Expansion of healthcare-associated hypervirulent KPC-2-producing ST11/KL64 beyond hospital settings.

The spread of carbapenemase-producing beyond hospital settings is a global critical issue within a public health and One Health perspective. Another worrisome concern is the convergence of virulence and resistance in healthcare-associated lineages of leading to unfavorable clinical outcomes. During a surveillance study of WHO critical priority pathogens circulating in an impacted urban river in São Paulo, Brazil, we isolate two hypermucoviscous and multidrug-resistant strains (PINH-4250 and PINH-4900) from two different locations near to medical centers.

Multi-channel and multi-harmonic analysis of Auditory Steady-State Response detection.

The Auditory Steady-State Response (ASSR) is a type of auditory evoked potential (AEP) generated in the auditory system that can be automatically detected by means of objective response detectors (ORDs). ASSRs are usually registered on the scalp using electroencephalography (EEG). ORD are univariate techniques, i.

Dealing with correlations in the multichannel EEG using bipolar derivations and Monte Carlo simulations: application to the detection of auditory steady-state responses.

The multichannel objective response detection (MORD) techniques are statistical methods, which use information from more than one electroencephalography (EEG) channel, to infer the presence of evoked potential. However, the correlation level between the channels can lead to a decrease in MORD performance, such as an increase in the false positive (FP) rate and/or a decrease in the detection rate (DR). The present study aims to propose a method to deal with the correlations in the multichannel EEG.

Improved Protocol for the Selection of Structures from Molecular Dynamics of Organic Systems in Solution: The Value of Investigating Different Wavelet Families.

Wavelets are mathematical tools used to decompose and represent another function described in the time domain, allowing the study of each component of the original function with a scale-compatible resolution. Thus, these transforms have been used to select conformations from molecular dynamics (MD) trajectories in systems of fundamental and technological interest. Recently, our research group has used wavelets to develop and validate a method, meant to select structures from MD trajectories, which we named OWSCA (optimal wavelet signal compression algorithm).

Automatic audiometry using auditory steady-state response and sequential test strategy applied to volunteers with normal hearing.

Purpose: In the present study, a new procedure to perform automatic audiometry using multifrequency Auditory Steady-State Response (ASSR) is proposed.

Methods: The automatic audiometry procedure consists of detecting the presence of multifrequency ASSR in real-time using the sequential test strategy and by adjusting the stimulus intensity independently. The ASSR audiometric thresholds of 18 adult volunteers with normal hearing were determined by automatically (four simultaneous frequencies per ear) at modulation frequencies in the 80 Hz range.

Docking and molecular dynamics studies of potential new leads against DBL3x derived from chondroitin sulfate A (CSA): a new approach for the treatment of malaria.

In this work the DBL3x domain of the erythrocyte membrane protein from (EMP1), was revisited as a potential molecular target for the development of new drugs against malaria. This protein interacts with chondroitin sulfate A (CSA), a glycosaminoglycan present in the substance fundamental for connective tissues of vertebrates and is implicated in malaria complications in pregnant women. We performed molecular docking and molecular dynamic studies of DBL3x complexed with CSA and five analogues, where the sulfate group was replaced by phosphate, in order to evaluate if the better electrostatic interactions provided by phosphate groups could afford better binders capable of preventing the binding of CSA to DBL3x.

Multichannel search strategy for improving the detection of auditory steady-state response.

Auditory steady-state response (ASSR) is useful for hearing threshold estimation. The ASSR is usually detected with objective response detectors (ORD). The performance of these detectors depends on the signal-to-noise ratio (SNR) as well as the signal length.

Molecular Modeling Study of Uncharged Oximes Compared to HI-6 and 2-PAM Inside Human AChE Sarin and VX Conjugates.

The deleterious effects of nerve agents over the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) turned these compounds into the most dangerous chemical weapons known. Among the antidotes in use today against these agents, oximes in combination with other drugs are the only treatment with any action. HI-6 and 2-PAM are cationic oximes proved to be effective for the reactivation of AChE inhibited by the nerve agents VX and sarin (GB).

Faster automatic ASSR detection using sequential tests.

Objective Response Detection (ORD) can be used for auditory steady-state response (ASSR) detection. In conventional ORD methods, the statistical tests are applied at the end of data collection ('single-shot tests'). In sequential ORD methods, statistical tests are applied repeatedly, while data is being collected.

Automated detection of auditory response: applying sequential detection strategies with constant significance level to magnitude-squared coherence.

Abstracts The detection of the auditory steady-state responses is usually performed by an appropriate objective response detector applied to stimulus-related epochs of the raw electroencephalogram (EEG). In order to improve the detection time, sequential detection strategies are usually used. These multiple tests strategies increase the probability of mistakenly detecting a response.

Computational studies of mucin 2 and its interactions with thiolated chitosans: a new insight for mucus adhesion and drug retention.

Chitosans have attracted the interest of the medicinal chemists as mucous adhesive excipients capable of increasing the residence period of drugs inside mucous membranes. Their interactions with the oligomeric mucus gel-forming glycoprotein mucin 2 throughout the intestine determine the level of mucus adhesion, which can be potentiated by the insertion of thiolated substituents on its structure. In this work, we studied the interactions between the mucin 2 and thiolated chitosans, ranking them based on the free energy of receptor-ligand interaction.

The role of the oximes HI-6 and HS-6 inside human acetylcholinesterase inhibited with nerve agents: a computational study.

The oximes 4-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HI-6) and 3-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HS-6) are isomers differing from each other only by the position of the carbamoyl group on the pyridine ring. However, this slight difference was verified to be responsible for big differences in the percentual of reactivation of acetylcholinesterase (AChE) inhibited by the nerve agents tabun, sarin, cyclosarin, and VX. In order to try to find out the reason for this, a computational study involving molecular docking, molecular dynamics, and binding energies calculations, was performed on the binding modes of HI-6 and HS-6 on human AChE (HssAChE) inhibited by those nerve agents.

Computational studies of acetylcholinesterase complexed with fullerene derivatives: a new insight for Alzheimer disease treatment.

Here, we propose five fullerene (C60) derivatives as new drugs against Alzheimer's disease (AD). These compounds were designed to act as new human acetylcholinesterase (HssAChE) inhibitors by blocking its fasciculin II (FASII) binding site. Docking and molecular dynamic results show that our proposals bind to the HssAChE tunnel entrance, forming stable complex, and further binding free energy calculations suggest that three of the derivatives proposed here could be potent HssAChE inhibitors.

Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox.

Recently we constructed a homology model of the enzyme thymidylate kinase from Variola virus (VarTMPK) and proposed it as a new target to the drug design against smallpox. In the present work, we used the antivirals cidofovir and acyclovir as reference compounds to choose eleven compounds as leads to the drug design of inhibitors for VarTMPK. Docking and molecular dynamics (MD) studies of the interactions of these compounds inside VarTMPK and human TMPK (HssTMPK) suggest that they compete for the binding region of the substrate and were used to propose the structures of ten new inhibitors for VarTMPK.

Molecular modeling toward selective inhibitors of dihydrofolate reductase from the biological warfare agent Bacillus anthracis.

In the present work, we applied docking and molecular dynamics techniques to study 11 compounds inside the enzymes dihydrofolate reductase (DHFR) from the biological warfare agent Bacillus anthracis (BaDHFR) and Homo sapiens sapiens (HssDHFR). Six of these compounds were selected for a study with the mutant BaF96IDHFR. Our results corroborated with experimental data and allowed the proposition of a new molecule with potential activity and better selectivity for BaDHFR.