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Rapid and reliable identification of microorganisms in the clinical laboratory is essential for an early and accurate diagnosis guiding timely therapy. However, conventional methods are sometimes unreliable and show controversial outcomes. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been reported as a rapid and reliable method for identification of bacteria and fungi isolated from clinical samples. Members of the genus Raoultella are increasingly recognized as clinically relevant. There are difficulties in their identification at the species level since sequencing the 16S rRNA or the rpoB genes does not show conclusive results. The aim of this study has been to compare two MALDI-TOF MS systems (Vitek MS and Bruker Biotyper) with Vitek2 and API20E systems for differentiation of Raoultella species. A collection of 97 clinical isolates of Raoultella species was identified with Vitek MS, in parallel with Vitek2 and API, and finally with Bruker Biotyper. Among the two most widely used MALDI-TOF MS platforms, results obtained with Vitek MS were slightly superior to those obtained with the Bruker Biotyper system, with sensitivities and specificities of 98.9/57.9% and 98.8/37.0%, respectively. The current commercial phenotypic identification systems are not optimized for the identification of Raoultella species. Our results indicate that MALDI-TOF-based identification is more accurate and sensitive than that provided by phenotypic methods.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome’s low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153 , OPG204 , and OPG208 , could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability. The 2023 monkeypox outbreak was caused by a subclade IIb monkeypox virus (MPXV). Here, using advanced sequencing techniques, the authors identify variations on low-complexity regions of the MPXV genome and describe their potential as evolutionary drivers.

This study sought to evaluate the effect of classical music, using Mozart’s sonata for two pianos (K. 448), on changes in dopamine (DA) levels in the striatal nucleus (SN), prefrontal cortex (PFC) and mesencephalon, and on prolactin (PRL) and corticosterone secretion in adult male Wistar rats. Rats were divided into four groups: (1) control, (2) haloperidol treatment (single dose of 2 mg/kg s.c.), (3) music (two 2-h sessions per day) and (4) haloperidol plus music. Rats were sacrificed 2 h after haloperidol injection. Music prompted a fall in plasma PRL and corticosterone levels in healthy rats ( P  < 0.05) and prevented the increase in levels triggered by haloperidol ( P  < 0.001). Moreover, exposure to music was associated with a significant increase in DA levels in all groups, with the increase being particularly marked in PFC and SN ( P  < 0.001). Haloperidol is a recognised D2 receptor antagonist, and these findings suggest that music, by contrast, enhances DA activity and turnover in the brain. The results obtained here bear out reports that music triggers a reduction in systolic pressure and an increase in mesencephalon dopamine levels in human and rats treated with ecstasy, through a calmodulin-dependent system.

The currently expanding monkeypox epidemic is caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. In contrast to monkeypox cases caused by clade I and subclade IIa MPXV, the prognosis of current cases is generally favorable, but person-to-person transmission is much more efficient. MPXV evolution is driven by selective pressure from hosts and loss of virus–host interacting genes. However, there is no satisfactory genetic explanation using single-nucleotide polymorphisms (SNPs) for the observed increased MPXV transmissibility. We hypothesized that key genomic changes may occur in the genome’s low-complexity regions (LCRs), which are highly challenging to sequence and have been dismissed as uninformative. Using a combination of highly sensitive techniques, we determined a first high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This effort revealed significant variation in short-tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of SNPs and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs) 153, 204, and 208 could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. Consequently, we posit that genomic studies focusing on phenotypic MPXV clade-/subclade-/lineage-/strain differences should change their focus to the study of LCR variability instead of SNP variability.

The recent outbreak of Monkeypox displays novel transmission features. The circulating strain is a descendant of a lineage that had been circulating in Nigeria since 2017. The prognosis of monkeypox disease (MPX) with the circulating strain is generally good but the estimated primary reproduction number (R0) among men who have sex with men (MSM) was above 1 suggesting efficient person-to-person transmission. Different mechanisms of viral entry and egress, as well as virus-coded host factors, are the main biological determinants of poxvirus transmissibility. OPXV evolution is driven by gene loss of virus-host interacting genes and selective pressure from host species using unique adaptive strategies at the gene and nucleotide level. In this context, we evaluated the effects of genomic instability in low-complexity-regions, areas that are often neglected during sequencing, during the early stage of the outbreak in Madrid, Spain. We uncovered significant variation in short-tandem repeat areas of the MPXV genome that could be associated with changes in transmissibility. Expression, translation, stability, or function of OPG153 (VACV A26L), OPG204 (VACV B16R) and OPG208 (VACV B19R) could be affected by the changes, in a manner that is consistent with proven genomic accordion strategies of OPXV evolution. Intriguingly, while the changes observed in OPG153 stand out as they are located inside a region under high selective pressure for transmission, in a gene that is clearly considered a core gene involved in attachment and egress; the changes in OPG208, a serine protease inhibitor-like protein that has been identified as an apoptosis inhibitor, host-range factor and virulence factor; and OPG204, a known inhibitor of the Type I interferon system shown to act as a decoy receptor, could also explain phenotypic changes. Further functional studies to complement this comparative genomic study are urgently needed. Competing Interest Statement The work for this study at Instituto de Salud Carlos III was partially funded by Accion Estrategica Impacto clinico y microbiologico del brote por el virus de la viruela del mono en pacientes en Espana (2022): proyecto multicentrico MONKPOX-ESP22 (CIBERINFEC). The work for this study at the GP laboratory was funded by instiutional funds of the Department of Microbiology, Icahn School of Medicine at Mount Sinai in support of Global Health Emerging Pathogen Institute activities. The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapuetics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary, Synairgen and Pfizer, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. Footnotes * Added Disclaimer of United States Army personnel. Corrected an error regarding the codon usage in one of the promoters of OPG204.