Digital Commons Network^™

Is The Australian Smoking Population Hardening?, Tanya Buchanan, Christopher A. Magee, Ezinne Oyidia Igwe, Peter James Kelly

Illawarra Health and Medical Research Institute

Background The hardening hypothesis proposes that as smoking rates decline, the remaining smokers will become hardcore and resistant to quitting. This group of highly resistant quitters will potentially require more individualistic approaches to cessation and harm reduction. The harm reduction approach (specifically e-cigarettes) has been proposed as an option to address hardened Australian smokers. We tested the hardening hypothesis by analysing the rates of hardcore smoking in the Australian smoking population between 2010-2016. Methods Data were drawn from three waves of the National Drug Strategy Household Survey (NDSHS) in 2010, 2013 and 2016. Two different definitions were used to assess …

Ketamine Inhibits Synaptic Transmission And Nicotinic Acetylcholine Receptor-Mediated Responses In Rat Intracardiac Ganglia In Situ, Alexander A. Harper, Katrina Rimmer, Jhansi Dyavanapalli, Jeffrey R. Mcarthur, David J. Adams

Illawarra Health and Medical Research Institute

The intravenous anaesthetic ketamine, has been demonstrated to inhibit nicotinic acetylcholine receptor (nAChR)-mediated currents in dissociated rat intracardiac ganglion (ICG) neurons (Weber et al., 2005). This effect would be predicted to depress synaptic transmission in the ICG and would account for the inhibitory action of ketamine on vagal transmission to the heart (Inoue and König, 1988). This investigation was designed to examine the activity of ketamine on (i) postsynaptic responses to vagal nerve stimulation, (ii) the membrane potential, and (iii) membrane current responses evoked by exogenous application of ACh and nicotine in ICG neurons in situ. Intracellular recordings were made …

Overeating And Food Addiction In Major Depressive Disorder: Links To Peripheral Dopamine, Jessica Mills, Susan J. Thomas, Theresa A. Larkin, Chao Deng

Illawarra Health and Medical Research Institute

The concept of food addiction refers to addiction-like behaviours that develop in association with the intake of highly palatable foods. Previous research indicates that a high proportion of individuals with Major Depressive Disorder (MDD) meet the criteria for food addiction, and are also at an increased risk of weight gain and chronic disease. In the central nervous system, dopamine is a neurotransmitter associated with reward salience and food intake, whereas peripheral dopamine is involved in sympathetic stress regulation, digestion and gastrointestinal motility. However, little research has examined relationships between peripheral dopamine, depressive symptoms and problematic eating behaviours in MDD. Biometrics, …

Fulditoxin, Representing A New Class Of Dimeric Snake Toxins, Defines Novel Pharmacology At Nicotinic Ach Receptors, Chun Foo, Chacko Jobichen, Varuna Hassan-Puttaswamy, Zoltan Dekan, Han Shen Tae, Daniel Bertrand, David J. Adams, Paul Alewood, J Sivaraman, Selvanayagam Nirthanan, R Kini

Illawarra Health and Medical Research Institute

Background and Purpose: Animal toxins have contributed significantly to our understanding of the neurobiology of receptors and ion channels. We studied the venom of the coral snake Micrurus fulvius fulvius and identified and characterized the structure and pharmacology of a new homodimeric neurotoxin, fulditoxin, that exhibited novel pharmacology at nicotinic ACh receptors (nAChRs). Experimental Approach: Fulditoxin was isolated by chromatography, chemically synthesized, its structure determined by X-ray crystallography, and its pharmacological actions on nAChRs characterized by organ bath assays and two-electrode voltage clamp electrophysiology. Key Results: Fulditoxin's distinct 1.95-Å quaternary structure revealed two short-chain three-finger α-neurotoxins (α-3FNTxs) non-covalently bound by …

