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Full-Text Articles in Medicine and Health Sciences

Alteration To Hippocampal Volume And Shape Confined To Cannabis Dependence: A Multi-Site Study [Accepted Manuscript], Yann Chye, Valentina Lorenzetti, Chao Suo, Albert Batalla, Janna Cousijn, Anna E. Goudriaan, Mark Jenkinson, Rocio Martin-Santos, Sarah Whittle, Murat Yücel, Nadia Solowij Jan 2019

Alteration To Hippocampal Volume And Shape Confined To Cannabis Dependence: A Multi-Site Study [Accepted Manuscript], Yann Chye, Valentina Lorenzetti, Chao Suo, Albert Batalla, Janna Cousijn, Anna E. Goudriaan, Mark Jenkinson, Rocio Martin-Santos, Sarah Whittle, Murat Yücel, Nadia Solowij

Faculty of Health Sciences Publications

Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non‐dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippocampus, one of the most consistently altered brain regions in cannabis users, in a large multi‐site dataset aggregated across four research sites. We compared hippocampal volume and vertex‐level hippocampal shape differences (1) between 121 non ...


Patients With Prostate Cancer And Androgen Deprivation Therapy Have Increased Risk Of Fractures—A Study From The Fractures And Fall Injuries In The Elderly Cohort (Frailco), M. Wallander, K. F. Axelsson, D. Lundh, Mattias Lorentzon Jan 2019

Patients With Prostate Cancer And Androgen Deprivation Therapy Have Increased Risk Of Fractures—A Study From The Fractures And Fall Injuries In The Elderly Cohort (Frailco), M. Wallander, K. F. Axelsson, D. Lundh, Mattias Lorentzon

Faculty of Health Sciences Publications

Summary Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures. Introduction: Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer. Methods ...


Personalized Medicine And Hospitalization For Heart Failure: If We Understand It, We May Be Successful In Treating It, Faheem A. Ahmad, Mark C. Petrie, John J. V. Mcmurray, Ninian N. Lang Jan 2019

Personalized Medicine And Hospitalization For Heart Failure: If We Understand It, We May Be Successful In Treating It, Faheem A. Ahmad, Mark C. Petrie, John J. V. Mcmurray, Ninian N. Lang

Faculty of Health Sciences Publications

Randomized trials in patients with hospitalized heart failure (HHF) continue to frustrate the cardiology community. Promising haemodynamic, structural and biomarker findings from phase 2 studies consistently fail to deliver substantive benefits in larger outcome trials. What underlies these recurrent failures? Why are persistently high readmission and post‐discharge mortality rates not being reduced? Challenging any pre‐conceived ideas about the existence of a ‘typical’ acutely decompensated heart failure patient is fundamental, as is the adoption of a carefully personalized approach. These individuals come from a remarkably heterogeneous group. Surely precise phenotyping should translate to a more successful therapeutic approach?


Effect Of Abaloparatide On Vertebral,Nonvertebral, Major Osteoporotic And Clinical Fractures In A Subset Of Postmenopausal Women At Increased Risk Of Fracture By Frax Probability, Eugene V. Mccloskey, Lorraine Fitzpatrick, M.-Y. Hu, G. Williams, John A. Kanis Jan 2019

Effect Of Abaloparatide On Vertebral,Nonvertebral, Major Osteoporotic And Clinical Fractures In A Subset Of Postmenopausal Women At Increased Risk Of Fracture By Frax Probability, Eugene V. Mccloskey, Lorraine Fitzpatrick, M.-Y. Hu, G. Williams, John A. Kanis

Faculty of Health Sciences Publications

Summary We evaluated the efficacy of abaloparatide in women who were at increased risk for fracture, based on CHMP recommended risk thresholds, at the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) study baseline. Among patients at high risk based on FRAX probabilities, 18 months of abaloparatide significantly decreased risk for all fracture endpoints compared with placebo. Purpose Abaloparatide, a novel anabolic agent for the treatment of postmenopausal osteoporosis, significantly reduced the risk of vertebral and nonvertebral fractures in the ACTIVE study compared with placebo. In this post hoc analysis, we evaluated abaloparatide’s efficacy in a subset of women in ...


