Insights into the antimicrobial properties of a cationic steroid and antibiofilm performance in PDMS-based coatings to potentially treat urinary infections.

Currently, multidrug-resistant (MDR) infections are one of the most important threats, driving the search for new antimicrobial compounds. Cationic peptide antibiotics (CPAs) and ceragenins (CSAs) contain in their structures cationic groups and adopt a facially amphiphilic conformation, conferring the ability to permeate the membranes of bacteria and fungi. Keeping these features in mind, an amine steroid, DOCA-NH2, was found to be active against reference strains and MDR isolates of Gram-positive Enterococcus faecalis and Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa. The compound was active against all the tested microorganisms, having bactericidal and fungicidal activity, displaying minimal inhibitory concentrations (MICs) between 16 and 128 µg mL-1. No synergy with clinically relevant antibacterial drugs was found. However, the compound was able to completely inhibit the biofilm formation of bacteria exposed to the MIC of the compound. For E. coli and E. faecalis, inhibition of biofilm formation occurred at half the MIC. Besides, DOCA-NH2 inhibited the dimorphic transition of Candida albicans at concentrations 4 times lower than the MIC, and can reduce the microorganism virulence and biofilm formation was significantly reduced at both MIC and half the MIC. Polydimethylsiloxane-based coatings containing DOCA-NH2 (0.5, 1.0, and 1.5 wt%) were prepared and tested against the E. coli biofilm formation under hydrodynamic conditions similar to those prevailing in ureteral stents. A biofilm reduction of approximately 80% was achieved when compared to the control.

Potential use of high-resolution melting analyses for SARS-CoV-2 genomic surveillance.

The pandemic caused by COVID-19 and the emergence of new variants of SARS-CoV-2 have generated clinical and epidemiological impacts on a global scale. The use of strategies for monitoring viral circulation and identifying mutations in genomic regions involved in host interaction are important measures to mitigate viral dissemination and reduce its likely complications on population health. In this context, the objective of this work was to explore the potential of high-resolution melting (HRM) analysis combined with one-step real-time reverse transcription PCR in a closed-tube system, as a fast and convenient method of screening for SARS-CoV-2 mutations with possible implications on host-pathogen interactions. The HRM analyses allowed the distinction of the Gamma, Zeta, Alpha, Delta, and Omicron variants against the predecessors (B.1.1.28, B.1.1.33) of occurrence in Brazil. It is concluded that the molecular tool standardized here has the potential to optimize the genomic surveillance of SARS-CoV-2, and could be adapted for genomic surveillance of other pathogens, due to its ability to detect, prior to sequencing, samples suggestive of new variants, selecting them more assertively and earlier for whole genome sequencing when compared to random screening.

How Reliable Are Ultra-Short-Term HRV Measurements during Cognitively Demanding Tasks?

Ultra-short-term HRV features assess minor autonomous nervous system variations such as variations resulting from cognitive stress peaks during demanding tasks. Several studies compare ultra-short-term and short-term HRV measurements to investigate their reliability. However, existing experiments are conducted in low cognitively demanding environments. In this paper, we propose to evaluate these measurements' reliability under cognitively demanding tasks using a near real-life setting. For this purpose, we selected 31 HRV features, extracted from data collected from 21 programmers performing code comprehension, and compared them across 18 different time frames, ranging from 3 min to 10 s. Statistical significance and correlation tests were performed between the features extracted using the larger window (3 min) and the same features extracted with the other 17 time frames. We paired these analyses with Bland-Altman plots to inspect how the extraction window size affects the HRV features. The main results show 13 features that presented at least 50% correlation when using 60-second windows. The HF and mNN features achieved around 50% correlation using a 30-second window. The 30-second window was the smallest time frame considered to have reliable measurements. Furthermore, the mNN feature proved to be quite robust to the shortening of the time resolution.

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein.

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141-144, ∆211, and ∆256-258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern.

