the different EOs was determined from volume to dry weight. The photochemical analyses were performed via gas chromatography (GC). The cytotoxic effect of five lavender EOs on human epithelial colorectal adenocarcinoma cells (Caco-2) cell line was done. A total of 26 strains of filamentous fungi including Aspergillus spp. , Botrytis cinerea , Ceriporia spp. , Fusarium spp. and Penicillium glabrum were isolated from sand dust samples via molecular diagnostic tool of PCR. Fungal strains with the lowest minimal lethal concentration (MLC) were Penicillium glabrum, Ceriporia spp. and a strain of Aspergillus spp., Conclusions: More studies are needed to verify the activity of this EO against more different fungal species, and determine the active ingredients. Significance and impact of study: MIC of the antifungal efficacy relating to EOs was evaluated. The EOs tests showed no cytotoxic effect at very low concentrations, ranging from 0.03% (IC 50 0.9132 mg/mL) ( L. hybrid Abrialis) to 0.001% (IC 50 1.631 mg/mL) ( L. hybrid R.C.).

Background: The goal of this study was to monitor the microbial biodiversity in beach sand that is heavily visited by tourists during the summer, and to determinate whether the high presence of bathers (around 5000 per day) can modify sand microbial composition., Methods: Between 2016 and 2020, 150 sand samples were collected from nine different points at La Pelosa beach in Sardinia, Italy. Non-culturing methods were used; DNA extraction and meta-barcode sequencing were performed. All samples were analyzed with sequencing methods for 16S and ITS sequences., Results: Fungal genera differ on the three beaches and in the winter/summer zones. The ITS sequence showed the most common presence of Candida during summer and Paradendryphiella in the winter. The greatest diversity was found in the dune during winter, while in other parts of the beach, there are differences between bacteria and fungi, particularly in the wash zone during the winter, with high diversity for 16S sequences but low diversity for ITS sequences., Conclusions: It appears reasonable that the sands, even on non-urban beaches, should be included in health monitoring programs in addition to the waters, and that access to them should be regulated by limiting the number of bathers with the aim of reducing the presence of pathogenic fungal species.

Purpose: There is a growing body of literature documenting glioma heterogeneity in terms of radiographic, histologic, molecular, and genetic characteristics. Incomplete spatial specification of intraoperative tumor samples may contribute to variability in the results of pathological and biological investigations. We have developed a system, termed geo-tagging, for routine intraoperative linkage of each tumor sample to its location via neuronavigation., Methods: This is a single-institution, IRB approved, prospective database of undergoing clinically indicated surgery. We evaluated relevant factors affecting data collection by this registry, including tumor and surgical factors (e.g. tumor volume, location, grade and surgeon)., Results: Over a 2-year period, 487 patients underwent craniotomy for an intra-axial tumor. Of those, 214 underwent surgery for a newly diagnosed or recurrent glioma. There was significant variation in the average number of samples collected per registered case, with a range of samples from 2.53 to 4.75 per tumor type. Histology and grade impacted on sampling with a range of 2.0 samples per tumor in Grade four, IDH-WT gliomas to 4.5 samples in grade four, IDH-mutant gliomas. The range of cases with sampling per surgeon was 6 to 99 with a mean of 47.6 cases and there was a statistically significant differences between surgeons. Tumor grade did not have a statistically significant impact on number of samples per case. No significant correlation was found between the number of samples collected and enhancing tumor volume, EOR, or volume of tumor resected., Conclusion: We are using the results of this analysis to develop a prospective sample collection protocol., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The chemical shift (CS) values obtained by 1 H NMR spectroscopy for the hydrogen atoms of a tetradentate N 2 O 2 -substituted Salphen ligand (H 2 L1 ) are differently shifted in its complexes of nickel(II), palladium(II), platinum(II), and zinc(II), all bearing the same charge on the metal ions. To rationalize the observed trends, DFT calculations have been performed in the implicit d 6 -DMSO solvent in terms of the electronic effects induced by the metal ion and of the nature and strength of the metal-N and metal-O bonds. Overall, the results obtained point out that, in the complexes involving group 10 elements, the CS values show the greater shift when considering the two hydrogen atoms at a shorter distance from the coordinated metal center and follow the decreasing metal charge in the order Ni > Pd > Pt. This trend suggests a more covalent character of the ligand-metal bonds with the increase of the metal atomic number. Furthermore, a slightly poorer agreement between experimental and calculated data is observed in the presence of the nickel(II) ion. Such discrepancy is explained by the formation of stacked oligomers, aimed at minimizing the repulsive interactions with the polar DMSO solvent.