Metformin Use And Cardiovascular Events In Patients With Type 2 Diabetes And Chronic Kidney Disease [Accepted Manuscript], David M. Charytan, Scott D. Solomon, Peter Ivanovich, Giuseppe Remuzzi, Mark E. Cooper, Janet B. Mcgill, Hans-Henrik Parving, Patrick Parfrey, Ajay K. Singh, Emmanuel A. Burdmann, Andrew S. Levey, Kai-Uwe Eckardt, John J. V. Mcmurray, Larry A. Weinrauch, Jiankang Liu, Brian L. Claggett, Eldrin F. Lewis, Marc A. Pfeffer Jan 2019

Metformin Use And Cardiovascular Events In Patients With Type 2 Diabetes And Chronic Kidney Disease [Accepted Manuscript], David M. Charytan, Scott D. Solomon, Peter Ivanovich, Giuseppe Remuzzi, Mark E. Cooper, Janet B. Mcgill, Hans-Henrik Parving, Patrick Parfrey, Ajay K. Singh, Emmanuel A. Burdmann, Andrew S. Levey, Kai-Uwe Eckardt, John J. V. Mcmurray, Larry A. Weinrauch, Jiankang Liu, Brian L. Claggett, Eldrin F. Lewis, Marc A. Pfeffer

Faculty of Health Sciences Publications

Aims Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. Materials and methods All‐cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non‐users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin‐alfa) Therapy (TREAT) (NCT00093015). Outcomes ...


Outcomes And Effect Of Treatment According To Etiology In Hfref: An Analysis Of Paradigm-Hf, Craig Balmforth, Joanne Simpson, Li Shen, Pardeep S. Jhund, Martin P. Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Victor C. Shi, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Milton Packer, John J. V. Mcmurray Jan 2019

Outcomes And Effect Of Treatment According To Etiology In Hfref: An Analysis Of Paradigm-Hf, Craig Balmforth, Joanne Simpson, Li Shen, Pardeep S. Jhund, Martin P. Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Victor C. Shi, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Milton Packer, John J. V. Mcmurray

Faculty of Health Sciences Publications

Objectives The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial. Background Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy. Methods We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite ...


Reduced Loop Diuretic Use In Patients Taking Sacubitril/Valsartan Compared With Enelapril: The Paradigm-Hf Trial, Orly Vardeny, Brian L. Claggett, Jessica Kachadourian, Akshay S. Desai, Milton Packer, Jean L. Rouleau, Michael R. Zile, Karl Swedberg, Martin P. Lefkowitz, Victor C. Shi, John J. V. Mcmurray, Scott D. Solomon Jan 2019

Reduced Loop Diuretic Use In Patients Taking Sacubitril/Valsartan Compared With Enelapril: The Paradigm-Hf Trial, Orly Vardeny, Brian L. Claggett, Jessica Kachadourian, Akshay S. Desai, Milton Packer, Jean L. Rouleau, Michael R. Zile, Karl Swedberg, Martin P. Lefkowitz, Victor C. Shi, John J. V. Mcmurray, Scott D. Solomon

Faculty of Health Sciences Publications

Aims To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial. Methods and results Overall, 8399 patients with New York Heart Association class II–IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide ...


Sacubitril/Valsartan In Asian Patients With Heart Failure With Reduced Ejection Fraction, Pooja Dewan, Kieran F. Docherty, John J. V. Mcmurray Jan 2019

Sacubitril/Valsartan In Asian Patients With Heart Failure With Reduced Ejection Fraction, Pooja Dewan, Kieran F. Docherty, John J. V. Mcmurray

Faculty of Health Sciences Publications

The Prospective comparison of Angiotensin Receptor-neprilysin inhibitor (ARNI) with Angiotensin converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and morbidity in Heart Failure (HF) trial (PARADIGM-HF) showed that adding a neprilysin inhibitor (sacubitril) to a renin-angiotensin system blocker (and other standard therapy) reduced morbidity and mortality in ambulatory patients with chronic HF with reduced ejection fraction (HFrEF). In PARADIGM-HF, valsartan combined with sacubitril (a so-called ARNI) was superior to the current gold standard of an ACEI, specifically enalapril, reducing the risk of the primary composite outcome of cardiovascular (CV) death or first HF hospitalization by 20% and all-cause ...


Single-Dose Prednisolone Alters Endocrine And Haematologic Responses And Exercise Performance In Men, Alexander Tacey, Lewan Parker, Bu B. Yeap, John Joseph, Ee Mun Lim, Andrew Garnham, David L. Hare, Tara C. Brennan-Speranza, Itamar Levinger Jan 2019

Single-Dose Prednisolone Alters Endocrine And Haematologic Responses And Exercise Performance In Men, Alexander Tacey, Lewan Parker, Bu B. Yeap, John Joseph, Ee Mun Lim, Andrew Garnham, David L. Hare, Tara C. Brennan-Speranza, Itamar Levinger

Faculty of Health Sciences Publications

The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood samples were taken at rest, immediately post exercise and up to ...


