Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis

There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.     

Aged Residential Care Health Utilisation Study (ARCHUS): a randomised controlled trial to reduce acute hospitalisations from residential aged care

ABSTRACT: BACKGROUND: For residents of long term care, hospitalisations can cause distress and disruption, and often result in further medical complications. Multi-disciplinary team interventions have been shown to improve the health of Residential Aged Care (RAC) residents, decreasing the need for acute hospitalisation, yet there are few randomised controlled trials of these complex interventions. This paper describes a randomised controlled trial of a structured multi-disciplinary team and gerontology nurse specialist (GNS) intervention aiming to reduce residents' avoidable hospitalisations. METHODS: This Aged Residential Care Healthcare Utilisation Study (ARCHUS) is a cluster- randomised controlled trial (n = 1700 residents) of a complex multi-disciplinary team intervention in long-term care facilities. Eligible facilities certified for residential care were selected from those identified as at moderate or higher risk of resident potentially avoidable hospitalisations by statistical modelling. The facilities were all located in the Auckland region, New Zealand and were stratified by District Health Board (DHB).InterventionThe intervention provided a structured GNS intervention including a baseline facility needs assessment, quality indicator benchmarking, a staff education programme and care coordination. Alongside this, three multi-disciplinary team (MDT) meetings were held involving a geriatrician, facility GP, pharmacist, GNS and senior nursing staff.OutcomesHospitalisations are recorded from routinely-collected acute admissions during the 9-month intervention period followed by a 5-month follow-up period. ICD diagnosis codes are used in a pre-specified definition of potentially reducible admissions. DISCUSSION: This randomised-controlled trial will evaluate a complex intervention to increase early identification and intervention to improve the health of residents of long term care. The results of this trial are expected in early 2013.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN 12611000187943.     

Extreme chromosome 17 copy number instability is a prognostic factor in patients with gastroesophageal adenocarcinoma: A retrospective cohort study

Gastric and esophageal cancers frequently show genomic instability and aneuploidy. Chromosomal copy number instability (CIN) is a form of genomic instability that exerts pleiotropic effects on cellular biology and is a source of genetic heterogeneity in a population of cells. CIN results in cell‐to‐cell variation in chromosome copy number which can be detected and quantified by fluorescence in situ hybridization (FISH). CIN is a biomarker associated with differential response to a number of chemotherapy compounds. We quantified chromosome 17 copy number instability (CIN‐17) in 348 gastroesophageal adenocarcinomas by centromeric FISH in cases that were tested for HER2 amplification. We evaluated the association between CIN‐17 and clinical outcome after surgical and nonsurgical treatment. CIN‐17 was detected in 45.4% (158/348) and extreme CIN‐17 in 28.4% (99/348). Extreme CIN‐17 had no association with outcome in surgically treated patients. However, in patients treated with conventional radiation and/or chemotherapy, extreme CIN‐17 was associated with 55% reduction in overall mortality (hazard ratio, 0.448; 95% confidence interval, 0.263–0.763) after adjusting for age and clinical stage at diagnosis. Extreme CIN‐17 is detected in over a quarter of gastroesophageal adenocarcinomas and is a favorable prognostic marker in patients treated nonoperatively.     

Implementation of a School-Based Bullying Program

A bully is defined as anyone who participates in any form of repetitive negative and hurtful behavior, with the intent of inflicting harm (Highmark & Center for Safe Schools, 2013). Purpose: The purpose of this project was to evaluate the feasibility of implementing a bullying awareness, prevention, and screening program for teachers and school nurses. Methods: The sample included 174 fifth-graders from a public-school district in rural, southwestern Pennsylvania. Teachers received an educational program and students were screened for bullying using the PIPSQ. Results: Although not a significant finding, there was an increase in teacher’s knowledge post-education (p = 0.515). Although findings were not significant, the results of the PIPSQ revealed greater victimization in this school (M = 6.93), with bullying behaviors greater among boys (p = 0.000). Conclusions: The educational program and the PIPSQ tool appear to be a promising method to identify victimization and bullying within an elementary school setting; further research can determine significance of screening and faculty education.     

Early Experiences of Threat,but Not Deprivation,Are Associated With Accelerated Biological Aging in Children and Adolescents

Background

Recent conceptual models argue that early life adversity (ELA) accelerates development, which may contribute to poor mental and physical health outcomes. Evidence for accelerated development in youths comes from studies of telomere shortening or advanced pubertal development following circumscribed ELA experiences and neuroimaging studies of circuits involved in emotional processing. It is unclear whether all ELA is associated with accelerated development across global metrics of biological aging or whether this pattern emerges following specific adversity types.