Medicine and Health Sciences Commons^™

First-In-Human Phase I Study Of Infusional And Bolus Schedules Of Deflexifol, A Novel 5-Fluorouracil And Leucovorin Formulation, After Failure Of Standard Treatment, Phillip R. Clingan, Stephen Ackland, Daniel Brungs, Paul De Souza, Morteza Aghmesheh, Madhu Garg, Richard Ranson, Suzanne Parker, Rebecca Jokela, Marie Ranson

Illawarra Health and Medical Research Institute

Background: 5‐Fluorouracil (5‐FU) is administered with leucovorin (LV) to enhance clinical activity. However, simultaneous administration is not feasible due to their chemical incompatibility, so conditions for the maximum possible beneficial interaction cannot be met. To overcome this, we developed a novel all‐in‐one, pH neutral stable solution of 5‐FU plus LV with β‐cyclodextrin (termed Deflexifol) and assessed its safety and tolerability in a first‐in‐human phase I trial.

Methods: Patients with advanced solid malignancy received Deflexifol as weekly bolus (375–575 mg/m²) or two‐weekly 46 h infusion (1200–3600 mg/m²) for six cycles in a 3+3 dose escalation design. …

A Systematic Review Of Food Composition Tools Used For Determining Dietary Polyphenol Intake In Estimated Intake Studies, Yasmine Probst, Vivienne Guan, Katherine Caldwell

Illawarra Health and Medical Research Institute

Translating food intake data into phytochemical outcomes is a crucial step in investigating potential health benefits. The aim of this review was to examine the tools for determining dietary-derived polyphenol intakes for estimated intake studies. Published studies from 2004 to 2014 reporting polyphenol food composition information were sourced with 157 studies included. Six polyphenol subclasses were identified. One quarter of studies (n = 39) reported total flavonoids intake with 27% reporting individual flavonoid compounds. Assessing multiple compounds was common with approximately 10% of studies assessing seven (n = 13), six (n = 12) and five (n = 14) subclasses of …

Regulatory Effects Of Simvastatin And Apoj On App Processing And Amyloid-Β Clearance In Blood-Brain Barrier Endothelial Cells, Martina Zandl-Lang, Elham Fanaee-Danesh, Yidan Sun, Nicole Albrecher, Chaitanya Chakravarthi Gali, Igor Cancar, Alexandra Kober, Carman Tam-Amersdorfer, Anika Stracke, Steffen Storck, Ahmed Saeed, Jasminka Stefulj, Claus Pietrzik, Mark R. Wilson, Ingemar Björkhem, Ute Panzenboeck

Illawarra Health and Medical Research Institute

Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer's disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients. ApoJ may bind, prevent fibrillization, and enhance clearance of Aβ. We here define a connection of apoJ and cellular cholesterol homeostasis in …

Effects Of Short- And Long-Term Aripiprazole Treatment On Group I Mglurs In The Nucleus Accumbens: Comparison With Haloperidol, Jeremy Lum, Bo Pan, Chao Deng, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell

Illawarra Health and Medical Research Institute

The D2 receptor partial agonist, aripiprazole, has shown increased therapeutic efficacy for schizophrenia, autism and Tourette's syndrome compared to traditional antipsychotics such as the D2 receptor antagonist, haloperidol. Recent evidence suggests this superior profile may be associated with downstream effects on glutamatergic synapses. Group 1 metabotropic glutamate receptors (mGluRs) and their endogenous modulators, Norbin and Homer1, are regulated by D2 receptor activity, particularly within the nucleus accumbens (NAc), a target region of aripiprazole and haloperidol. This study sought to evaluate the effects of aripiprazole on Group 1 mGluRs, Norbin and Homer1 in the NAc, in comparison to haloperidol. Sprague-Dawley rats …

Computer-Aided Design Of Human Sialyltransferase Inhibitors Of Hst8sia Iii, Christopher Dobie, Andrew Montgomery, Remi Szabo, Danielle Skropeta, Haibo Yu