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

Identification of a novel SARS-CoV-2 P.1 sub-lineage in Brazil provides new insights about the mechanisms of emergence of variants of concern.

One of the most remarkable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) features is the significant number of mutations they acquired. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we describe a new SARS-CoV-2 P.1 sub-lineage circulating in Brazil, denoted here as Gamma-like-II, that as well as the previously described lineage Gamma-like-I shares several lineage-defining mutations with the VOC Gamma. Reconstructions of ancestor sequences support that most lineage-defining mutations of the Spike (S) protein, including those at the receptor-binding domain (RBD), accumulated at the first P.1 ancestor. In contrast, mutations outside the S protein were mostly fixed at subsequent steps. Our evolutionary analyses estimate that P.1-ancestral strains carrying RBD mutations of concern probably circulated cryptically in the Amazonas for several months before the emergence of the VOC Gamma. Unlike the VOC Gamma, the other P.1 sub-lineages displayed a much more restricted dissemination and accounted for a low fraction (<2 per cent) of SARS-CoV-2 infections in Brazil in 2021. The stepwise diversification of lineage P.1 through multiple inter-host transmissions is consistent with the hypothesis that partial immunity acquired from natural SARS-CoV-2 infections in heavily affected regions might have been a major driving force behind the natural selection of some VOCs. The lag time between the emergence of the P.1 ancestor and the expansion of the VOC Gamma and the divergent epidemic trajectories of P.1 sub-lineages support a complex interplay between the emergence of mutations of concern and viral spread in Brazil.

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B 1 1 33 Circulating in Brazil

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

Outbreak of Glomerulonephritis Caused by Streptococcus zooepidemicus SzPHV5 Type in Monte Santo de Minas, Minas Gerais, Brazil.

Streptococcus zooepidemicus is an emerging and opportunistic zoonotic pathogen which plays an important role in the development of severe and life-threatening diseases and is potentially capable of triggering large glomerulonephritis outbreaks. Between December 2012 and February 2013, 175 cases of glomerulonephritis were confirmed in the town of Monte Santo de Minas, MG, Brazil. During the outbreak, 19 isolates of S. zooepidemicus were recovered, 1 from ice cream, 2 from the oropharynx of food handlers, and 16 from patients affected by acute poststreptococcal glomerulonephritis (APSGN). All S. zooepidemicus isolates involved in the outbreak amplified the same sequence of the hypervariable region of the SzP protein (SzPHV5) and presented indistinguishable banding patterns with high similarity (>99%) to each other by the repetitive element sequence-based PCR (rep-PCR) technique. Inspection programs on the milk supply chain should be strengthened and continuously encouraged so that the health of consumers is preserved.

Persistence of Yellow fever virus outside the Amazon Basin, causing epidemics in Southeast Brazil, from 2016 to 2018.

BACKGROUND: Yellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group. METHODOLOGY/PRINCIPAL FINDINGS: Aiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017-2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage BR-YFV_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014-2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil. CONCLUSIONS: The results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.

Estudo da pressäo intra-ocular entre habitantes de Curitiba / Evaluation of intraocular pressure in Curitiba in habitants

Objetivo: Avaliar a pressäo intra-ocular (PIO) em habitantes da Cidade de Curitiba levando em consideraçäo o sexo e a idade acima de 40 anos, e comparar os valores obtidos com os descritos em outras populaçöes já estudadas. Local: Departamento de Oftalmologia do Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, PR. Método: Neste estudo, realizou-se o exame de aferiçäo da PIO atravée do tonômetro de aplanaçäo de Goldmann em um grupo de 449 indivíduos (898 olhos) composto por populaçäo carente e moradores de asilos da Cidade de Curitiba. Resultados: Encontrou-se valores crescentes da PIO com o aumento da idade; entre os sexos näo houve diferença significativa. Conclusäo: Os valores obtidos säo semelhantes aos relatados na literatura e concluímos que há uma elevaçäo da PIO de acordo com o aumento da faixa etária