Marine Toxins Targeting Kv1 Channels: Pharmacological Tools And Therapeutic Scaffolds, Rocio K. Finol Urdaneta, Aleksandra Belovanovic, Milica Micic-Vicovac, Gemma Kinsella, Jeffrey R. Mcarthur, Ahmed Al-Sabi

Illawarra Health and Medical Research Institute

Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential for the treatment of ion channel-related diseases or channelopathies. Here, we review specific peptide and small-molecule marine toxins modulating Kv1 channels and thus cover recent findings of bioactives found in the venoms of marine Gastropod (cone snails), Cnidarian (sea anemones), and small compounds from cyanobacteria. Furthermore, we discuss pivotal advancements at exploiting the interaction of κM-conotoxin RIIIJ …

Priorities For Service Improvement In Personality Disorder In Australia: Perspectives Of Consumers, Carers And Clinicians, Fiona Y. Ng, Michelle L. Townsend, Mahlie Jewell, Ely M. Marceau, Brin F. S Grenyer

Illawarra Health and Medical Research Institute

Personality and Mental Health Published by John Wiley & Sons Ltd Background: Improvements to service provision for personality disorder has been predominately explored through the perspectives of clinicians, with limited understanding of the views of consumers and carers. The aim of the present study was to understand the priorities for service improvement through multiple perspectives. Method: Twelve roundtables, with a total of 53 consumers, clinicians and carers, discussed how organizations could improve service provision for people with personality disorder and completed a questionnaire on current and optimal service provision. Inductive thematic analysis was used to identify the priorities for service …

Interactions Of The Α3Β2 Nicotinic Acetylcholine Receptor Interfaces With Α-Conotoxin Lsia And Its Carboxylated C-Terminus Analogue: Molecular Dynamics Simulations, Jierong Wen, David J. Adams, Andrew Hung

Illawarra Health and Medical Research Institute

Notably, α-conotoxins with carboxy-terminal (C-terminal) amidation are inhibitors of the pentameric nicotinic acetylcholine receptors (nAChRs), which are therapeutic targets for neurological diseases and disorders. The (α3)2(β2)3 nAChR subunit arrangement comprises a pair of α3(+)β2(-) and β2(+)α3(-) interfaces, and a β2(+)β2(-) interface. The β2(+)β2(-) interface has been suggested to have higher agonist affinity relative to the α3(+)β2(-) and β2(+)α3(-) interfaces. Nevertheless, the interactions formed by these subunit interfaces with α-conotoxins are not well understood. Therefore, in order to address this, we modelled the interactions between α-conotoxin LsIA and the α3β2 subtype. The results suggest that the C-terminal carboxylation of LsIA predominantly …

Npy/Npf-Related Neuropeptide Flp-34 Signals From Serotonergic Neurons To Modulate Aversive Olfactory Learning In Caenorhabditis Elegans, Melissa Fadda, Nathan De Fruyt, Charline Borghgraef, Jan Watteyne, Katleen Peymen, Elke Vandewyer, Francisco Naranjo Galindo, Amanda Kieswetter, Olivier Mirabeau, Yee Lian Chew, Isabel Beets, Liliane Schoofs

Illawarra Health and Medical Research Institute

Copyright © 2020 the authors. Aversive learning is fundamental for animals to increase chances of survival. In addition to classical neurotransmitters, neuropeptides have emerged to modulate such complex behaviors. Among them, neuropeptide Y (NPY) is well known to promote aversive memory acquisition in mammals. Here we identify an NPY/neuropeptide F (NPF)-related neuropeptide system in Caenorhabditis elegans and show that this FLP-34/NPR-11 system is required for learning negative associations, a process that is reminiscent of NPY signaling in mammals. The Caenorhabditis elegans NPY/NPF ortholog FLP-34 displays conserved structural hallmarks of bilaterian-wide NPY/NPF neuropeptides. We show that it is required for aversive …