Illawarra Health and Medical Research Institute

Sialyltransferase (ST) upregulation and the resultant hypersialylation of tumour cell surfaces is an established hallmark of many cancers including lung, breast, ovarian, pancreatic and prostate cancer. The role of ST enzymes in tumour cell growth and metastasis, as well as links to multi-drug resistance, has seen ST inhibition emerge as a target for potential antimetastatic cancer treatments. The most potent of these reported inhibitors are transition-state analogues. Although there are several examples of these in the literature, many have suspected poor pharmacokinetic properties and are not readily synthetically accessible. A proposed solution to these problems is the use of a …

Detection Of Kinetic Change Points In Piece-Wise Linear Single Molecule Motion, Flynn R. Hill, Antoine M. Van Oijen, Karl E. Duderstadt

Illawarra Health and Medical Research Institute

Single-molecule approaches present a powerful way to obtain detailed kinetic information at the molecular level. However, the identification of small rate changes is often hindered by the considerable noise present in such single-molecule kinetic data. We present a general method to detect such kinetic change points in trajectories of motion of processive single molecules having Gaussian noise, with a minimum number of parameters and without the need of an assumed kinetic model beyond piece-wise linearity of motion. Kinetic change points are detected using a likelihood ratio test in which the probability of no change is compared to the probability of …

Phenotypic And Functional Characterization Of Peripheral Sensory Neurons Derived From Human Embryonic Stem Cells, Abdullah J. Alshawaf, Serena Viventi, Wanzhi Qiu, Giovanna M. D'Abaco, Bryony A. Nayagam, Michael Erlichster, Gursharan Chana, Ian Everall, Jason Ivanusic, Efstratios Skafidas, Mirella Dottori

Illawarra Health and Medical Research Institute

The dorsal root ganglia (DRG) consist of a multitude of sensory neuronal subtypes that function to relay sensory stimuli, including temperature, pressure, pain and position to the central nervous system. Our knowledge of DRG sensory neurons have been predominantly driven by animal studies and considerably less is known about the human DRG. Human embryonic stem cells (hESC) are valuable resource to help close this gap. Our previous studies reported an efficient system for deriving neural crest and DRG sensory neurons from hESC. Here we show that this differentiation system gives rise to heterogeneous populations of sensory neuronal subtypes as demonstrated …

Osteoclast Inhibitors To Prevent Bone Metastases In Men With High-Risk, Nonmetastatic Prostate Cancer: A Systematic Review And Meta-Analysis, Aimee R. Hayes, Daniel Brungs, Nick Pavlakis

Illawarra Health and Medical Research Institute

Background: In advanced prostate cancer, osteoclast inhibitors prevent and palliate skeletal related events associated with bone metastases. However, it is uncertain whether they play a disease-modifying role earlier in the course of the disease.

Methods: Medline, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and ASCO conference proceedings were searched for randomized controlled trials that compared osteoclast inhibitors with placebo and/or standard of care (SOC) in patients with high-risk, non-metastatic prostate cancer. The primary outcome measure was incidence of new bone metastases; secondary outcomes included overall survival (OS), prostate cancer specific survival, mortality unrelated to …

Cyclic Analogues Of Α-Conotoxin Vc1.1 Inhibit Colonic Nociceptors And Provide Analgesia In A Mouse Model Of Chronic Abdominal Pain, Joel Castro, Luke Grundy, Annemie Deiteren, Andrea M. Harrington, Tracey O'Donnell, Jessica Maddern, Jessi Moore, Sonia Garcia-Caraballo, Grigori Rychkov, Rilei Yu, Quentin Kaas, David J. Craik, David J. Adams, Stuart Brierley

Illawarra Health and Medical Research Institute

Background and Purpose: Patients with irritable bowel syndrome suffer from chronic visceral pain (CVP) and limited analgesic therapeutic options are currently available. We have shown that α-conotoxin Vc1.1 induced activation of GABA_B receptors on the peripheral endings of colonic afferents and reduced nociceptive signalling from the viscera. However, the analgesic efficacy of more stable, cyclized versions of Vc1.1 on CVP remains to be determined.