Globally, antibiotic-resistant Klebsiella spp. cause healthcare-associated infections with high mortality rates, and the rise of hypervirulent Klebsiella pneumoniae (hv Kp ) poses a significant threat to human health linked to community-acquired infections and increasing non-susceptibility. We investigated the phenotypic and genetic features of 36 Klebsiella isolates recovered from invasive infections at Hospital Central of Maputo in Mozambique during one year. The majority of the isolates displayed multidrug resistance (MDR) (29/36) to cephalosporins, gentamicin, ciprofloxacin, and trimethoprim-sulfamethoxazole but retained susceptibility to amikacin, carbapenems, and colistin. Most isolates were ESBLs-producing (28/36), predominantly carrying the bla CTX-M-15 and other beta-lactamase genes ( bla SHV , bla TEM-1 , and bla OXA-1 ). Among the 16 genomes sequenced, multiple resistance genes from different antibiotic classes were identified, with bla CTX-M-15 , mostly in the IS Ecp1 - bla CTX-M-15 - orf477 genetic environment, co-existing with bla TEM-1 and aac(3)-IIa in five isolates. Our results highlight the presence of polyclonal MDR ESBL-producing K. pneumoniae from eight sequence types (ST), mostly harbouring distinct yersiniabactin within the conjugative integrative element (ICE). Further, we identified susceptible hv Kp ST23, O1-K1-type isolates carrying yersiniabactin ( ybt1 /ICEKp10), colibactin, salmochelin, aerobactin, and hypermucoid locus ( rmpADC ), associated with severe infections in humans. These findings are worrying and underline the importance of implementing surveillance strategies to avoid the risk of the emergence of the most threatening MDR hv Kp .

Objective: This study seeks to assess rheumatology fellows' (RFs') and program directors' (PDs') interests in different educational tools and methods and to facilitate curriculum development for reproductive health related to rheumatic disease., Methods: Constructs were conceptualized in four dimensions: 1) RF and PD confidence in their current curriculum relating to the American College of Rheumatology (ACR) Reproductive Health Guidelines (RHGs), 2) personal interest in this topic, 3) opinions of the importance of this topic, and 4) interest in a range of learning materials and educational experiences. The final survey was distributed to 753 RFs and 179 PDs in the United States using the ACR Committee on Training and Workforce email list., Results: Response rates were 13% (n = 98) for RFs and 25% (n = 44) for PDs. Both groups indicated more interest in the topic than confidence in their curriculum and rated summary sheets, question banks, didactics, and online modules higher than nine other educational tools or methods. Despite interest in the topic, 38% of RF respondents and 24% of PD respondents were unaware of the recently published ACR RHGs., Conclusion: RFs and PDs consider reproductive health very important and report high personal interest in this topic. In contrast, both groups indicated lower confidence in current curricula, and substantial proportions of both groups were unaware of recently published guidelines. RFs' and PDs' interests in specific educational modalities are aligned. Curriculum development efforts should prioritize summary sheets, question banks, didactics, and online modules. Efforts are needed to address the educational needs of practicing rheumatologists and other professionals caring for patients with rheumatic disease., (© 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The occupational risk of operators using display screen equipment (DSE) is usually evaluated according to the extent of time spent in active operator-DSE interactions. Risk assessment is based on activity data collected through questionnaires. We evaluated an original and innovative system that can objectively assess active operator-DSE interactions by collecting electrical impulses generated by the activation of mouse, keyboard and a camera that collects attentive eye-screen fixation. The main aim of this study was to evaluate the system's performance on an employee sample involved in the task of active reading and copying at a DSE workstation connected to the system. In the context of mandatory health surveillance at work, we enrolled 38 DSE operators with normal neuropsychological and eye assessments who were required to complete two predefined reading and writing tasks. The obtained results show that the system is able to collect activity data derived from operator-DSE interactions through screen fixation, keyboard tapping and mouse handling. In the copying task, the session duration as recorded by the system was highly related to the screen fixation time. In the copying task, mouse and keyboard activities were more strongly related to session duration than screen fixation. For the copying task, it was also possible to obtain individual profiles of operator-DSE interactions while performing the same standardized tasks. Collected data can allow an objective evaluation of active time spent by DSE operators at their workstations, thus allowing a more accurate occupational health risk assessment and management. Prospective analysis of individual operator-DSE interaction profiles can favor the setup of targeted preventive and organizational interventions from an of even wider worker wellbeing perspective.

