What is stopping us? An implementation science study of kangaroo care in British Columbia's neonatal intensive care units.

BACKGROUND: The goal of the Neonatal Intensive Care Unit (NICU) is to provide optimal care for preterm and sick infants while supporting their growth and development. The NICU environment can be stressful for preterm infants and often cannot adequately support their neurodevelopmental needs. Kangaroo Care (KC) is an evidence-based developmental care strategy that has been shown to be associated with improved short and long term neurodevelopmental outcomes for preterm infants. Despite evidence for best practice, uptake of the practice of KC in resource supported settings remains low. The aim of this study was to identify and describe healthcare providers' perspectives on the barriers and enablers of implementing KC. METHODS: This qualitative study was set in 11 NICUs in British Columbia, Canada, ranging in size from 6 to 70 beds, with mixed levels of care from the less acute up to the most complex acute neonatal care. A total of 35 semi-structured healthcare provider interviews were conducted to understand their experiences providing KC in the NICU. Data were coded and emerging themes were identified. The Consolidated Framework for Implementation Research (CFIR) guided our research methods. RESULTS: Four overarching themes were identified as barriers and enablers to KC by healthcare providers in their particular setting: 1) the NICU physical environment; 2) healthcare provider beliefs about KC; 3) clinical practice variation; and 4) parent presence. Depending on the specific features of a given site these factors functioned as an enabler or barrier to practicing KC. CONCLUSIONS: A 'one size fits all' approach cannot be identified to guide Kangaroo Care implementation as it is a complex intervention and each NICU presents unique barriers and enablers to its uptake. Support for improving parental presence, shifting healthcare provider beliefs, identifying creative solutions to NICU design and space constraints, and the development of a provincial guideline for KC in NICUs may together provide the impetus to change practice and reduce barriers to KC for healthcare providers, families, and administrators at local and system levels.

Neisseria meningitidis expresses a single 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase that is inhibited primarily by phenylalanine.

Neisseria meningitidis is the causative agent of meningitis and meningococcal septicemia is a major cause of disease worldwide, resulting in brain damage and hearing loss, and can be fatal in a large proportion of cases. The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first reaction in the shikimate pathway leading to the biosynthesis of aromatic metabolites including the aromatic acids l-Trp, l-Phe, and l-Tyr. This pathway is absent in humans, meaning that enzymes of the pathway are considered as potential candidates for therapeutic intervention. As the entry point, feedback inhibition of DAH7PS by pathway end products is a key mechanism for the control of pathway flux. The structure of the single DAH7PS expressed by N. meningitidis was determined at 2.0 Å resolution. In contrast to the other DAH7PS enzymes, which are inhibited only by a single aromatic amino acid, the N. meningitidis DAH7PS was inhibited by all three aromatic amino acids, showing greatest sensitivity to l-Phe. An N. meningitidis enzyme variant, in which a single Ser residue at the bottom of the inhibitor-binding cavity was substituted to Gly, altered inhibitor specificity from l-Phe to l-Tyr. Comparison of the crystal structures of both unbound and Tyr-bound forms and the small angle X-ray scattering profiles reveal that N. meningtidis DAH7PS undergoes no significant conformational change on inhibitor binding. These observations are consistent with an allosteric response arising from changes in protein motion rather than conformation, and suggest ligands that modulate protein dynamics may be effective inhibitors of this enzyme.

High diastereoselectivity in borohydride reductions of coordinated imines.

Borohydride reduction of the imine groups in a pyruvate-derived cobalt(III) complex, (OC-6-33')-[Co(Aim(2)trien)](2)[ZnCl(4)], occurs with high diastereoselectivity. The major diastereoisomeric product, (OC-6-33'-ARSSR,CSRRS)-[Co(A(2)trien)]Cl has been isolated and crystallographically characterised. The results from base-induced isomerisation of the major isomer allow us to conclude that most of the remaining material from the reduction reactions (consisting of minor diastereoisomers) differs from the major isomer only in the relative configuration of the coordinated amines. Therefore the initial borohydride attack on the imine groups must have occurred predominantly on the same face of each imine as that which produces the major isomer. The diastereoselectivity of the reaction can be rationalised by proposing hydrogen bonding interactions between the incoming hydride reagent and other donor groups in the complex.