Experimental Approach: Using ex vivo colonic afferent preparations from mice, we determined the inhibitory actions of cyclized Vc1.1 (cVc1.1) and two cVc1.1 analogues on mouse colonic nociceptors in healthy and chronic visceral hypersensitivity …

Generation Of Rab39b Knockout Isogenic Human Embryonic Stem Cell Lines To Model Rab39b-Mediated Parkinson's Disease, Yujing Gao, Gabrielle Wilson, Kiymet Bozaoglu, Andrew Elefanty, Edouard Stanley, Mirella Dottori, Paul J. Lockhart

Illawarra Health and Medical Research Institute

Mutations in RAB39B are a known cause of X-linked early onset Parkinson's disease. Isogenic human embryonic stem cell lines carrying two independent deletions of RAB39B were generated using CRISPR/Cas9 genome editing tool. The deletions were confirmed by PCR and direct sequence analysis in two edited stem cell lines. Both cell lines showed pluripotency and displayed a normal karyotype. Further, they were able to form embryoid bodies in vitro, and express markers indicative of differentiation to the three germ layers.

Cryopreservation For Delayed Circulating Tumor Cell Isolation Is A Valid Strategy For Prognostic Association Of Circulating Tumor Cells In Gastroesophageal Cancer, Daniel Brungs, David Lynch, Alison Luk, Elahe Minaei, Marie Ranson, Morteza Aghmesheh, Kara L. Vine, Martin G. Carolan, Mouhannad Jaber, Paul De Souza, Therese M. Becker

Illawarra Health and Medical Research Institute

AIM: To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells (PBMCs) for prognostic circulating tumor cell (CTC) detection in gastroesophageal cancer.

METHODS: Using 7.5 mL blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule based immunomagnetic capture using the IsoFlux platform. Paired specimens taken during the same blood draw (n = 15) were used to compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples were processed within 24 h to recover the PBMC fraction, with PBMCs used for fresh analysis immediately processed for …

Graphene Foam As A Biocompatible Scaffold For Culturing Human Neurons, Giovanna M. D'Abaco, Cristiana Mattei, Babak Nasr, Emma J. Hudson, Abdullah J. Alshawaf, Gursharan Chana, Ian Everall, Bryony A. Nayagam, Mirella Dottori, Efstratios Skafidas

Illawarra Health and Medical Research Institute

In this study, we explore the use of electrically active graphene foam as a scaffold for the culture of human-derived neurons. Human embryonic stem cell (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic neuronal phenotypes were cultured on graphene foam. We show that graphene foam is biocompatible for the culture of human neurons, capable of supporting cell viability and differentiation of hESC-derived cortical neurons. Based on the findings, we propose that graphene foam represents a suitable scaffold for engineering neuronal tissue and warrants further investigation as a model for understanding neuronal maturation, function and circuit formation.

Attaching Nora Efflux Pump Inhibitors To Methylene Blue Enhances Antimicrobial Photodynamic Inactivation Of Escherichia Coli And Acinetobacter Baumannii In Vitro And In Vivo, Ardeshir Rineh, John B. Bremner, Michael R. Hamblin, Anthony R. Ball, George P. Tegos, Michael J. Kelso

Illawarra Health and Medical Research Institute

Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness. We recently reported the discovery of a NorA efflux pump inhibitor-methylene blue (EPI-MB) hybrid compound INF55-(Ac)en-MB that shows enhanced photodynamic inactivation of …