DNA G-rich sequences can organize in four-stranded structures called G-quadruplexes (G4s). These motifs are enriched in significant sites within the human genomes, including telomeres and promoters of cancer related genes. For instance, KIT proto-oncogene promoter, associated with diverse cancers, contains three adjacent G4 units, namely Kit2, SP, and Kit1. Aiming at finding new and selective G-quadruplex binders, we have synthesized and characterized five non-charged metal complexes of Pt(II), Pd(II), Ni(II), Cu(II) and Zn(II) of a chlorine substituted Salphen ligand. The crystal structure of the Pt(II) and Pd(II) complexes was determined by XRPD. FRET measurements indicated that Pt(II) and Pd(II) compounds stabilize Kit1 and Kit2 G4s but not SP, telomeric and double stranded DNA. Spectroscopic investigations (UV-Vis, circular dichroism and fluorescence) suggested the Cu(II) complex as the most G4-selective compound. Interestingly, docking simulations indicate that the synthesized compounds fit groove binding pockets of both Kit1 and Kit2 G4s. Moreover, they exhibited dose-dependent cytotoxic activity in MCF-7, HepG2 and HeLa cancer cells.

Rare information is available on clinical Enterococcus faecium encountered in Sardinia, Italy. This study investigated the antimicrobial susceptibility profiles and genotypic characteristics of E. faecium isolated at the University Hospital of Sassari, Italy, using the Vitek2 system and PCR, MLST, or WGS. Vitek2 revealed two VanB-type vancomycin-resistant Enterococcus faecium (VREfm) isolates (MICs mg/L = 8 and ≥32) but failed to detect vancomycin resistance in one isolate (MIC mg/L ≤ 1) despite positive genotypic confirmation of vanB gene, which proved to be vancomycin resistant by additional phenotypic methods (MICs mg/L = 8). This vanB isolate was able to increase its vancomycin MIC after exposure to vancomycin, unlike the "classic" occult vanB -carrying E. faecium , becoming detectable by Vitek 2 (MICs mg/L ≥ 32). All three E. faecium had highly mutated vanB 2 operons, as part of a chromosomally integrated Tn 1549 transposon, with common missense mutations in VanH and VanB 2 resistance proteins and specific missense mutations in the VanW accessory protein. There were additional missense mutations in VanS, VanH, and VanB proteins in the vanB 2 -carrying VREfm isolates compared to Vitek2. The molecular typing revealed a polyclonal hospital-associated E. faecium population from Clade A1, and that vanB 2 -VREfm, and nearly half of vancomycin-susceptible E. faecium (VSEfm) analyzed, belonged to ST117. Based on core genome-MLST, ST117 strains had different clonal types (CT), excluding nosocomial transmission of specific CT. Detecting vanB 2 -carrying VREfm isolates by Vitek2 may be problematic, and alternative methods are needed to prevent therapeutic failure and spread.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide-bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu's parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of <1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate that Ryugu's parent body formed ~2 million years after the beginning of Solar System formation.

Extended-spectrum β-lactamase (ESBL)-producing extraintestinal pathogenic Escherichia coli (ExPEC), particularly high-risk lineages, are responsible for severe infections and increased mortality and hospital costs worldwide, with a major burden in low-income countries. Here we determined the antimicrobial susceptibility and performed whole-genome sequencing of E. coli isolates from extraintestinal infections of patients during 2017-2018 at Maputo Central Hospital (Mozambique). Multidrug resistance was displayed by 71% of isolates (17/24). All isolates resistant to cefotaxime and ceftazidime were positive for ESBL genes (16/24; 67%) and were co-resistant to amoxicillin/clavulanate (14/16; 88%), piperacillin/tazobactam (8/16; 50%), gentamicin (12/16; 75%), trimethoprim/sulfamethoxazole (15/16; 94%) and ciprofloxacin (11/16; 69%). Several major high-risk ExPEC lineages were identified, such as H30Rx-ST131, fimH41-ST131, H24Rx-ST410, ST617, ST361 and ST69 harbouring bla CTX-M-15 , and H30R-ST131, ST38 and ST457 carrying bla CTX-M-27 . Dissemination of CTX-M transposition units (ISEcp1-bla CTX-M-15 -orf477 and ISEcp1-bla CTX-M-27 -IS903B) among different sequence types could be occurring through the mobility of IncF plasmids. Additionally, all H24Rx-ST410 isolates carried ISEcp1-mediated bla CMY-2 AmpC and specific mutations in PBP3/OmpC proteins, potentially contributing to carbapenem resistance even in the absence of carbapenemase genes. Genome analysis highlighted a high assortment of ExPEC/UPEC virulence-associated genes mainly involved in adhesion, invasion, iron uptake and secretory systems among isolates, and an ExPEC/EAEC hybrid pathotype (fimH27-ST131&#95;O18-ac:H4) showing the highest virulence gene content. cgMLST showed clonality and closely related isolates, particularly among ST131 and ST410, suggesting hospital-acquired infections and long-term ward persistence. Our study provides new insights into ExPEC clones, urging measures to prevent and contain their diffusion in this hospital and Mozambique., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this work, we observed an increased presence of antibodies (Abs) against type I interferon (IFN-I) in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to non-ICU COVID-19 patients and healthy control (HC) subjects. Human endogenous retrovirus W (HERV-W) can reactivate after viral infection; therefore, we also investigated the presence of antibodies against HERV-W envelope (HERV-W-env)-derived epitopes. A total of 113 subjects (41 female and 72 male subjects) were analyzed. A significant difference in autoantibodies against IFN-α, IFN-ω, and HERV-W was observed between HCs and ICU patients; indeed, the latter have higher levels of autoantibodies against IFN-α, IFN-ω, and HERV-W than subjects with mild COVID-19 and HCs. Neutralizing anti-IFN-I autoantibodies may affect the ability of IFN-I to bind to the type I interferon receptor (IFNAR), blocking the activation of the antiviral response. IMPORTANCE In this work, we report the increased presence of IFN autoantibodies in correlation with HERV-W-env autoantibodies in ICU COVID-19 patients. The novelty of the results is in the association of these IFN autoantibodies with autoantibodies against HERV-W-env, a protein recently discovered to be overexpressed in lymphocytes of COVID-19 patients and correlated with severe disease and pneumonia. Type I IFNs are part of a complex cross-regulatory network; however, in a small percentage of cases, the increase in autoantibodies against these proteins may lead to damage to the host instead of protection against infectious diseases.

Eumycetoma is a chronic debilitating fungal disease endemic to tropical and subtropical regions, with Sudan featuring the highest eumycetoma incidence. Among the 50 species of fungi most commonly associated with eumycetoma Madurella mycetomatis (M. mycetomatis) is often referenced as the most common pathogen. However, there is an enormous knowledge gap related to this neglected disease and its pathogenesis, epidemiological features, and host-specific factors that could contribute to either the host susceptibility and resistance. In this study, we were able to utilize a metagenomic approach and samples collected from clinical black grains (BG) and familiar household environments aimed to assay both the habitat of eumycetoma-associated fungi and its possible connection with eumycetoma patients living in two different eumycetoma endemic villages within the White Nile State of Sudan. DNA sequencing targeting the fungal ITS2 domain was performed on soil, animal dung, housing walls and roofs, and Acacia-species thorn samples and compared with culture-dependent methods of fungal isolation. Additionally, we compared the soil samples obtained in the endemic zone with that from non-endemic zones, including Wagga village in Kassala State and Port Sudan suburb in Port Sudan State. Overall, a total of 392 Amplicon Sequence Variants (ASVs) were detected by ITS2 metagenomics Eumycetoma causative organisms accounted for 10% of total ASVs which included 11 genera: Exserohilum (2%), Aspergillus (1.7%), Curvularia (1%), Alternaria (0.9%), Madurella (0.5%), Fusarium (0.4%), Cladosporium (0.2%) Exophiala (0.15%), and, in a lesser extent, Microascus (0.05%) Bipolaris and Acremonium (0.01%) for each. Only five genera were identified by culture method, which included Fusarium (29%), Aspergillus (28%), Alternaria (2.5%), Bipolaris (1.6%), and Chaetomium (0.8%). M. mycetomatis was detected within all the studied patients' houses, accounting for 0.7% of total sequences. It was the first common eumycetoma-associated agent detected in soil samples and the third common in the dung and wall samples. In contrast, it was not detected in the roof or thorn samples nor in the soils from non-endemic regions. Exserohilum rostratum, Aspergillus spp and Cladosporium spp were detected in all samples. M. mycetomatis and other eumycetoma-associated fungal identified in the patients' black grains (BG) samples by metagenomics were identified in the environmental samples. Only Acremonium alternatum and Falciformispora senegalensis, responsible for eumycetoma in two patients were not detected, suggesting the infections in these patients happened outside these endemic areas. The soil, animal dung, and houses built from the same soil and dung are the main risk factors for M. mycetomatis infection in these endemic villages. Furthermore, the poor hygienic and environmental conditions, walking barefooted, and the presence of animals within the houses increase the risk of M. mycetomatis and other fungi causing eumycetoma., Competing Interests: The authors have declared that no competing interests exist.

Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lynes, Flores-Milan, Rubino, Arrington, Macaulay, Liu, Beer-Furlan, Tran, Vogelbaum and Etame.)

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome continue to threaten the global landscape of the coronavirus disease 2019 (COVID-19) pandemic. The Omicron variant (B.1.1.529) rapidly displaced previous 'variants of concern' (VoC) in 2021 due to its high rate of transmissibility and multitude of mutations. This global influx of infections saturated healthcare systems, overwhelmed testing capacity and case reporting, and increased the COVID-19 death toll. Global health leaders are now being faced with the most transmissible COVID-19 variants yet, the Omicron sublineages BA.4 and BA.5, which contain additional spike protein (S) mutations from previous Omicron and VoC serotypes. With universally observed antibody waning, increasing vaccine-variant mismatch, and resuming international travel, the stage is set for unprecedented levels of breakthrough infections and superspreading events. In this paper, we raise awareness to these novel variants and provide context for the high likelihood of an upcoming wave of infection capable of inflicting significant disease burden on a global scale., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Benjamin Hewins, Christopher Richardson, Salvatore Rubino, Alyson Kelvin, Ali Toloue Ostadgavahi, David J Kelvin.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In December 2019, a novel coronavirus emerged in Wuhan, China, rapidly spreading into a global pandemic. Italy was the first European country to experience SARS-CoV-2 epidemic, and one of the most severely affected during the first wave of diffusion. In contrast to the general restriction of people movements in Europe, the number of migrants arriving at Italian borders via the Mediterranean Sea route in the summer of 2020 had increased dramatically, representing a possible, uncontrolled source for the introduction of novel SARS-CoV-2 variants. Importantly, most of the migrants came from African countries showing limited SARS-CoV-2 epidemiological surveillance. In this study, we characterized the SARS-CoV-2 genome isolated from an asymptomatic migrant arrived in Sardinia via the Mediterranean route in September 2020, in comparison with SARS-CoV-2 isolates arrived in Sicily through the Libyan migration route; with SARS-CoV-2 isolates circulating in Sardinia during 2020; and with viral genomes reported in African countries during the same summer. Results showed that our sequence is not phylogenetically related to isolates from migrants arriving in Sicily, nor to isolates circulating in Sardinia territory, having greater similarity to SARS-CoV-2 genomes reported in countries known for being sites of migrant embarkation to Italy. This is in line with the hypothesis that most SARS-CoV-2 infections among migrants have been acquired prior to embarking to Italy, possibly during the travel to or the stay in crowded Libyan immigrant camps. Overall, these observations underline the importance of dedicated SARS-CoV-2 surveillance of migrants arriving in Italy and in Europe through the Mediterranean routes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grandi, Paglietti, Cusano, Ibba, Lai, Piu, Angioj, Serra, Kelvin, Tramontano and Rubino.)

Brain metastases are the most common form of brain cancer. Increasing knowledge of primary tumor biology, actionable molecular targets and continued improvements in systemic and radiotherapy regimens have helped improve survival but necessitate multidisciplinary collaboration between neurosurgical, medical and radiation oncologists. In this review, we will discuss the advances of targeted therapies to date and discuss findings of studies investigating the synergy between these therapies and stereotactic radiosurgery for non-small cell lung cancer, breast cancer, melanoma, and renal cell carcinoma brain metastases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rubino, Oliver, Tran, Vogelbaum, Forsyth, Yu, Ahmed and Etame.)

