Submucosal lingualplasty for adult obstructive sleep apnea.

Objective: To measure quality-of-life outcomes, polysomnographic outcomes, and adverse effects for a new technique of tongue reduction in obstructive sleep apnea.

Study Design: Case series.

Setting: Tertiary hospital.

Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT.

A library of 1,4-benzodiazepines has been synthesised and evaluated for activity against Trypanosoma brucei, a causative parasite of Human African Trypanosomiasis (HAT). The most potent of these derivatives has an MIC value of 0.97 μM.

Design and synthesis of EGFR dimerization inhibitors and evaluation of their potential in the treatment of psoriasis.

Hit compounds from in silico screening for inhibitors of the EGFR dimerization process were evaluated for their anti-proliferative (CCD-1106 keratinocytes) and anti-oxidant (TBA assay) activity and their effect on EGFR dimerization (BS(3) chemical crosslinking assay). 7-Benzyl-8-{N'-[1-(3-ethoxy-4-hydroxyphenyl)meth-(Z)-ylidene]hydrazino}-1,3-dimethylxanthine 2a (127 μM) leads to 37% inhibition of p-EGFR dimerization in the CCD-1106 cell line and also inhibits phosphorylation of proteins in the MAPK/ERK pathway, ERK 1/2 and p-38. Based on this initial data, 2a was selected for further study and was evaluated for its anti-proliferative activity in a range of keratinocyte (CCD-1106, HaCaT and NHEK) and monocyte (ThP1 and U937) cell lines.

Exposure to fire setting behavior on YouTube.

Purpose: This study is a preliminary examination of fire setting behaviors on YouTube.

Methods: Data are based on a 1 day search of YouTube.

Results: Results indicate YouTube is replete with inappropriate models of fire setting.

Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis.

Desbuquois dysplasia (DD) is characterized by antenatal and postnatal short stature, multiple dislocations, and advanced carpal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. We have identified mutations in calcium activated nucleotidase 1 gene (CANT1) in DD type 1.

Retrotransposons control fruit-specific, cold-dependent accumulation of anthocyanins in blood oranges.

Traditionally, Sicilian blood oranges (Citrus sinensis) have been associated with cardiovascular health, and consumption has been shown to prevent obesity in mice fed a high-fat diet. Despite increasing consumer interest in these health-promoting attributes, production of blood oranges remains unreliable due largely to a dependency on cold for full color formation. We show that Sicilian blood orange arose by insertion of a Copia-like retrotransposon adjacent to a gene encoding Ruby, a MYB transcriptional activator of anthocyanin production.

Nuclear factor κB predicts poor outcome in patients with hormone-naive prostate cancer with high nuclear androgen receptor.

Despite recent advances in prostate cancer treatments, disease recurrence is common and associated with significant morbidity and mortality. The need for more effective antitumor agents has led researchers to target signaling pathways that drive tumorigenesis by modulating or bypassing androgen receptor signaling--attenuation or blockade of which current treatments aim to effect. The transcription factor nuclear factor κB/p65 has been implicated in prostate cancer progression; however, few studies have examined the involvement of nuclear factor κB in hormone-naive disease.

Prasugrel versus clopidogrel antiplatelet therapy after acute coronary syndrome: matching treatments with patients.

Antithrombotic therapy is imperative in the management of patients presenting with an acute coronary syndrome (ACS). The combination of antiplatelet therapy in conjunction with antithrombotic therapy has become the standard of care in improving the morbidity and mortality of patients with an ACS and in reducing ischemic complications of percutaneous coronary intervention. Patients with an ACS are at increased risk for a recurrent event, both in-hospital and for several months afterward.

Triphenylbutanamines: kinesin spindle protein inhibitors with in vivo antitumor activity.

The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-l-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold.

Single-incision laparoscopic cholecystectomy with routine intraoperative cholangiography and common bile duct exploration via the umbilical port.

Background: Laparoscopic cholecystectomy currently is the gold standard technique for gallbladder removal. The use of routine intraoperative cholangiography (IOC) is widely practiced during conventional four-port laparoscopic cholecystectomy (4PLC) to confirm biliary anatomy and allow for immediate management of unexpected choledocholithiasis. Single-incision laparoscopic surgery (SILS) offers a more aesthetic technique for gallbladder removal and has been reported by several groups.

Legislative solutions to unhealthy eating and obesity in Australia.

This paper discusses legislative interventions that have potential to address factors in the food environment that contribute to unhealthy eating patterns and increasing obesity rates in the Australian population, and political barriers to the implementation of these interventions. The paper devotes particular attention to legislative interventions to require disclosure of nutrition information about food and beverage products, which would help to inform consumer choices, and are, therefore, difficult to object to on personal responsibility or 'nanny state' grounds. It is suggested that these interventions seem to be gaining political acceptance in Australia, and may provide a starting point for incremental progress.

Manganese dioxide mediated one-pot synthesis of methyl 9H-pyrido[3,4-b]indole-1-carboxylate: Concise synthesis of alangiobussinine.

