Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase.

Substitutions at residue Y181 in HIV-1 reverse transcriptase (RT), in particular, Y181C, Y181I, and Y181V, are associated with nonnucleoside RT inhibitor (NNRTI) cross-resistance. In this study, we used kinetic and thermodynamic approaches, in addition to molecular modeling, to gain insight into the mechanisms by which these substitutions confer resistance to nevirapine (NVP), efavirenz (EFV), and rilpivirine (RPV). Using pre-steady-state kinetics, we found that the dissociation constant ( ) values for inhibitor binding to the Y181C and Y181I RT-template/primer (T/P) complexes were significantly reduced.

Small-Molecule Inhibitor of FosA Expands Fosfomycin Activity to Multidrug-Resistant Gram-Negative Pathogens.

The spread of multidrug or extensively drug-resistant Gram-negative bacteria is a serious public health issue. There are too few new antibiotics in development to combat the threat of multidrug-resistant infections, and consequently the rate of increasing antibiotic resistance is outpacing the drug development process. This fundamentally threatens our ability to treat common infectious diseases.

Characteristics of evoked potential multiple EEG recordings in patients with chronic pain by means of parallel factor analysis.

This paper presents an alternative method, called as parallel factor analysis (PARAFAC) with a continuous wavelet transform, to analyze of brain activity in patients with chronic pain in the time-frequency-channel domain and quantifies differences between chronic pain patients and controls in these domains. The event related multiple EEG recordings of the chronic pain patients and non-pain controls with somatosensory stimuli (pain, random pain, touch, random touch) are analyzed. Multiple linear regression (MLR) is applied to describe the effects of aging on the frequency response differences between patients and controls.

Practical use of the raw electroencephalogram waveform during general anesthesia: the art and science.

Quantitative electroencephalogram (qEEG) monitors are often used to estimate depth of anesthesia and intraoperative recall during general anesthesia. As with any monitor, the processed numerical output is often misleading and has to be interpreted within a clinical context. For the safe clinical use of these monitors, a clear mental picture of the expected raw electroencephalogram (EEG) patterns, as well as a knowledge of the common EEG artifacts, is absolutely necessary.

The howling cortex: seizures and general anesthetic drugs.

The true incidence of seizures caused by general anesthetic drugs is unknown. Abnormal movements are common during induction of anesthesia, but they may not be indicative of true seizures. Conversely, epileptiform electrocortical activity is commonly induced by enflurane, etomidate, sevoflurane and, to a lesser extent, propofol, but it rarely progresses to generalized tonic-clonic seizures.

Pharmacokinetic-pharmacodynamic modeling the hypnotic effect of sevoflurane using the spectral entropy of the electroencephalogram.

Spectral entropy is a new electroencephalogram (EEG)-derived parameter that may be used to model the pharmacokinetic-pharmacodynamic (PKPD) effects of general anesthetics. In the present study we sought to derive a PKPD model of the relationship between sevoflurane concentration and spectral entropy of the EEG. We collected spectral entropy data during increasing and decreasing sevoflurane anesthesia from 20 patients.