Purpose: The purpose of this study is to review the neonatal and early childhood course of children who were treated with intravitreal bevacizumab for APROP and identify any long term limitations these children face years after treatment., Methods: This retrospective consecutive case series reviewed both ophthalmologic and pediatric medical records to determine ocular and neurologic function following treatment with a single injection of intravitreal bevacizumab (IVB) for APROP. Patient records were reviewed to identify the gestational age, average birth weight, gender, post-menstrual age (PMA) at the time of injection, regression status, rescue therapy events, final visual acuity, final refraction, ophthalmologic diagnoses and complications, neurologic diagnoses, and duration of follow up., Results: The study included 43 eyes from 13 male and 9 female children. The average gestational age was 24 weeks and average birth weight was 625.2 grams. The average follow-up was 4.08 years (range: 1.85-7.36 years). The average PMA at time of bevacizumab injection was 35.59 weeks. Thirty-five eyes eventually received laser photocoagulation at an average PMA of 53.17 weeks. All eyes in this study demonstrated regression without progression to retinal detachment. At last follow up, 67% (29/43) of eyes were able to discern letters or shapes, with an average visual acuity of 20/37. 16 (72%) children were diagnosed with perinatal neurological disorders. 59% ( n = 13) developed chronic neurological impairment, 77% ( n = 10) of whom developed neurodevelopmental delay. Several infants were diagnosed with endocrine disease or genetic syndromes., Conclusions: Extreme prematurity is associated with significant morbidity. Nearly all infants (92%) who developed chronic neurologic disease were diagnosed with neurologic disease during the perinatal period. Intravitreal bevacizumab, often with adjuvant photocoagulation, led to regression without detachment in 100% of eyes, with most verbal children retaining functional vision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Naravane, Belin, Rubino and Quiram.)

Background: Gangliogliomas are well-differentiated, slow-growing glioneuronal neoplasms frequently reported to harbor upregulating alterations in the mitogen-activated protein kinase pathway, particularly serine-threonine protein kinase B-RAF alterations. Fusions involving neurotrophin tyrosine receptor kinase (NTRK) genes have rarely been reported in ganglioglioma. Similarly, echinoderm microtubule-associated protein-like (EML) 4 gene fusion has been described in lung cancer, but none has been reported in ganglioglioma., Observations: This report discusses the care of a 72-year-old man presenting with medication-refractory, left-sided focal seizures who was found to have a nongadolinium-enhancing, T2-hyperintense, right frontoparietal lesion. The patient received resection, and histological analysis found a World Health Organization grade I ganglioglioma, with genetic analysis demonstrating an EML4-NTRK3 gene fusion protein., Lessons: To our knowledge, this is the first report of an NTRK3 fusion, EML4-NTRK3, in an adult ganglioglioma, which is otherwise mostly associated with BRAF alterations and activation of the mitogen-activated protein kinase signaling pathway. Further studies are needed to elucidate the function of the resultant fusion protein and determine whether it may serve as a future therapeutic target.

Introduction: The novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), etiological agent of coronavirus disease 2019 (COVID-19) was first reported in China in December 2019 and spread worldwide. As of March 6th, 2021, there have been 116,670,105 million confirmed cases globally including 2,592,085 deaths. COVID-19 cases have been reported in 219 countries and territories, creating global panic. Mozambique has witnessed the evolution of COVID-19 epidemic associated with the weakness of health system, mostly in terms of laboratory diagnosis capacity, concerns on compliance to effective public health measures including physical distancing, use of masks in crowded indoor areas, hand hygiene, isolation and quarantine of people., Methodology: The data included in this study were collected from published articles regarding COVID-19 imported cases and severity in Africa, especially in Mozambique. Additionally, official documents of COVID-19 epidemiology from Minister of Health and National Institute of Health of Mozambique from 22nd of March 2020 to 1st of August 2020 were included., Results: The SARS-CoV-2 strains imported mainly from South Africa and European countries might have been playing an important role on COVID-19 epidemic evolution in Mozambique., Conclusions: These circulating strains in the country, might be similar enough to the strains found in other countries, yet the genomic characterization is needed particularly during the phase of borders reopening through understanding the source of infections and guiding the implementation of containment and mitigation measures in the country., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 José Sumbana, Alfeu Passanduca, Salvatore Rubino.)