The carboline ring system is an important pharmacophore found in a number of biologically important targets. Development of synthetic routes for the preparation of these compounds is important in order to prepare a range of analogues containing the carboline heterocyclic moiety. A manganese dioxide mediated one-pot method starting with an activated alcohol and consisting of alcohol oxidation, Pictet-Spengler cyclisation, and oxidative aromatisation, offers a convenient process that allows access to β-carbolines.

Surgical research elective in the United States: an Australian medical student's experience.

The value of surgical research is increasingly recognised by undergraduate medical students interested in pursuing a surgical career. This article describes how an undergraduate medical student from Monash University built upon his surgical research experience from the Eastern Health Surgical Research Group in Australia, by undertaking a 9-week research elective at the Johns Hopkins Center of Surgery Trials and Outcomes Research. Practical issues encountered, such as visa and housing, are outlined.

Amide isosteres in structure-activity studies of antibacterial minor groove binders.

Antibacterial minor groove binders related to the natural product, distamycin, are development candidates for novel antibiotics. Alkenes have been found to be effective substitutes for the isosteric amide links in some positions and alkyl groups larger than methyl have been found to increase binding to DNA in both selectivity and affinity. However the impact of other isosteres such as diazenes and the position of an alkyl group with respect to DNA binding and antibacterial activity are not known.

Starting out - Useful lesson in responding to needs of patient with dementia.

During one of my placements I looked after a patient with dementia who had been admitted to the ward for vascular investigation.

Clinical equipoise in sleep surgery: investigating clinical trial targets.

Objective: Surgical approaches for alleviating snoring and/or obstructive sleep apnea (OSA) have been questioned because of a lack of evidence from high-quality randomized controlled trials (RCTs). An ethical requirement for RCTs is that they must test questions where community equipoise (ie, uncertainty) exists as to the correct treatment. We aimed to measure perceived importance, community equipoise, and willingness to enroll patients in 5 potential trial targets among members of the Australian Society for Otolaryngology Head and Neck Surgery (ASOHNS).

Synthesis and biological evaluation of 1,4-benzodiazepin-2-ones with antitrypanosomal activity.

A library of 1,4-benzodiazepines has been synthesized and evaluated against Trypanosoma brucei, a causative parasite of Human African trypanosomiasis. Benzodiazepines possessing a P2- transporter motif were found to have MIC values as low as 0.78 μM.

Herpes simplex virus type 1 helicase-primase: DNA binding and consequent protein oligomerization and primase activation.

The heterotrimeric helicase-primase complex of herpes simplex virus type I (HSV-1), consisting of UL5, UL8, and UL52, possesses 5' to 3' helicase, single-stranded DNA (ssDNA)-dependent ATPase, primase, and DNA binding activities. In this study we confirm that the UL5-UL8-UL52 complex has higher affinity for forked DNA than for ssDNA and fails to bind to fully annealed double-stranded DNA substrates. In addition, we show that a single-stranded overhang of greater than 6 nucleotides is required for efficient enzyme loading and unwinding.

Ranking ligand affinity for the DNA minor groove by experiment and simulation.

The structural and thermodynamic basis for the strength and selectivity of the interactions of minor groove binders (MGBs) with DNA is not fully understood. In 2003, we reported the first example of a thiazole-containing MGB that bound in a phase-shifted pattern that spanned six base pairs rather than the usual four (for tricyclic distamycin-like compounds). Since then, using DNA footprinting, NMR spectroscopy, isothermal titration calorimetry, and molecular dynamics, we have established that the flanking bases around the central four being read by the ligand have subtle effects on recognition.

The molecular basis for venation patterning of pigmentation and its effect on pollinator attraction in flowers of Antirrhinum.

Pigment stripes associated with veins (venation) is a common flower colour pattern. The molecular genetics and function of venation were investigated in the genus Antirrhinum, in which venation is determined by Venosa (encoding an R2R3MYB transcription factor). Pollinator preferences were measured by field tests with Antirrhinum majus.

Interdisciplinary knowledge translation: lessons learned from a mental health: fire service collaboration.

Collaborative approaches are being increasingly advocated for addressing a variety of health, mental health and social needs for children, youth and families. Factors important for effective knowledge translation of collaborative approaches of service delivery across disciplines, however, have not been rigorously examined. TAPP-C: The Arson Prevention Program for Children is an intervention program for child and adolescent firesetters provided collaboratively by fire service and mental health professionals.

Leucocytoclastic and renal vasculitis in a patient with autoimmune pancreatitis: new associations.

Autoimmune pancreatitis (AIP) is an uncommon condition which comprises diffuse or discrete pancreatic enlargement and irregular pancreatic duct strictures of autoimmune origin leading to pain or obstructive jaundice associated with extra-pancreatic manifestations. It is characterized by an elevated IgG, especially IgG4, level. We illustrate the first described case of a patient with AIP in association with leucocytoclastic and renal vasculitis.