Towards Clinical Translation Of Ligand-Functionalized Liposomes In Targeted Cancer Therapy: Challenges And Opportunities, Lisa Belfiore, Darren N. Saunders, Marie Ranson, Kristofer Thurecht, Gert Storm, Kara L. Vine

Illawarra Health and Medical Research Institute

The development of therapeutic resistance to targeted anticancer therapies remains a significant clinical problem, with intratumoral heterogeneity playing a key role. In this context, improving the therapeutic outcome through simultaneous targeting of multiple tumor cell subtypes within a heterogeneous tumor is a promising approach. Liposomes have emerged as useful drug carriers that can reduce systemic toxicity and increase drug delivery to the tumor site. While clinically used liposomal drug formulations show marked therapeutic advantages over free drug formulations, ligand-functionalized liposomes that can target multiple tumor cell subtypes may further improve the therapeutic efficacy by facilitating drug delivery to a broader …

The Small Heat Shock Protein Hsp27 Binds Α-Synuclein Fibrils, Preventing Elongation And Cytotoxicity, Dezerae Cox, Daniel Whiten, James W. P Brown, Mathew H. Horrocks, Rebecca San Gil, Christopher M. Dobson, David Klenerman, Antoine M. Van Oijen, Heath Ecroyd

Illawarra Health and Medical Research Institute

Proteostasis, or protein homeostasis, encompasses the maintenance of the conformational and functional integrity of the proteome and involves an integrated network of cellular pathways. Molecular chaperones, such as the small heat shock proteins (sHsps), are key elements of the proteostasis network that have crucial roles in inhibiting the aggregation of misfolded proteins. Failure of the proteostasis network can lead to the accumulation of misfolded proteins into intracellular and extracellular deposits. Deposits containing fibrillar forms of α-sy-nuclein (α-syn) are characteristic of neurodegenerative disorders including Parkinson's disease and dementia with Lewy bodies. Here we show that the sHsp Hsp27 (HSPB1) binds to …

Development And Optimization Of Ciprofloxacin-Loaded Gelatin Microparticles By Single-Step Spray-Drying Technique, Dina M. Morais Da Silva, Heema Vyas, Martina L. Sanderson-Smith, Vitor Sencadas

Illawarra Health and Medical Research Institute

Polymeric particles are a versatile class of local or systemic drug delivery systems, used to improve drugs pharmacokinetics and pharmacodynamics along with patient compliance. Herein, we report a rapid, scalable, and optimized method to encapsulate ciprofloxacin (CP_x), a poor water soluble antimicrobial agent, in gelatin microparticles by single step processing via spray-drying of an aqueous solution. The developed particles show mainly a wrinkle morphology with a unimodal distribution, with mean diameters ranging between 2 and 4 μm, depending on the processing conditions. The encapsulation of 1, 2 and 5 wt% CPx narrows the size distribution (1-3 μm). In …

Exploring Data Quality Management Within Clinical Trials, Lauren Houston, Yasmine Probst, Ping Yu, Allison Martin

Illawarra Health and Medical Research Institute

Background Clinical trials are an important research method for improving medical knowledge and patient care. Multiple international and national guidelines stipulate the need for data quality and assurance. Many strategies and interventions are developed to reduce error in trials, including standard operating procedures, personnel training, data monitoring, and design of case report forms. However, guidelines are nonspecific in the nature and extent of necessary methods.

Objective This article gathers information about current data quality tools and procedures used within Australian clinical trial sites, with the aim to develop standard data quality monitoring procedures to ensure data integrity.