The development of carbapenem resistance in extraintestinal pathogenic Escherichia coli (ExPEC) has significant clinical implications, particularly in countries where second-line antimicrobials are not readily available, rendering treatments ineffective, and ExPEC infections untreatable. Thus, early detection of high-risk ExPEC lineages and raising awareness of the specific mechanisms underlying carbapenem resistance are mandatory for the selection of appropriate treatment options and the prevention of E. coli spread. This study aims to investigate the phenotypic and genotypic features of the first NDM-5 carbapenemase-producing ExPEC strain isolated from the blood of a patient admitted to the Maputo Central Hospital (MCH), in Mozambique. E. coli SSM100 isolate was identified by MALDI-TOF, it displayed high-level resistance to third generation cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides, performing antimicrobial susceptibilities testing by VITEK 2 system. E. coli SSM100 isolate was classified through whole-genome sequencing as ST405-D-O102: H6, a globally distributed lineage associated with antimicrobial resistance, carrying the bla NDM-5 gene located on an F1:A1:B49 plasmid, coharboring bla CTX-M-15, bla TEM-1, aadA2 , sul1 , and dfrA12 genes. In addition, mutations in gyrA (S83L and D87N), parC (S80I and E84V), and parE (I529L) conferring fluoroquinolone resistance were also found. Moreover, SSM100 isolate carried 88 virulence genes, of which 28 are reported to be associated with UPEC. The emergence of NDM-5 carbapenemase in a pandemic ST405-D-O102:H6 clone in Mozambique is of great concern. Locations of extended-spectrum β-lactamase determinants and NDM-5 carbapenemase gene on Inc F -plasmid can increase their spread reinforcing the need for antimicrobial surveillance and the urgent introduction of carbapenemase detection tests in diagnostic laboratories of the country.

Introduction: To analyze the virus spread among Sassari Hospital staff in the first Covid-19 wave and the impact of the Swab Team, a multidisciplinary task force entitled of nasopharyngeal swab collection and testing., Methodology: Nasopharyngeal swabs from HCWs between March 6 and May 28 2020 are evaluated., Results: 4919 SARS-CoV-2 tests were performed on 3521 operators. Nurses and doctors are the categories at highest risk. After the Swab Team institution, the average number of swabs raised from 47/day to 86/day (p = 0.007). Positive samples decreased from 18.6% to 1.7% (p < 0.0001)., Conclusions: The Swab Team is effective in increasing the cases tested and in reducing the reporting time. Procedure standardization reduces the risk for all the subjects involved (no transmission among swab team members, nor during the sample collection)., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Francesco Bussu, Davide Rizzo, Laura Saderi, Antonio Piras, Laura Maria De Luca, Giacomo De Riu, Luigi Angelo Vaira, Antonello Serra, Paola Altrudo, Domenico Delogu, Ignazio Dettori, Francesco Giuseppe Riu, Flavia Angioj, Laura Firino, Rosalba Govoni, Gabriele Ibba, Vincenzo Lai, Erica Mura, Bianca Paglietti, Claudia Piu, Anna Puggioni, Elena Rimini, Giulia Rocca, Caterina Serra, Sergio Uzzau, Salvatore Rubino, Giovanni Sotgiu.)

Severe acute respiratory syndrome coronavirus 2 infection might induce a significant and sustained lymphopenia, increasing the risk of developing opportunistic infections. Mucormycosis is a rare but severe invasive fungal infection, mainly described in immunocompromised patients. The first case of a patient diagnosed with coronavirus disease (COVID-19) who developed a pulmonary mucormycosis with extensive cavitary lesions is here reported. This case highlights how this new coronavirus might impair the immune response, exposing patients to higher risk of developing opportunistic infections and leading to worse outcomes., (© 2020. The Author(s).)

Ingestion of caustic substances, whether accidental or for the purpose of suicide, can cause severe lesions of the lips, oral cavity, pharynx, upper gastrointestinal system, and upper airways. In particular, caustic agents could be responsible for severe esophageal injuries resulting in short- and long-term complications. Because of these important clinical implications, timely diagnosis and appropriate management are crucial. In the evaluation of esophageal injuries, thoraco-abdominal computed tomography (CT) is preferable to endoscopy as it avoids the risk of esophageal perforation and allows the evaluation of esophageal injuries as well as of the surrounding tissue. In this review, we report CT findings of esophageal injuries and possible related thoracic complications caused by caustic ingestion., (© 2021. American Society of Emergency Radiology.)