Prevention Of Neurite Spine Loss Induced By Dopamine D2 Receptor Overactivation In Striatal Neurons, Peng Zheng, Qian Su, Dayong Jin, Yinghua Yu, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Psychosis has been considered a disorder of impaired neuronal connectivity. Evidence for excessive formation of dopamine D2 receptor (D2R) – disrupted in schizophrenia 1 (DISC1) complexes has led to a new perspective on molecular mechanisms involved in psychotic symptoms. Here, we investigated how excessive D2R–DISC1 complex formation induced by D2R agonist quinpirole affects neurite growth and dendritic spines in striatal neurons. Fluorescence resonance energy transfer (FRET), stochastic optical reconstruction microscopy (STORM), and cell penetrating-peptide delivery were used to study the cultured striatal neurons from mouse pups. Using these striatal neurons, our study showed that: (1) D2R interacted with DISC1 in …

Association Of A P2rx7 Gene Missense Variant With Brachycephalic Dog Breeds, Reece Sophocleous, Vanessa Sluyter, Belinda L. Curtis, Stephen J. Curtis, Lisa M. Jurak, Megan Faulks, Mari Spildrejorde, S Gates, Emma-Jayne Proctor, Aine Seavers, Debbie Watson, Tracey A. Kuit, Mark P. Dowton, Leanne Stokes, Ronald Sluyter

Illawarra Health and Medical Research Institute

Stichting International Foundation for Animal Genetics Missense variants are associated with various phenotypic traits and disorders in dogs. The canine P2RX7 gene, coding the ATP-gated P2X7 receptor ion channel, contains four known missense variants. The current study aimed to examine the presence of these variants in a random sample of pedigree and mixed-pedigree dogs. Exons 3, 8, 11 and 13 of the P2RX7 gene, encoding these four respective variants, in 65 dogs were assessed by Sanger sequencing and combined with existing sequencing data from another 69 dogs. The distribution of these variants was then evaluated in all 134 dogs combined …

Twelve-Month Outcomes Of Makingthelink: A Cluster Randomized Controlled Trial Of A School-Based Program To Facilitate Help-Seeking For Substance Use And Mental Health Problems, Dan Lubman, Ali Cheetham, Emma Sandral, Rory Wolfe, Catherine Martin, Fiona Blee, Bonita Berridge, Anthony Jorm, Coralie J. Wilson, Nicholas Allen, Lisa Mckay-Brown, Jenny Proimos

Illawarra Health and Medical Research Institute

Background: Young people experiencing mental health problems are often reluctant to seek help, particularly from professionals (i.e., doctors or mental health workers). MAKINGtheLINK is a school-based intervention that aims to help adolescents overcome barriers to seeking professional help for mental health and substance use problems. Methods: A cluster randomised controlled trial was conducted to evaluate the 12-month outcomes of MAKINGtheLINK among 2447 participants (Mean age=14.9 years, SD=0.5 years, 50% male). Randomisation resulted in 1130 students from 11 schools allocated to receive the intervention, and 1317 students from 10 schools allocated to the wait-list control group. After the baseline assessment, follow-ups …

Issfal Official Statement Number 6: The Importance Of Measuring Blood Omega-3 Long Chain Polyunsaturated Fatty Acid Levels In Research, Renate H. M De Groot, Barbara J. Meyer

Illawarra Health and Medical Research Institute

A statement on measuring blood omega-3 long chain polyunsaturated fatty acid levels was developed and edited based on input from ISSFAL members and accepted by vote of the ISSFAL Board of Directors. Summary of Statement: Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) levels at baseline and post-intervention should be assessed and reported in future research to evaluate the efficacy of n-3 LCPUFA supplementation: b ecause; 1. there are numerous factors that affect n-3 LCPUFA levels in humans as described in the systematic literature review [1]; 2. assessing intake of n-3 LCPUFA from the diet and/or supplements is not sufficient …