Methods Relevant information …

The Influence Of The N-Terminal Region Proximal To The Core Domain On The Assembly And Chaperone Activity Of Αb-Crystallin, Blagojce Jovcevski, John Andrew Aquilina, Justin Benesch, Heath Ecroyd

Illawarra Health and Medical Research Institute

αB-Crystallin (HSPB5) is a small heat-shock protein that is composed of dimers that then assemble into a polydisperse ensemble of oligomers. Oligomerisation is mediated by heterologous interactions between the C-terminal tail of one dimer and the core "α-crystallin" domain of another and stabilised by interactions made by the N-terminal region. Comparatively little is known about the latter contribution, but previous studies have suggested that residues in the region 54-60 form contacts that stabilise the assembly. We have generated mutations in this region (P58A, S59A, S59K, R56S/S59R and an inversion of residues 54-60) to examine their impact on oligomerisation and chaperone …

Creation Of A Fibre Categories Database To Quantify Different Dietary Fibres, Stacey Fuller, Linda C. Tapsell, Eleanor J. Beck

Illawarra Health and Medical Research Institute

Foods rich in dietary fibre have long been consumed for their known health benefits. Fibre represents a complex group of substances, with diverse physicochemical properties and therefore varied physiological effects. To be able to fully understand the clinical benefit of consuming dietary fibre, it is important to look at the components and their physiological roles. Evidence suggests that soluble fibres contribute to health effects such as blood glucose attenuation and cholesterol lowering, while insoluble fibres play a role in health effects such as laxation. Most countries have a food composition database that includes dietary fibre, however further details on categories …

The Impact Of Caller Gender On Telephone Crisis-Helpline Workers' Interpretation Of Suicidality In Caller Vignettes, Tara Hunt, Coralie J. Wilson, Peter Caputi, Ian G. Wilson, Alan Woodward

Illawarra Health and Medical Research Institute

Telephone crisis-line workers (TCWs) are trained in a variety of techniques and skills to facilitate the identification of suicidal callers. One factor that may influence the implementation of these skills is gender. This study used an experimental design to explore whether helpline callers being identified as male or female is associated with TCWs' ratings of callers' potential for suicide risk and TCWs' intention to use support- or intervention-oriented skills with callers. Data were collected using an online self-report survey in an Australian sample of 133 TCWs. The results suggest that under some circumstances the callers' gender might influence TCWs' intention …

The Transcription-Repair Coupling Factor Mfd Associates With Rna Polymerase In The Absence Of Exogenous Damage, Han Ngoc Ho, Antoine M. Van Oijen, Harshad Ghodke

Illawarra Health and Medical Research Institute

During transcription elongation, bacterial RNA polymerase (RNAP) can pause, backtrack or stall when transcribing template DNA. Stalled transcription elongation complexes at sites of bulky lesions can be rescued by the transcription terminator Mfd. The molecular mechanisms of Mfd recruitment to transcription complexes in vivo remain to be elucidated, however. Using single-molecule live-cell imaging, we show that Mfd associates with elongation transcription complexes even in the absence of exogenous genotoxic stresses. This interaction requires an intact RNA polymerase-interacting domain of Mfd. In the presence of drugs that stall RNAP, we find that Mfd associates pervasively with RNAP. The residence time of …

Quantification Of Ligand Density And Stoichiometry On The Surface Of Liposomes Using Single-Molecule Fluorescence Imaging, Lisa Belfiore, Lisanne M. Spenkelink, Marie Ranson, Antoine M. Van Oijen, Kara L. Vine

Illawarra Health and Medical Research Institute

Despite the longstanding existence of liposome technology in drug delivery applications, there have been no ligand-directed liposome formulations approved for clinical use to date. This lack of translation is due to several factors, one of which is the absence of molecular tools for the robust quantification of ligand density on the surface of liposomes. We report here for the first time the quantification of proteins attached to the surface of small unilamellar liposomes using single-molecule fluorescence imaging. Liposomes were surface-functionalized with fluorescently labeled human proteins previously validated to target the cancer cell surface biomarkers plasminogen activator inhibitor-2 (PAI-2) and trastuzumab …

"Characterization Of Elekta Srs Cone Collimator Using High Spatial Resolution Monolithic Silicon Detector Array", Khalsa Al Shukaili, Stephanie Corde, Marco Petasecca, V Pereveratylo, Michael L. F Lerch, Michael A. Jackson, Anatoly B. Rosenfeld

Illawarra Health and Medical Research Institute

Purpose: To investigate the accuracy of the dosimetry of radiation fields produced by small ELEKTA cone collimators used for stereotactic radiosurgery treatments (SRS) using commercially available detectors EBT3 Gafchromic ^TM film, IBA Stereotactic diode (SFD), and the recently developed detector DUO, which is a monolithic silicon orthogonal linear diode array detector.

