Use of Crystallography and Molecular Modeling for the Inhibition of the Botulinum Neurotoxin A Protease

Botulinum neurotoxins (BoNTs) are extremely toxic and have been deemed a Tier 1 potential bioterrorism agent. The most potent and persistent of the BoNTs is the “A” serotype, with strategies to counter its etiology focused on designing small-molecule inhibitors of its light chain (LC), a zinc-dependent metalloprotease. The successful structure-based drug design of inhibitors has been confounded as the LC is highly flexible with significant morphological changes occurring upon inhibitor binding. To achieve greater success, previous and new cocrystal structures were evaluated from the standpoint of inhibitor enantioselectivity and their effect on active-site morphology. Based upon these structural insights, we designed inhibitors that were predicted to take advantage of π–π stacking interactions present in a cryptic hydrophobic subpocket. Structure–activity relationships were defined, and X-ray crystal structures and docking models were examined to rationalize the observed potency differences between inhibitors.     

Neurological involvement associated with COVID-19 disease: a study on psychosocial factors

Neurological Sciences - Several people affected by COVID-19 experienced neurological manifestations, altered sleep quality, mood disorders, and disability following hospitalization for a long time....     

Are Role and Gender Related to Sexual Function and Satisfaction in Men and Women Practicing BDSM?

Background

Published studies show good psychological health of people involved in bondage-discipline, dominance-submission, and sadism-masochism (BDSM) activities; nevertheless, there are few studies on characteristics related to gender, role in the BDSM scene, sexual functioning, and satisfaction among BDSM practitioners.

Expanding pharmacy roles and the interprofessional experience in primary healthcare: A qualitative study

The pharmacist role is undergoing significant changes which are reshaping the way primary healthcare is delivered throughout England. Due to increased physician workload and focus on primary healthcare, the pharmacist role has expanded to provide enhanced patient services, integrating into general practice (GP) settings and working more closely as a member of the healthcare team. However, the experiences of pharmacists and team members are yet to be explored. The proposed study aims to explore the experiences, thoughts, and perceptions of a purposive sample of pharmacists, physicians, and nurses working in 10 GP clinics throughout the southeast of England. Interprofessional relationships, power dynamics, changing professional roles, and barriers and facilitators to the integration of the pharmacist role will be explored. An exploratory multiple case study design will be used to investigate interprofessional experiences within and between clinics. In-depth interviews will be completed with each participant. A thematic analysis will identify themes and patterns from the interview data. Results are expected to produce recommendations to help facilitate the integration of pharmacists in their new role and will have implications for interprofessional collaboration and interprofessional education which are important for delivering safe and effective care.