ABSTRACT
Introduction: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population. Methods: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE). Results: We screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2 ± 8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention. Conclusions: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe. Trial registration: ClinicalTrials.gov Identifier: NCT03061097.
ABSTRACT
Introduction: The early part of this century saw an unprecedented growth in number and size of Australian medical schools. There was some partnering of the new schools with existing programs. Griffith, Deakin and Curtin Universities leased an established curriculum from Flinders University. Nature and rationale for curriculum leasing: The new schools had short startup times and leasing a curriculum enabled them to appoint key staff, develop facilities and meet accreditation requirements in a timely way. However, the lease arrangements were costly and the curriculum was largely determined before the Dean and key staff appointments. Outcomes of leasing: There was differential adoption of the leased curriculum. The first two years of the courses at Flinders were transferred with little change. The final two years of predominantly clinical studies were developed differently. This is explained through Michael Fullan's work on context in educational change. The context of the clinical years of the courses involved negotiations with local health services and other schools using those health services. The advantage of the leasing arrangements was that the new schools could proceed through early development and accreditation, while having time and opportunity to negotiate a clinical curriculum that engaged local health services and fulfilled the new schools' missions.
Subject(s)
Curriculum/standards , Education, Medical, Undergraduate/organization & administration , Schools, Medical/organization & administration , Accreditation , Australia , Education, Medical, Undergraduate/economics , Education, Medical, Undergraduate/standards , Humans , Schools, Medical/economics , Schools, Medical/standardsABSTRACT
Neocarzinostatin (NCS) a potent DNA-damaging, anti-tumor toxin extracted from Streptomyces carzinostaticus that recognizes double-stranded DNA bulge and induces DNA damage. 2 Fluoro (2F) Modified EpCAM RNA aptamer is a 23-mer that targets EpCAM protein, expressed on the surface of epithelial tumor cells. Understanding the interaction between NCS and the ligand is important for carrying out the targeted tumor therapy. In this study, we have investigated the biophysical interactions between NCS and 2-fluro Modified EpCAM RNA aptamer using Circular Dichroism (CD) and Infra-Red (IR) spectroscopy. The aromatic amino acid residues spanning the ß sheets of NCS are found to participate in intermolecular interactions with 2 F Modified EpCAM RNA aptamer. In-silico modeling and simulation studies corroborate with CD spectra data. Furthermore, it reinforces the involvement of C and D1 strand of NCS in intermolecular interactions with EpCAM RNA aptamer. This the first report on interactions involved in the stabilization of NCS-EpCAM aptamer complex and will aid in the development of therapeutic modalities towards targeted cancer therapy.
Subject(s)
Antigens, Neoplasm/chemistry , Antigens, Neoplasm/ultrastructure , Aptamers, Nucleotide/chemistry , Cell Adhesion Molecules/chemistry , Cell Adhesion Molecules/ultrastructure , Models, Chemical , Molecular Docking Simulation , Zinostatin/chemistry , Binding Sites , Cytotoxins , Epithelial Cell Adhesion Molecule , Molecular Conformation , Protein Binding , Protein Interaction Mapping/methodsABSTRACT
The synthesis and cellular uptake of fluorescently labelled PNA-peptide conjugates is described; Dde/Mmt protected PNA monomers, fully orthogonal to Fmoc chemistry, were used to develop a flexible strategy to give Peptide Nucleic Acids conjugated to tri- and hepta-arginine and the short basic Tat(48-57) peptide as examples of cellular penetrating peptides, thereby allowing efficient cellular delivery of PNA into cells.
