Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.

A BCG kill switch strain protects against Mycobacterium tuberculosis in mice and non-human primates with improved safety and immunogenicity.

Improved vaccination strategies for tuberculosis are needed. Intravenous (i.v.

Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.

Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim.

Home dialysis: there's no place like home.

Purpose Of Review: The rapid rise in incidence and prevalence of end-stage kidney disease (ESKD) over the past 50 years was matched by a drop-off in use of home dialysis and a proliferation of in-center hemodialysis across the United States. There is renewed interest in improving access to home dialysis modalities for patients with ESKD. The aim of this review is to update kidney care providers with clinical outcome data and new guidelines that promote patient-centered choices, and to address barriers to home dialysis uptake and continued use.

The effect of binaural pulse modulation (B.P.M) on brain state in depression and anxiety: a case series.

Objective: In this pilot study a binaural pulse modulator was tested to see if it leads to a change in self-reported measures of distress. This binaural pulse modulator produces two frequencies that combine to create a binaural pulse to stimulate the nervous system through a differential auditory tone presentation and the response of the user can be adjusted to the appropriate target tone for effective treatment use. Each individual calibrated the binaural pulse to increase the level of emotion experienced while imagining an experience with a similar emotional valence or while engaged in a cognitive function while also listening to the sound.