Toward Personalized Synchrotron Microbeam Radiation Therapy, Elette Engels, Nan Li, Jeremy A. Davis, Jason Paino, Matthew Cameron, Andrew Dipuglia, Sarah Vogel, Michael Valceski, Abass Khochaiche, Alice O'Keefe, Micah Barnes, Ashley J. Cullen, Andrew Stevenson, Susanna Guatelli, Anatoly B. Rosenfeld, Michael L. F Lerch, Stephanie Corde, Moeava Tehei

Illawarra Health and Medical Research Institute

Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented …

Role Of Area-Level Access To Primary Care On The Geographic Variation Of Cardiometabolic Risk Factor Distribution: A Multilevel Analysis Of The Adult Residents In The Illawarra—Shoalhaven Region Of Nsw, Australia, Renin Melkias Baby Selvi Toms, Xiaoqi Feng, Darren J. Mayne, Andrew D. Bonney

Illawarra Health and Medical Research Institute

Background: Access to primary care is important for the identification, control and management of cardiometabolic risk factors (CMRFs). This study investigated whether differences in geographic access to primary care explained area-level variation in CMRFs. Methods: Multilevel logistic regression models were used to derive the association between area-level access to primary care and seven discrete CMRFs after adjusting for individual and area-level co-variates. Two-step floating catchment area method was used to calculate the geographic access to primary care for the small areas within the study region. Results: Geographic access to primary care was inversely associated with low high density lipoprotein (OR …

N-Alkylisatin-Loaded Liposomes Target The Urokinase Plasminogen Activator System In Breast Cancer, Lisa Belfiore, Darren Saunders, Marie Ranson, Kara L. Vine

Illawarra Health and Medical Research Institute

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. The urokinase plasminogen activator and its receptor (uPA/uPAR) are biomarkers for metastasis, especially in triple-negative breast cancer. We prepared anti-mitotic N-alkylisatin (N-AI)-loaded liposomes functionalized with the uPA/uPAR targeting ligand, plasminogen activator inhibitor type 2 (PAI-2/SerpinB2), and assessed liposome uptake in vitro and in vivo. Receptor-dependent uptake of PAI-2-functionalized liposomes was significantly higher in the uPA/uPAR overexpressing MDA-MB-231 breast cancer cell line relative to the low uPAR/uPAR expressing MCF-7 breast cancer cell line. Furthermore, N-AI cytotoxicity was enhanced in a receptor-dependent manner. In vivo, PAI-2 N-AI liposomes had a plasma half-life of …

A Qualitative Exploration Of Smart Recovery Meetings In Australia And The Role Of A Digital Platform To Support Routine Outcome Monitoring, Rebecca Gray, Peter James Kelly, Alison Beck, Amanda Baker, Frank P. Deane, Joanne Neale, Carla Treloar, Leanne Hides, Victoria Manning, Anthony Shakeshaft, John F. Kelly, Angela Argent, Ryan Mcglaughlin

Illawarra Health and Medical Research Institute

Previous research has reported on the benefits of mutual support groups. However, such groups do not routinely collect data on participant outcomes. Moreover, the effect of collecting outcomes measures on these groups is unknown. The objective of this mixed methods study was to elicit participant views on using a novel, purpose built digital platform for routine outcome monitoring (ROM) as a standard component of a mutual support group. SMART Recovery, or the Self-Management and Recovery Training program, is group-based and uses professional clinicians to facilitate discussion and foster mutual support for a range of addictive behaviours, alongside Cognitive Behavioural Therapy …

Novel Behavioural Characteristics Of The Superoxide Dismutase 1 G93a (Sod1G93a) Mouse Model Of Amyotrophic Lateral Sclerosis Include Sex-Dependent Phenotypes, Fabian Kreilaus, Stefan Guerra, Rebecca Masanetz, Victoria Menne, Justin J. Yerbury, Tim Karl

