Improving the Brightness of Pyronin Fluorophore Systems through Quantum-Mechanical Predictions.

The pyronin class of fluorophores serves a critical role in numerous imaging applications, particularly involving preferential staining of RNA through base pair intercalation. Despite this important role in molecular staining applications, the same set of century-old pyronins (i.e., pyronin Y (PY) and pyronin B (PB)), which possess relatively low fluorophore brightness, are still predominantly being used due to the lack of methodology for generating enhanced variants. Here, we use TD-DFT calculations of interconversion energies between structures on the S1 surface as a preliminary means to evaluate fluorophore brightness for a proposed set of pyronins containing variable substitution patterns at the 2, 3, 6, and 7 positions. Using a nucleophilic aromatic substitution/hydride addition approach, we synthesized the same set of pyronins and demonstrate that quantum-mechanical computations are useful for predicting fluorophore performance. We produced the brightest series of pyronin fluorophores described to date, which possess considerable gains over PY and PB.

Safety and Efficacy of Apixaban Use in Peritoneal Dialysis: A Review of the Literature.

Objective: To review the safety and efficacy of apixaban for the treatment of nonvalvular atrial fibrillation or venous thromboembolism in patients receiving peritoneal dialysis (PD). Data Sources: A PubMed and MEDLINE search was conducted through December 2020 using the following keywords and Medical Subject Headings (MeSH) terms alone or in various combinations: apixaban, peritoneal dialysis, continuous ambulatory peritoneal dialysis, end-stage renal disease, and hemodialysis. Study Selection and Data Extraction: English-language studies evaluating clinical outcomes pertaining to the use of apixaban in end stage renal disease (ESRD), which included patients receiving peritoneal dialysis were eligible for inclusion. Data Synthesis: Four studies were identified that met inclusion for this review, all retrospective in nature. These studies compared the safety and efficacy of apixaban with standard therapy in ESRD included patients on dialysis, with a very limited number of subjects receiving PD. In these studies, apixaban was shown to be potentially safer and more effective than warfarin. Outcomes did not differentiate between patients receiving PD or not. Conclusions: Use of apixaban in patients receiving PD may be safe and effective based on data from limited patients. Pharmacokinetics and pharmacodynamics of apixaban in the PD setting is an important question that clinicians should consider with use of this medication in the ESRD population. More studies focusing on the PD population are needed to better assess the use of apixaban in this understudied population.

AAC Technologies with Visual Scene Displays and "Just in Time" Programming and Symbolic Communication Turns Expressed by Students with Severe Disability.

BACKGROUND: The current study investigated the impact of an intervention that included aided augmentative and alternative communication (AAC) technologies on the frequency of symbolic communication turns of school-age children, adolescents, and young adults with severe disability. METHOD: Nine students ages 8-20 were engaged in interactive activities using an aided AAC system with visual scene displays (VSDs; concepts embedded within a photograph of a naturally occurring event), and "just-in-time" (JIT) programming (the capability to add new contexts "on the fly"). Effectiveness was evaluated using a single subject multiple probe across participants design. RESULTS: All participants demonstrated increases in symbolic communication turns upon introduction of the AAC technologies with VSDs using JIT technology. CONCLUSIONS: AAC with VSDs and JIT programming may be effective in increasing symbolic communication for students with severe developmental disability. The fast and easy creation of VSDs and hotspots to provide communication may be a valuable tool for interventionists.

Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing.

BACKGROUND: Regulated autoprocessing of HIV Gag-Pol precursor is required for the production of mature and fully active protease. We previously reported that H69E mutation in a pseudo wild type protease sequence significantly (>20-fold) impedes protease maturation in an in vitro autoprocessing assay and in transfected mammalian cells. RESULTS: Interestingly, H69E mutation in the context of a laboratory adapted NL4-3 protease showed only moderate inhibition (approximately 4-fold) on protease maturation. There are six point mutations (Q7K, L33I, N37S, L63I, C67A, and C95A) between the NL4-3 and the pseudo wild type proteases suggesting that the H69E effect is influenced by other residues. Mutagenesis analyses identified C95 as the primary determinant that dampened the inhibitory effect of H69E. L63 and C67 also demonstrated rescue effect to a less extent. However, the rescue was completely abolished when H69 was replaced by aspartic acid in the NL4-3 backbone. Charge substitutions of surface residues (E21, D30, E34, E35, and F99) to neutral or positively charged amino acids failed to restore protease autoprocessing in the context of H69E mutation. CONCLUSIONS: Taken together, we suggest that residue 69 along with other amino acids such as C95 plus L63 and C67 to a less extent modulate precursor structures for the regulation of protease autoprocessing in the infected cell.