Preparation and Evaluation of Potent Pentafluorosulfanyl-Substituted Anti-Tuberculosis Compounds.

The global fight to stop tuberculosis (TB) remains a great challenge, particularly with the increase in drug-resistant strains and a lack of funding to support the development of new treatments. To bolster a precarious drug pipeline, we prepared a focused panel of eight pentafluorosulfanyl (SF5 ) compounds which were screened for their activity against Mycobacterium tuberculosis (Mtb) H37Rv in three different assay conditions and media. All eight compounds had sub-micromolar potency, and four displayed MICs <100 nm. Seven compounds were evaluated against non-replicating and mono-drug-resistant Mtb, and for their ability to inhibit Mtb within the macrophage. The greatest potency was observed against intracellular Mtb (MIC <10 nm for three compounds), which is often the most challenging to target. In general, the SF5 -bearing compounds were very similar to their CF3 counterparts, with the major differences observed being their in vitro ADME properties. Two SF5 -bearing compounds were found to have greater protein binding than their corresponding CF3 counterparts, but were also less metabolized in human microsomes, resulting in longer half-lives.

Supporting intensive interventions for students with autism spectrum disorder: performance feedback and discrete trial teaching.

This study evaluated the impact of performance feedback on nine public educators' level of procedural integrity to Discrete Trial Teaching (DTT) procedures for students with Autism Spectrum Disorder (ASD). Procedural integrity was observed during four phases: no feedback, general feedback, performance feedback, and maintenance, in a multiple baseline across participants design. Results indicate that for most educators, performance feedback is necessary to improve and maintain integrity at or above 80%. Most participants' performance during no feedback and general feedback was characterized by high rates of variability. One participant required in vivo feedback to achieve and maintain acceptable levels of integrity. Procedural modifications necessary to adapt this procedure to the applied environment of school are discussed. Findings suggest that highly structured evidence-based interventions for students with ASD require consultation support to be implemented with integrity in schools, and the duration and intensity of support needed may be higher than for other interventions. These promising findings emphasize the important role of school psychologists and other support personnel in ensuring that services are delivered as intended.