Methods: These three detectors were used for the measurement of beam profiles, output factors, and percentage depth dose for SRS cone collimators with cone sizes ranging from 5 to 50 mm diameter. The measurements were performed at 10 cm depth and 90 cm SSD.

Results: The …

Single-Molecule Characterization Of The Interactions Between Extracellular Chaperones And Toxic Α-Synuclein Oligomers, Daniel Whiten, Dezerae Cox, Mathew H. Horrocks, Christopher Taylor, Suman De, Patrick Flagmeier, Laura Tosatto, Janet R. Kumita, Heath Ecroyd, Christopher M. Dobson, David Klenerman, Mark R. Wilson

Illawarra Health and Medical Research Institute

The aberrant aggregation of α-synuclein is associated with several human diseases, collectively termed the α-synucleinopathies, which includes Parkinson's disease. The progression of these diseases is, in part, mediated by extracellular α-synuclein oligomers that may exert effects through several mechanisms, including prion-like transfer, direct cytotoxicity, and pro-inflammatory actions. In this study, we show that two abundant extracellular chaperones, clusterin and α2-macroglobulin, directly bind to exposed hydrophobic regions on the surface of α-synuclein oligomers. Using single-molecule fluorescence techniques, we found that clusterin, unlike α2-macroglobulin, exhibits differential binding to α-synuclein oligomers that may be related to structural differences between two previously described forms …

Perinatal Administration Of Phencyclidine Alters Expression Of Lingo-1 Signaling Pathway Proteins In The Prefrontal Cortex Of Juvenile And Adult Rats, Jessica L. Andrews, Kelly A. Newell, Natalie Matosin, Xu-Feng Huang, Francesca Fernandez-Enright

Illawarra Health and Medical Research Institute

Postnatal administration of phencyclidine (PCP) in rodents causes major brain dysfunction leading to severe disturbances in behavior lasting into adulthood. This model is routinely employed to model psychiatric disorders such as schizophrenia, as it reflects schizophrenia related brain disturbances in cluding increased apoptosis, a nd disruptions to myelin and plasticity processes. Leucine -rich repeat and immunoglobulin domain-containing protein, Lingo-1, is a potent negative regulator of both axonal myelination and neurite extension. The Nogo receptor (NgR)/TNF receptor orphan Y (T ROY) and/or p75 complex, With No Lysine (K) (WNK1) and Myelin transcription factor-1 (Myt1) are co-receptors or co-factors in Lingo- 1 …

Decreased 5‐Ht2cr And Ghsr1a Interaction In Antipsychotic Drug‐Induced Obesity, Xu-Feng Huang, Katrina Weston-Green, Y Yu

Illawarra Health and Medical Research Institute

Second generation antipsychotics (SGAs), notably atypical antipsychotics includingolanzapine, clozapine and risperidone, can cause weight gain and obesity side ef-fects. Antagonism of serotonin 2c receptors (5-HT2cR) and activation of ghrelin re-ceptor type 1a (GHSR1a) signalling have been identified as a main cause of SGAinduced obesity. Here we review the pivotal regulatory role of the 5-HT2cR inghrelin-mediated appetite signalling. The 5-HT2cR dimerizes with GHSR1a to in-hibit orexigenic signalling, while 5-HT2cR antagonism reduces dimerization andincreases GHSR1a-induced food intake. Dimerization is specific to the unedited5-HT2cR isoform. 5-HT2cR antagonism by SGAs may disrupt the normal inhibi-tory tone on the GHSR1a, increasing orexigenic signalling. The 5-HT2cR …

Chronic Adolescent Cdppb Treatment Alters Short-Term, But Not Long-Term, Glutamatergic Receptor Expression, Jeremy Lum, Samuel Millard, Elisabeth T. Frank, Natalie Matosin, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell

Illawarra Health and Medical Research Institute

Dysfunction of the glutamatergic system is believed to underlie many neurodevelopmental disorders including autism, Rett syndrome and schizophrenia. Metabotropic glutamate receptor (mGluR5) positive allosteric modulators (PAM) potentiate glutamatergic signaling, particularly indirectly via the NMDA receptor. Preclinical studies report mGluR5 PAMs can improve schizophrenia-relevant behaviours. Furthermore, adolescent administration has shown to prevent cognitive induced deficits in adult rodents. However, there is limited understanding of the short- and long-term neurochemical effects of mGluR5 PAMs, which may underlie their therapeutic effects. We examined the effect of 7-day adolescent (PN28-34) treatment with the mGluR5 PAM, CDDPB (30 mg/kg), on glutamatergic receptor expression at adolescence …

Identifying Usual Food Choices At Meals In Overweight And Obese Study Volunteers: Implications For Dietary Advice, Vivienne Guan, Yasmine Probst, Elizabeth Neale, Marijka Batterham, Linda C. Tapsell

Illawarra Health and Medical Research Institute

Understanding food choices made for meals in overweight and obese individuals may aid strategies for weight loss tailored to their eating habits. However, limited studies have explored food choices at meal occasions. The aim of this study was to identify the usual food choices for meals of overweight and obese volunteers for a weight-loss trial. A cross-sectional analysis was performed using screening diet history data from a 12-month weight-loss trial (the HealthTrack study). A descriptive data mining tool, the Apriori algorithm of association rules, was applied to identify food choices at meal occasions using a nested hierarchical food group classification …

Inhibition Of Human N- And T-Type Calcium Channels By An Ortho-Phenoxyanilide Derivative, Moniro-1, Jeffrey R. Mcarthur, Leonid Motin, Ellen Gleeson, Sandro Spiller, Richard J. Lewis, Peter J. Duggan, Kellie L. Tuck, David J. Adams

Illawarra Health and Medical Research Institute

Background and Purpose: Voltage-gated calcium channels are involved in nociception in the CNS and in the periphery. N-type (Ca_v2.2) and T-type (Ca_v3.1, Ca_v3.2 and Ca_v3.3) voltage-gated calcium channels are particularly important in studying and treating pain and epilepsy. Experimental Approach: In this study, whole-cell patch clamp electrophysiology was used to assess the potency and mechanism of action of a novel ortho-phenoxylanilide derivative, MONIRO-1, against a panel of voltage-gated calcium channels including Ca_v1.2, Ca_v1.3, Ca_v2.1, Ca_v2.2, Ca_v2.3, Ca_v3.1, Ca …

Predictors For Misreporting Sodium And Potassium Intakes By Overweight And Obese Participants In A Food-Based Clinical Trial: Implications For Practice, Vivienne Guan, Yasmine Probst, Elizabeth Neale, Linda C. Tapsell

Illawarra Health and Medical Research Institute

This study compared self-reported sodium and potassium intakes with urinary biomarkers and identified predictive factors. Secondary analysis of the 3-month intensive phase of the HealthTrack study with control (C), interdisciplinary intervention (I), intervention plus 30 g walnuts/day (IW) arms (n = 149). Dietary data was derived from diet history (DH) interviews and biomarker measures from urine. Urine-derived sodium (all, p = 0.000) and potassium (C: p = 0.011; I: p = 0.000; IW: p = 0.004) measures were significantly greater than self-reported intakes over the three months. Multiple linear regression showed body weight at baseline, body mass index (BMI) at …