The ROK kinase N-acetylglucosamine kinase uses a sequential random enzyme mechanism with successive conformational changes upon each substrate binding.

N-acetyl-d-glucosamine (GlcNAc) is a major component of bacterial cell walls. Many organisms recycle GlcNAc from the cell wall or metabolize environmental GlcNAc. The first step in GlcNAc metabolism is phosphorylation to GlcNAc-6-phosphate. In bacteria, the ROK family kinase N-acetylglucosamine kinase (NagK) performs this activity. Although ROK kinases have been studied extensively, no ternary complex showing the two substrates has yet been observed. Here, we solved the structure of NagK from the human pathogen Plesiomonas shigelloides in complex with GlcNAc and the ATP analog AMP-PNP. Surprisingly, PsNagK showed distinct conformational changes associated with the binding of each substrate. Consistent with this, the enzyme showed a sequential random enzyme mechanism. This indicates that the enzyme acts as a coordinated unit responding to each interaction. Our molecular dynamics modeling of catalytic ion binding confirmed the location of the essential catalytic metal. Additionally, site-directed mutagenesis confirmed the catalytic base and that the metal-coordinating residue is essential. Together, this study provides the most comprehensive insight into the activity of a ROK kinase.

Ruthenium Metallotherapeutics: Novel Approaches to Combatting Parasitic Infections.

Human parasitic infections cause a combined global mortality rate of over one million people per annum and represent some of the most challenging diseases for medical intervention. Current chemotherapeutic strategies often require prolonged treatment, coupled with subsequent drug-induced cytotoxic morbidity to the host, while resistance generation is also a major concern. Metals have been used extensively throughout the history of medicine, with more recent applications as anticancer and antimicrobial agents. Ruthenium metallotherapeutic antiparasitic agents are highly effective at targeting a range of key parasites, including the causative agents of malaria, trypanosomiasis, leishmaniasis, amoebiasis, toxoplasmosis and other orphan diseases, while demonstrating lower cytotoxicity profiles than current treatment strategies. Generally, such compounds also demonstrate activity against multiple cellular target sites within parasites, including inhibition of enzyme function, cell membrane perturbation, and alterations to metabolic pathways, therefore reducing the opportunity for resistance generation. This review provides a comprehensive and subjective analysis of the rapidly developing area of ruthenium metal- based antiparasitic chemotherapeutics, in the context of rational drug design and potential clinical approaches to combatting human parasitic infections.

Natural Antimicrobial Nano Composite Fibres Manufactured from a Combination of Alginate and Oregano Essential Oil.

Alginate is a linear biodegradable polysaccharide polymer, which is bio-renewable and widely used for various biomedical applications. For the next generation of medical textiles, alginate nanofibres are desirable for their use in wound dressings that are biocompatible, sustainable, and abundantly available. This study has developed a unique manufacturing process for producing alginate nanofibres with exceptional antimicrobial properties of oregano essential oil (OEO) as a natural antimicrobial agent. OEO with varying degrees of concentration was incorporated in an aqueous alginate solution. Appropriate materials and electrospinning process parameter selection allowed us to manufacture alginate fibres with a range of diameters between 38 and 105 nm. A unique crosslinking process for alginate nanofibres using extended water soaking was developed. Mechanical characterisation using micro-mechanical testing of nonwoven electrospun alginate/oregano composite nanofibres revealed that it was durable. An extensive antimicrobial study was carried out on alginate/oregano composite nanofibres using a range of Gram-positive (methicillin-resistant Staphylococcus aureus (MRSA) and Listeria monocytogenes) and Gram-negative bacteria (Klebsiella pneumoniae and Salmonella enterica), which are common wound and food pathogens. The results indicated that increasing the concentration of OEO from 2 to 3 wt % showed improved antimicrobial activity against all pathogens, and activity was significantly improved against MRSA compared to a non-alginate-based control disk containing OEO. Therefore, our research suggests that all-natural alginate/oregano nanofibre composite textiles offer a new generation of medical textiles for advanced wound dressing technology as well as for food packaging applications.

Is delirium being detected in emergency?

OBJECTIVE: To report on the use of Delirium Care Pathways to screen for and recognise delirium by Aged Care Services in Emergency Teams (ASETs) at five metropolitan hospitals in New South Wales, Australia. Knowledge of delirium and the use of Delirium Care Pathways are vital to ensure that older people presenting with delirium receive best practice care. METHODS: An audit of 205 randomly selected medical records of clients over 65 years presenting to an ASET was conducted. RESULTS: Delirium was recorded in the medical records notes of four clients (2%). However, the auditors identified another 27 clients with symptoms of delirium. CONCLUSIONS: Delirium is still frequently undiagnosed and misdiagnosed in older people presenting to emergency departments. This indicates a need for further education and professional development for and by health-care practitioners. Only with greater awareness of delirium will the care and health outcomes of older adults presenting with delirium in acute care settings improve.

Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program.

BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students' learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.

Using business plan development as a capstone project for MPH programs in Canada: validation through the student perspective.

Master of Public Health (MPH) programs have been developed across Canada as a response to the need for adequately trained individuals to work in the public health sector. Educational institutions that deliver MPH programs have a responsibility to ensure that graduates of their program have the essential knowledge, skills and attitudes to begin a successful career in public health. The Public Health Agency of Canada has created the core competencies for public health to guide the development, delivery and evaluation of MPH programs. In Canada, a capstone project is the recommended method of evaluating the MPH graduate's ability to demonstrate proficiency in the public health core competencies. A business plan that develops the framework for a public health program is an ideal capstone project currently used in practice within the University of Guelph MPH program. This group assignment incorporates all 36 of the public health core competencies while providing students with a real-world public health experience, and should be considered for inclusion within MPH programs across Canada. Business planning provides students the opportunity to engage in practice-based learning, applying theoretical knowledge to practice. Further, the ability to develop realistic but financially feasible public health problems is an invaluable skill for MPH graduates. As the development of programs becomes more restricted and the continuation of other programs are under constant threat, the ability to develop a sound business plan is a required skill for individuals entering the public health sector, and will ensure students are able to maximize outcomes given tight fiscal budgets and limited resources.