Enacting a diversity, equity, inclusion, and justice emphasis in graduate and professional leadership education.

This article explores leadership education, leadership scholarship, and leadership practices with a focus on the continued growth in thought, paradigm development, research and practices that address societal problems in relation to human existence. We respond to the question "how can the integration of counter narratives into leadership education - all while integrating diverse perspectives into our leadership education conversation so the complexity we now understand to be true can be revealed?" The exploration creates opportunities to deepen the diversity, equity, and inclusion discourse incorporated into graduate leadership education programs.

Envisioning the future of graduate and professional leadership education: Perspectives from the field.

The future of graduate and professional leadership education holds both challenges and promise. By sharing results from a focus group study about the field of leadership education, this article uplifts the voices of leadership educators and students who shared their hopes and concerns for the field. Their advice serves as a resource to those considering ways they might best serve students and organizations through the development and enhancement of programs.

A call for the leadership education field.

The collective message of this series of articles was formed by the thoughts of seasoned leadership educators. Their truth and investment in leadership education are clear. In this closing article, we share our thoughts on their many perspectives, ideas, and challenges. This article summarizes and synthesizes these articles with the metaphor of the bamboo field that strongly relates to the field of leadership education today.

Systematic Screening, Rational Development, and Initial Optimization of Efficacious RNA Silencing Agents for Human Rod Opsin Therapeutics.

PURPOSE: To systematically evaluate human rod opsin (hRHO) mRNA for potential target sites sensitive to posttranscriptional gene silencing (PTGS) by hammerhead ribozyme (hhRz) or RNA interference (RNAi) in human cells. To develop a comprehensive strategy to identify and optimize lead candidate agents for PTGS gene therapeutics. METHODS: In multidisciplinary RNA drug discovery, computational mRNA accessibility and in vitro experimental methods using reverse transcription-polymerase chain reaction (RT-PCR) were used to map accessibility in full-length hRHO transcripts. HhRzs targeted predicted accessible and inaccessible sites and were screened for cellular knockdown using a bicistronic reporter construct. Lead hhRz and RNAi PTGS agents were rationally optimized for target knockdown in human cells. RESULTS: Systematic screening of hRHO mRNA targeting agents resulted in lead candidate identification of a novel hhRz embedded in an RNA scaffold. Rational optimization strategies identified a minimal 725 hhRz as the most active agent. Recently identified tertiary accessory elements did not enhance activity. A 725-short-hairpin RNA (shRNA) agent exerts log-order knockdown. Silent modulation of the 725-hhRz target site in hRHO mRNA resulted in resistance to knockdown. CONCLUSIONS: Combining rational RNA drug design with cell-based screening allowed rapid identification of lead agents targeting hRHO. Optimization strategies identified the agent with highest intracellular activity. These agents have therapeutic potential in a mutation-independent strategy for adRP, or other degenerations where hRHO is a target. This approach can be broadly applied to any validated target mRNA, regardless of the disease. TRANSLATIONAL RELEVANCE: This work establishes a platform approach to develop RNA biologicals for the treatment of human disease.

Crystal structure of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase from the ESKAPE pathogen Acinetobacter baumannii.

The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase catalyzes the sixth step of the seven-step shikimate pathway. Chorismate, the product of the pathway, is a precursor for the biosynthesis of aromatic amino acids, siderophores and metabolites such as folate, ubiquinone and vitamin K. The shikimate pathway is present in bacteria, fungi, algae, plants and apicomplexan parasites, but is absent in humans. The EPSP synthase enzyme produces 5-enolpyruvylshikimate 3-phosphate and phosphate from phosphoenolpyruvate and shikimate 3-phosphate via a transferase reaction, and is the target of the herbicide glyphosate. The Acinetobacter baumannii gene encoding EPSP synthase, aroA, has previously been demonstrated to be essential during host infection for the growth and survival of this clinically important drug-resistant ESKAPE pathogen. Prephenate dehydrogenase is also encoded by the bifunctional A. baumannii aroA gene, but its activity is dependent upon EPSP synthase since it operates downstream of the shikimate pathway. As part of an effort to evaluate new antimicrobial targets, recombinant A. baumannii EPSP (AbEPSP) synthase, comprising residues Ala301-Gln756 of the aroA gene product, was overexpressed in Escherichia coli, purified and crystallized. The crystal structure, determined to 2.37 Å resolution, is described in the context of a potential antimicrobial target and in comparison to EPSP synthases that are resistant or sensitive to the herbicide glyphosate.

Aseptic technique for accessing central venous catheters: applying a standardised tool to audit 'scrub the hub' practices.

BACKGROUND: To reduce the risk of infections associated with indwelling central venous catheters (CVCs), practices for hub disinfection have been widely promoted. The objective of this study was to design and implement a standardised tool to monitor compliance with 'scrub the hub' practices at an Australian centre. METHODS: Review of existing literature and recommendations regarding scrub the hub practices was performed to identify nine key components that could be audited by direct observation of staff in clinical areas. The tool was reviewed by stakeholders in infection prevention, infectious diseases and senior nursing roles prior to pilot evaluation. RESULTS: Twenty attempts to access a CVC were audited. In all instances, scrub the hub practices were commenced. However, a 15-second scrub was performed in only 60% of cases, and the hub was permitted to dry in only 65% of instances. With respect to maintaining an aseptic field, the overall compliance was 40%, and compliance was lowest for maintenance of a non-touch technique for key parts and sites, and hand hygiene practices following CVC access. CONCLUSIONS: A standardised clinical audit tool for monitoring aseptic access of CVCs enabled identification of practices amendable to targeted intervention and education, such as duration of hub disinfection. This tool would be readily utilised to facilitate quality improvement initiatives in a range of healthcare contexts, including high-risk inpatient and ambulatory care settings.

Structure of shikimate kinase, an in vivo essential metabolic enzyme in the nosocomial pathogen Acinetobacter baumannii, in complex with shikimate.

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that is an important cause of healthcare-associated infections exhibiting high mortality rates. Clinical isolates of multidrug-resistant (MDR) and extremely drug-resistant (XDR) A. baumannii strains are increasingly being observed. Compounding this concern is the dearth of new antibacterial agents in late-stage development that are effective against MDR and XDR A. baumannii. As part of an effort to address these concerns, two genes (aroA and aroC) of the shikimate pathway have previously been determined to be essential for the growth and survival of A. baumannii during host infection (i.e. to be essential in vivo). This study expands upon these results by demonstrating that the A. baumannii aroK gene, encoding shikimate kinase (SK), is also essential in vivo in a rat soft-tissue infection model. The crystal structure of A. baumannii SK in complex with the substrate shikimate and a sulfate ion that mimics the binding interactions expected for the ß-phosphate of ATP was then determined to 1.91 Å resolution and the enzyme kinetics were characterized. The flexible shikimate-binding domain and LID region are compared with the analogous regions in other SK crystal structures. The impact of structural differences and sequence divergence between SKs from pathogenic bacteria that may influence antibiotic-development efforts is discussed.