Illawarra Health and Medical Research Institute

Amyotrophic lateral sclerosis (ALS) involves the rapid degeneration of upper and lower motor neurons leading to weakening and paralysis of voluntary movements. Mutations in copper‐zinc superoxide dismutase 1 (SOD1) are a known genetic cause of ALS, and the SOD1 ^G93A mouse has been used extensively to investigate molecular mechanisms in ALS. In recent years, evidence suggests that ALS and frontotemporal dementia form a spectrum disorder ranging from motor to cognitive dysfunctions. Thus, we tested male and female SOD1 ^G93A mice for the first time before the onset of debilitating motor impairments in behavioural domains relevant to both ALS …

Current Practice In The Introduction Of Solid Foods For Preterm Infants, Jane Cleary, Sayne Dalton, Alexandra Harman, Ian M. R Wright

Illawarra Health and Medical Research Institute

Objective: The present study compared the age of first solid foods in a cohort of preterm infants with term infants and identified factors influencing timing of solid food introduction. Design: Structured interviews on infant feeding practices, growth and medical status at term equivalence and at 3, 6, 9 and 12 months corrected postnatal age. The age of solid food introduction was compared between term and preterm infants, and the influence of maternal, infant and milk feeding factors was assessed. Setting: This prospective longitudinal study recruited primary carers of preterm and term infants from a regional metropolitan referral hospital in eastern …

Validation And Evaluation Of The Mandarin Version Of The Oral Health Literacy Adult Questionnaire In Taiwan, Mu-Hsing Ho, Jed Montayre, H.C. Chang, Jee Young Joo, Mohammad Naghibi Sistani, Yen-Kuang Lin, Victoria Traynor, Chia-Chi Chang, Megan F. Liu

Illawarra Health and Medical Research Institute

Objectives

This study aimed to translate the Oral Health Literacy Adult Questionnaire into a Mandarin version (MOHL‐AQ) and to examine its psychometric properties.

Methods

A methodological research using psychometric testing and evaluation of a translated instrument. A convenience sample of 402 participants from northern Taiwan were recruited for the validation of the MOHL‐AQ. Internal consistency reliability, split‐half reliability, inter‐rater reliability, face validity, content validity, and construct validity were evaluated.

Results

The value of internal consistency and split‐half reliability of the MOHL‐AQ were 0.77 and 0.78, respectively. Content validity reported a high content validity index (CVI = 95%). Exploratory factor analysis …

Cognitive Distortions In Relation To Plasma Cortisol And Oxytocin Levels In Major Depressive Disorder, Susan J. Thomas, Theresa A. Larkin

Illawarra Health and Medical Research Institute

Negative thinking is prominent in major depressive disorder (MDD). Cognitive models propose that negative thinking influences the hypothalamus-pituitary-adrenal axis and cortisol release. Oxytocin is also linked to MDD, social and affective processing, and stress buffering. Little research has examined direct relationships between negative cognitions, cortisol, and oxytocin. Methods: Sixty-one unmedicated participants meeting DSM-5 criteria for MDD and 60 healthy controls completed measures of psychopathology, stress, and cognitions. Plasma samples were analyzed for cortisol and oxytocin. Between-group analyses of variance were conducted along with correlational, regression and mediation analyses. Results: Depressed participants reported greater frequency and believability of negative thoughts than …

Establishment Of Novel Long-Term Cultures From Epcam Positive And Negative Circulating Tumour Cells From Patients With Metastatic Gastroesophageal Cancer, Daniel Brungs, Elahe Minaei, Ann-Katrin Piper, Jay Perry, Ashleigh Splitt, Martin G. Carolan, Shantay Ryan, Xiao Wu, Stephanie Corde, Moeava Tehei, Morteza Aghmesheh, Kara L. Vine, Therese M. Becker, Marie Ranson

Illawarra Health and Medical Research Institute

Circulating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug sensitivity testing, and investigation of the pathobiology of metastases. We report for the first time the establishment and characterisation of two continuous CTC lines from patients with gastroesophageal cancer. The two cell lines (designated UWG01CTC and UWG02CTC) demonstrated rapid tumorigenic growth in immunodeficient mice and exhibit distinct genotypic …

