Synthesis and Selective Functionalization of Thiadiazine 1,1-Dioxides with Efficacy in a Model of Huntington's Disease.

The scope of the acid-mediated 3-component synthesis of thiadiazines was investigated. A selective functionalization of the six-membered heterocyclic core structure was accomplished by sequential alkylations, saponifications, and coupling reactions. Several new analogs of a dihydropyrimidinone Hsp70 chaperone agonist, MAL1-271, showed promising activity in a cell based model of Huntington's disease.

The first intramolecular silene Diels-Alder reactions.

The synthesis of silaheterocycles through the first examples of an intramolecular silene Diels-Alder reaction is described.

Oral hygiene care in the pediatric intensive care unit: practice recommendations.

Oral hygiene significantly affects children's well being. It is an integral part of intensive and critical care nursing because intubated and ventilated children in the Pediatric Intensive Care Unit (PICU) are dependent on the health care team to tend to their everyday basic needs. Fourteen articles were identified as being relevant to pediatric oral care in the PICU. These articles were subsequently appraised, and an oral hygiene in the PICU guideline was developed. Research highlighted the relationship between poor oral hygiene in the intensive care unit (ICU) and an increase in dental plaque accumulation, bacterial colonization of the oropharynx, and higher nosocomial infection rates, particularly ventilator-associated pneumonia. Research and a local, informal audit found the provision of oral hygiene care to PICU children varied widely and was often inadequate. Children in the PICU need their mouths regularly assessed and cleaned. Maintaining consistent, regular, and standardized oral hygiene practices in the PICU will also set an example for children and their families, encouraging and teaching them about the life-long importance of oral hygiene.

The implementation and evaluation of an oral healthcare best practice guideline in a paediatric hospital.

The oral health of the New Zealand population now compares unfavourably with other countries. A number of strategies have been introduced at a government and health provider level to improve the oral health status of children. One such strategy was the introduction of a recommended best practice (RBP) within Starship Children's Hospital. Nursing practice was evaluated 2 weeks prior and 6 months post-implementation of the RBP using a survey technique. While there was no significant change in practice post-introduction of the RBP, awareness regarding the oral health care needs of children while in hospital has been improved. This study provides increased understanding in regard to the oral healthcare practices of paediatric nurses, the influences on evidence-based practice change and health education and promotion within an acute paediatric hospital.

Factor Xa inhibitors: S1 binding interactions of a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides.

Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation.