Chemicals and Drugs Commons^™

European Epidemiological Patterns Of Cannabis- And Substance-Related Congenital Cardiovascular Anomalies: Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, …

Quadruple Convergence – Rising Cannabis Prevalence, Intensity, Concentration And Use Disorder Treatment, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

In collating and synthesizing several data sources on cannabis exposure, Manthey and colleagues have elegantly compiled a foundational resource for subsequent epidemiological studies on cannabis use [1]. The study includes an impressive body of evidence on cannabis use prevalence (in the month and year prior to interview), high risk cannabis use (daily or near daily), tetrahydrocannabinol (THC—the principal psychoactive constituent of cannabis) concentration in European cannabis herb and processed resin (cannabis concentrates), and treatment demand for Cannabis Use Disorder (CUD). All four domains studied show a modest to dramatic increases across 2010-2019.

Cannabinoid Exposure As A Major Driver Of Pediatric Acute Lymphoid Leukaemia Rates Across The Usa: Combined Geospatial, Multiple Imputation And Causal Inference Study, Albert Stuart Reece, Gary K. Hulse

Research outputs 2014 to 2021

Background: Acute lymphoid leukaemia (ALL) is the commonest childhood cancer whose incidence is rising in many nations. In the USA, between 1975 and 2016, ALL rates (ALLRs) rose 93.51% from 1.91 to 3.70/100,000 < 20 years. ALL is more common in Caucasian-Americans than amongst minorities. The cause of both the rise and the ethnic differential is unclear, however, prenatal cannabis exposure was previously linked with elevated childhood leukaemia rates. We investigated epidemiologically if cannabis use impacted nationally on ALLRs, its ethnic effects, and if the relationship was causal. Methods: State data on overall, and ethnic ALLR from the Surveillance Epidemiology and End Results databank of the Centre for Disease Control (CDC) and National Cancer Institute (NCI) were combined with drug (cigarettes, alcoholism, cannabis, analgesics, cocaine) use data from the National Survey of Drug Use and Health; 74.1% response rate. Income and ethnicity data was from the US Census bureau. Cannabinoid concentration was from the Drug Enforcement Agency Data. Data was analyzed in R by robust and spatiotemporal regression. Results: In bivariate analyses a dose-response relationship was demonstrated between ALLR and Alcohol Use Disorder (AUD), cocaine and cannabis exposure, with the effect of cannabis being strongest (β-estimate = 3.33(95%C.I. 1.97, 4.68), P = 1.92 × 10− 6). A strong effect of cannabis use quintile on ALLR was noted (Chi.Sq. = 613.79, P = 3.04 × 10− 70). In inverse probability weighted robust regression adjusted for other substances, income and ethnicity, cannabis was independently significant (β-estimate = 4.75(0.48, 9.02), P = 0.0389). In a spatiotemporal model adjusted for all drugs, income, and ethnicity, cannabigerol exposure was significant (β-estimate = 0.26(0.01, 0.52), P = 0.0444), an effect increased by spatial lagging (THC: β-estimate = 0.47(0.12, 0.82), P = 0.0083). After missing data imputation ethnic cannabis exposure was significant (β-estimate = 0.64(0.55, 0.72), P = 3.1 × 10− 40). 33/35 minimum e-Values ranged from 1.25 to 3.94 × 1036 indicative of a causal relationship. Relaxation of cannabis legal paradigms had higher ALLR (Chi.Squ.Trend = 775.12, P = 2.14 × 10− 112). Cannabis legal states had higher ALLR (2.395 ± 0.039 v. 2.127 ± 0.008 / 100,000, P = 5.05 × 10− 10). Conclusions: Data show that ALLR is associated with cannabis consumption across space-time, is associated with the cannabinoids, THC, cannabigerol, cannabinol, cannabichromene, and cannabidiol, contributes to ethnic differentials, demonstrates prominent quintile effects, satisfies criteria for causality and is exacerbated by cannabis legalization.

Identification And Characterisation Of Putative Drug Binding Sites In Human Atp-Binding Cassette B5 (Abcb5) Transporter, Lokeswari P. Tangella, Mahreen Arooj, Evelyne Deplazes, Elin S. Gray, Ricardo L. Mancera

Research outputs 2014 to 2021

© 2020 The Author(s) The human ATP-binding cassette B5 (ABCB5) transporter, a member of the ABC transporter superfamily, is linked to chemoresistance in tumour cells by drug effluxion. However, little is known about its structure and drug-binding sites. In this study, we generated an atomistic model of the full-length human ABCB5 transporter with the highest quality using the X-ray crystal structure of mouse ABCB1 (Pgp1), a close homologue of ABCB5 and a well-studied member of the ABC family. Molecular dynamics simulations were used to validate the atomistic model of ABCB5 and characterise its structural properties in model cell membranes. Molecular …

Positive Drug Stories: Possibilities For Agency And Positive Subjectivity For Harm Reduction, Liam B. Engel, Stephen J. Bright, Monica J. Barratt, Matthew M. Allen

Research outputs 2014 to 2021

People who use drugs understand drugs and drug use in ways that are often different to the way knowledge of drug use is constructed within the dominant medico-legal discourse. Their experiences are, more often than not, represented in negative ways within dominant discourse, a disconnect that can create adverse consequences for people who use drugs, through the production of stigma and shame leading to poor health and social outcomes. A key difference in how drugs are understood by people who use drugs is the capacity of the former to recognize positive aspects of drug use and create more agentic subjectivities …

Effect Of Goji Berry On The Formation Of Extracellular Senile Plaques Of Alzheimer's Disease, Warnakulasuriya M. A. D. B. Fernando, Ke Dong, Rosalie Durham, Regine Stockmann, Vijay Jayasena

Research outputs 2014 to 2021

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and a major source of morbidity and mortality. Currently, no therapy nor drug can cure or modify AD progression, but recent studies suggest that nutritional compounds in certain foods can delay or prevent the onset of AD. Diets with high antioxidants is one of the examples which is believed to influence AD pathogenesis through direct effect on amyloid beta levels. Compared to other fruits and vegetables, goji berry (GB) has high levels of polyphenolic substances with antioxidant activities which have shown some positive effects on cognitive function while its mechanism …

Causal Inference Multiple Imputation Investigation Of The Impact Of Cannabinoids And Other Substances On Ethnic Differentials In Us Testicular Cancer Incidence, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

Background: Ethnic differences in testicular cancer rates (TCRs) are recognized internationally. Cannabis is a known risk factor for testicular cancer (TC) in multiple studies with dose-response effects demonstrated, however the interaction between ancestral and environmental mutagenic effects has not been characterized. We examined the effects of this presumed gene-environment interaction across US states. Methods: State based TCR was downloaded from the Surveillance Epidemiology and End Results (SEER) website via SEERStat. Drug use data for cigarettes, alcohol use disorder, analgesics, cannabis and cocaine was taken from the National Survey of Drug Use and Health a nationally representative study conducted annually by …

Reply To Lipworth Et Al., Angela M. Moran, Sanjay Ramakrishnan, Catherine A. Borg, Clare M. Connolly, Simon Couillard, Christine M. Mwasuku, Ian D. Pavord, Timothy S.C. Hinks, Lauri Lehtimӓki

Research outputs 2014 to 2021

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that …

Contemporary Epidemiology Of Rising Atrial Septal Defect Trends Across Usa 1991–2016: A Combined Ecological Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure. Objectives / Hypotheses. Is cannabis associated with ASDI in USA? Is this relationship causal? Methods: Geospatiotemporal cohort study, 1991–2016. Census populations of adults, babies, congenital anomalies, income and ethnicity. Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse …

Evaluation Of A Remote Symptom Assessment And Management (Sam) System For People Receiving Adjuvant Chemotherapy For Breast Or Colorectal Cancer: Mixed Methods Study, Lisa Whitehead, Laura Emery, Deborah Kirk, Diane Twigg, Deborah Brown, Joanna Dewar

Research outputs 2014 to 2021

©Lisa Whitehead, Laura Emery, Deborah Kirk, Diane Twigg, Deborah Brown, Joanna Dewar. Background: The Symptom Assessment and Management (SAM) program is a structured, online, nurse-supported intervention to support symptom self-management in people receiving adjuvant chemotherapy post surgery for breast or colorectal cancer. Objective: The objective of this study was to describe the development, implementation strategy, and evaluation of the SAM system. Methods: The development of the SAM program involved 3 phases. In phase 1, the web app was developed through consultation with consumers and clinicians and of the literature to ensure that the system was evidence-based and reflected the realities …

Characterisation Of The Structure And Oligomerisation Of Islet Amyloid Polypeptides (Iapp): A Review Of Molecular Dynamics Simulation Studies, Sandra J Moore, Krushna Sonar, Prashant Bharadwaj, Evelyne Deplazes, Ricardo L Mancera

Research outputs 2014 to 2021

Human islet amyloid polypeptide (hIAPP) is a naturally occurring, intrinsically disordered protein whose abnormal aggregation into amyloid fibrils is a pathological feature in type 2 diabetes, and its cross-aggregation with amyloid beta has been linked to an increased risk of Alzheimer's disease. The soluble, oligomeric forms of hIAPP are the most toxic to β-cells in the pancreas. However, the structure of these oligomeric forms is difficult to characterise because of their intrinsic disorder and their tendency to rapidly aggregate into insoluble fibrils. Experimental studies of hIAPP have generally used non-physiological conditions to prevent aggregation, and they have been unable to …

Hepatitis B Vaccination Coverage Among Health-Care Workers In Africa: A Systematic Review And Meta-Analysis, Asa Auta, Emmanuel O. Adewuyi, Gbednet T. Kureh, Nguavese Onoviran, Davies Adeloye