Olanzapine Increases Ampk-Npy Orexigenic Signaling By Disrupting H1r-Ghsr1a Interaction In The Hypothalamic Neurons Of Mice, Xiaoqi Chen, Yinghua Yu, Peng Zheng, Tiantian Jin, Meng He, Mingxuan Zheng, Xueqin Song, Alison L. Jones, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Second generation antipsychotics, particularly olanzapine, induce severe obesity, which is associated with their antagonistic effect on the histamine H1 receptor (H1R). We have previously demonstrated that oral administration of olanzapine increases the concentration of neuropeptide Y (NPY) in the hypothalamus of rats, accompanied by hyperphagia and weight gain. However, it is unclear if the increased NPY after olanzapine administration is due to its direct effect on hypothalamic neurons and its H1R antagonistic property. In the present study, we showed that with an inverted U-shape dose-response curve, olanzapine increased NPY expression in the NPY-GFP hypothalamic neurons; however, this was not the …

Maternal Adipose Tissue Expansion, A Missing Link In The Prediction Of Birth Weight Centile, Eleanor M. Jarvie, Frances M. Stewart, Jane E. Ramsay, Elizabeth A. Brown, Barbara J. Meyer, Gunilla Olivecrona, Bruce A. Griffin, Dilys J. Freeman

Illawarra Health and Medical Research Institute

Context

Maternal body mass index (BMI) is associated with increased birth weight but does not explain all the variance in fetal adiposity. Objective

To assess the contribution of maternal body fat distribution to offspring birth weight and adiposity. Design

Longitudinal study throughout gestation and at delivery. Setting

Women recruited at 12 weeks of gestation and followed up at 26 and 36 weeks. Cord blood was collected at delivery. Patients

Pregnant women (n = 45) with BMI 18.0 to 46.3 kg/m² and healthy pregnancy outcome. Methods

Maternal first trimester abdominal subcutaneous and visceral adipose tissue thickness (SAT and VAT) was …

Increased P2x7 Expression In The Gastrointestinal Tract And Skin In A Humanised Mouse Model Of Graft-Versus-Host Disease, Peter Cuthbertson, Sam Adhikary, Nicholas Geraghty, Thomas Guy, Amirazin Hadjiashrafi, Stephen Fuller, Diane T. Ly, Debbie Watson, Ronald Sluyter

Illawarra Health and Medical Research Institute

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapy for blood cancers; but results in the development of graft-versus-host disease (GVHD) in up to 70% of recipients. During GVHD, tissue damage results in ATP release into the extracellular compartment activating P2X7 on antigen-presenting cells, leading to the release of pro-inflammatory cytokines and subsequent activation of donor T cells. Therefore, the aim of the present study was to examine murine (m) P2rx7 and human (h) P2RX7 gene expression in GVHD target organs of humanised mice, and further characterise disease impact in these organs. METHODS: NOD-scid IL2Rγnull (NSG) mice were …

Stunting Is A Recognised Problem: Evidence For The Potential Benefits Of Omega-3 Long Chain Polyunsaturated Fatty Acids, Setyaningrum Rahmawaty, Barbara J. Meyer

Illawarra Health and Medical Research Institute

Stunting remains a major nutritional problem worldwide, especially in middle and low-income countries including Indonesia. A number of nutrition feeding programs to cure stunting is basically addressing the problem of malnutrition. These programs are particularly designed to promote recovery of normal metabolic function and weight gain. The currently available remedial formula for malnutrition contains energy and nutrients to recover their weight, but there is less nutrition that would support optimal functional development of tissues including central nervous system. Research has well documented that sufficient intakes of dietary omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) are important for optimal health …

Study Protocol The Continuing Care Project: A Randomised Controlled Trial Of A Continuing Care Telephone Intervention Following Residential Substance Dependence Treatment, Peter James Kelly, Frank P. Deane, Gerard Byrne, Tayla Degan, Briony Osborne, Camilla Townsend, James Mckay, Laura Robinson, Christopher Oldmeadow, Kenny Lawson, Andrew Searles, Joanne Lunn