Research outputs 2014 to 2021

Objective To estimate full hepatitis B vaccination coverage (uptake of ≥ 3 doses of vaccine) among health-care workers (HCWs) in Africa. Methods We systematically searched the PubMed®, Embase®, CINAHL and Psych-Info databases for studies published from January 2010 to October 2017 that reported full hepatitis B vaccination coverage among HCWs in Africa. A random effects meta-analysis was conducted to determine pooled estimates of full vaccination coverage. Results Of the 331 articles identified, 35 studies from 15 African countries met the inclusion criteria and were included in the review. The estimated full hepatitis B vaccination coverage was 24.7% (95% CI: 17.3–32.0). …

What Are The Characteristics Of Vitamin D Metabolism In Opioid Dependence? An Exploratory Longitudinal Study In Australian Primary Care, Albert Stuart Reece, Gary Hulse

Research outputs 2014 to 2021

OBJECTIVE: Compare vitamin D levels in opioid dependence and control population and adjust for relevant confounding effects. Nuclear hormone receptors (including the vitamin D receptor) have been shown to be key transducers and regulators of intracellular metabolism and comprise an important site of pathophysiological immune and metabolic dysregulation potentially contributing towards pro-ageing changes observed in opioid-dependent patients (ODPs).

DESIGN: Longitudinal prospective comparing ODPs with general medical controls (GMCs).

SETTING: Primary care.

PARTICIPANTS: Prospective review comparing 1168 ODP (72.5% men) and 415 GMC (51.6% men, p

INTERVENTIONS: Nil. Observational study only.

PRIMARY AND SECONDARY OUTCOMES: Serum vitamin D levels and relevant …

The Effects Of Testosterone Supplementation On Cognitive Functioning In Older Men, Eka Wahjoepramono, Prita Asih, Vilia Aniwiyanti, Kevin Taddei, Satvinder Dhaliwal, Stephanie Fuller, Jonathan Foster, Malcolm Carruthers, Giuseppe Verdile, Hamid R. Sohrabi, Ralph Martins

Research outputs 2014 to 2021

Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer’s disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 …

Evolution Of Testosterone Treatment Over 25 Years: Symptom Responses, Endocrine Profiles And Cardiovascular Changes, Malcolm Carruthers, Paul Cathcart, Mark R. Feneley

Research outputs 2014 to 2021

Introduction: Testosterone treatment has evolved rapidly over the past 25 years as new, more effective and convenient methods have become available. This study reports experience with seven different methods, introduced on the market in the UK. Aim: To establish the symptom response when testosterone treatment was initiated on the basis of clinical features and symptoms of androgen deficiency, and the resulting endocrine, biochemical and physiological responses. Methods: Of 2693 patients attending the 3 Men’s Health Centers – The UK Androgen Study (UKAS), 2247 were treated. Treatments included pellet implants, oral testosterone undecanoate (Testocaps), mesterolone (Proviron), testosterone gel (Testogel), testosterone scrotal …

Identification Of Plasma Lipid Biomarkers In Alzheimer's Disease, Rhona Creegan

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the commonest form of dementia, is a chronic, progressive neurodegenerative disease which manifests clinically as a slow global decline in cognitive function, including deterioration of memory, reasoning, abstraction, language and emotional stability, culminating in a patient with end-stage disease, totally dependent on custodial care. With an ageing population, there is predicted to be a marked increase in the number of people diagnosed with AD in the coming decades, making this a significant challenge to socio-economic policy and aged care. Currently there is no cure for AD and while current therapies may temporarily ameliorate symptoms, death usually occurs …

Multiplex Biomarkers In Blood, Veer Bala Bala Gupta, Ramani Sundaram, Ralph N. Martins

Research outputs 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate …

Inhibition Of Protein Translocation At The Endoplasmic Reticulum Promotes Activation Of The Unfolded Protein Response, Craig Mckibbin, Alina Mares, Michela Piacenti, Helen Williams, Peristera Roboti, Marjo Puumalainen, Anna Callan, Karolina Lesiak-Mieczkowska, Stig Linder, Hanna Harant, Stephen High, Sabine Flitsch, Roger Whitehead, Eileithyia Swanton

Research outputs 2012

Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ESI causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel …

Finite Element Analysis Of Stress Distribution Within Metal-On-Metal Joint Replacements, Yujing Liu

Theses: Doctorates and Masters

Demand for joint replacements is rising in Australia, driven by a sharp increase in the number of joint problems associated with population aging and obesity. In artificial joints, delamination or failure within the coatings occurs when the stress reaches a critical level, resulting in large wear debris particles appearing on the contact surface between the head and the cup. The process has been described as due to a stress-corrosion-cracking mechanism. Under the same loading, stress increases when the contact area decreases, which happens in the vicinity of wear debris. As such, once wear debris is generated, a catastrophic process could …