Illawarra Health and Medical Research Institute

Background: A priority area in the field of substance dependence treatment is reducing the rates of relapse. Previous research has demonstrated that telephone delivered continuing care interventions are both clinically and cost effective when delivered as a component of outpatient treatment. This protocol describes a NSW Health funded study that assesses the effectiveness of delivering a telephone delivered continuing care intervention for people leaving residential substance treatment in Australia. Methods/design: All participants will be attending residential alcohol and other drug treatment provided by The Salvation Army or We Help Ourselves. The study will be conducted as a randomised controlled trial, …

Tryptophan Residue 32 In Human Cu-Zn Superoxide Dismutase Modulates Prion-Like Propagation And Strain Selection, Anthony Crown, Luke Mcalary, Eric Fagerli, Hilda Brown, Justin J. Yerbury, Ahmad Galaleldeen, Neil Cashman, David Borchelt, Jacob Ayers

Illawarra Health and Medical Research Institute

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) associated with familial amyotrophic lateral sclerosis cause the protein to aggregate via a prion-like process in which soluble molecules are recruited to aggregates by conformational templating. These misfolded SOD1 proteins can propagate aggregation-inducing conformations across cellular membranes. Prior studies demonstrated that mutation of a Trp (W) residue at position 32 to Ser (S) suppresses the propagation of misfolded conformations between cells, whereas other studies have shown that mutation of Trp 32 to Phe (F), or Cys 111 to Ser, can act in cis to attenuate aggregation of mutant SOD1. By expressing mutant SOD1 …

A Practical Guide For The Use Of Very Low Calorie Diets In Adults With Chronic Kidney Disease, Kelly Lambert, Su Bahceci, Beth Lucan, Murielle Ryan

Illawarra Health and Medical Research Institute

Obesity is increasingly common in individuals with chronic kidney disease (CKD). Being overweight or obese is associated with both the development and progression of kidney disease. Lifestyle interventions such as the use of very low-calorie diets (VLCD) are being used increasingly for patients with CKD despite warnings from manufacturers that they should be avoided or used with caution. Whilst these diets are effective and can induce rapid weight loss and suppress appetite, their use in patients with chronic and end stage kidney disease is more complex than in the general population. VLCD use in adults with kidney disease requires a …

Risperidone Stimulates Food Intake And Induces Body Weight Gain Via The Hypothalamic Arcuate Nucleus 5-Ht2c Receptor—Npy Pathway, Xiao Wan, Fan Zeng, Xu-Feng Huang, He Yang, Lan Wang, Yan-Chuan Shi, Zhi Zhang, Shu Lin

Illawarra Health and Medical Research Institute

Aims

Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated.

Methods

Twenty‐four C57BL/6J mice were divided into four groups: a control group; a risperidone‐treated group; a lorcaserin‐treated group; and a combined risperidone + lorcaserin‐treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes …

Proportion Of Kindergarten Children Meeting The Who Guidelines On Physical Activity, Sedentary Behaviour And Sleep And Associations With Adiposity In Urban Beijing, Hongyan Guan, Zhiguang Zhang, Bo Wang, Anthony D. Okely, Meiling Tong, Jianxin Wu, Ting Zhang

Illawarra Health and Medical Research Institute

Background

World Health Organisation (WHO) Guidelines on Physical Activity, Sedentary Behaviour and Sleep for Children under 5 Years of Age were released in 2019. The aim of this study was to examine the proportion of Chinese kindergarten children who met each individual guideline and each combination of the guidelines and the associations with adiposity.

Methods

Participants were 254 kindergarten children aged 4.1–6.3 years recruited from three kindergartens in urban area of Beijing. Physical activity, sedentary behaviour and sleep duration were assessed using 24-h accelerometry over three consecutive days. Screen time was reported by parents. Weight and height were measured; and …