Statins In The Prevention And Treatment Of Heart Failure: A Review Of The Evidence, Matthew M. Y. Lee, Naveed Sattar, John J. V. Mcmurray, Chris J. Packard Jan 2019

Statins In The Prevention And Treatment Of Heart Failure: A Review Of The Evidence, Matthew M. Y. Lee, Naveed Sattar, John J. V. Mcmurray, Chris J. Packard

Faculty of Health Sciences Publications

Purpose of Review We summarize the best evidence for statins in the prevention and treatment of heart failure. Recent Findings In patients with cardiovascular risk factors or established atherosclerotic cardiovascular disease (but without heart failure), statins reduce the risk of incident heart failure—mainly by preventing myocardial infarction although an additional benefit from reducing myocardial ischemia cannot be excluded. However, in patients with established heart failure, statins do not reduce the risk of cardiovascular death, which is mainly caused by pump failure and ventricular arrhythmias. Retrospective analyses, however, suggest that statins may reduce the rate of heart failure hospitalization and ...


Prognostic Implications Of Changes In Amino-Terminal Pro–B-Type Natriuretic Peptide In Acute Decompensated Heart Failure: Insights From Ascend-Hf [Accepted Manuscript], Justin L. Grodin, Max J. Liebo, Javed Butler, Marco Metra, G. Michael Felker, Adrian F. Hernandez, Adriaan A. Voors, John J. V. Mcmurray, Paul W. Armstrong, Christopher M. O'Connor, Randall C. Starling, Richard W. Troughton, W. H. Wilson Tang Jan 2019

Prognostic Implications Of Changes In Amino-Terminal Pro–B-Type Natriuretic Peptide In Acute Decompensated Heart Failure: Insights From Ascend-Hf [Accepted Manuscript], Justin L. Grodin, Max J. Liebo, Javed Butler, Marco Metra, G. Michael Felker, Adrian F. Hernandez, Adriaan A. Voors, John J. V. Mcmurray, Paul W. Armstrong, Christopher M. O'Connor, Randall C. Starling, Richard W. Troughton, W. H. Wilson Tang

Faculty of Health Sciences Publications

Background: Amino-terminal pro–B-type natriuretic peptide (NTproBNP) is closely associated with prognosis in acute decompensated heart failure (ADHF). As a result, there has been great interest measuring it during the course of treatment. The prognostic implications in both short-term and follow-up changes in NTproBNP need further clarification. Methods: Baseline, 48–72 hour, and 30-day NTproBNP levels were measured in 795 subjects in the ASCEND-HF trial. Multivariable logistic and Cox-proportional hazards models were used to test the association between static, relative, and absolute changes in NTproBNP with outcomes during and after ADHF. Results: The median NTproBNP at baseline was 5773 (2981 ...


Decision-Making Impairment In Long Term Opiate Users, Kathryn Biernacki Mar 2018

Decision-Making Impairment In Long Term Opiate Users, Kathryn Biernacki

Theses

The overall aim of this PhD thesis was to conduct a comprehensive investigation of decision-making impairment in long term opiate users, using three studies. The first study aimed to determine the extent of the decision-making impairment and to establish whether other co-morbid factors impacted on the severity of this deficit. Using meta-analysis, the results indicated that opiate use is associated with relatively severe decision-making impairment, and that co-morbid factors, such as head injury and poly-substance dependence did not significantly change the magnitude of the impairment. Furthermore, the decision-making impairment in opiate users was not mitigated by abstinence, and the duration ...


Normal Bone Microstructure And Density But Worse Physical Function In Older Women Treated With Selective Serotonin Reuptake Inhibitors, A Cross-Sectional Population-Based Study, Berit A. M. Larsson, Dan Mellström, Lisa Johansson, Anna G. Nilsson, Mattias Lorentzon, Daniel Sundh Jan 2018

Normal Bone Microstructure And Density But Worse Physical Function In Older Women Treated With Selective Serotonin Reuptake Inhibitors, A Cross-Sectional Population-Based Study, Berit A. M. Larsson, Dan Mellström, Lisa Johansson, Anna G. Nilsson, Mattias Lorentzon, Daniel Sundh

Faculty of Health Sciences Publications

Depression in the elderly is today often treated with selective serotonin reuptake inhibitors (SSRIs) because of their favorable adverse effect profile. However, treatment with SSRIs is associated with increased risk of fractures. Whether this increased risk depends on reduced bone strength or increased fall risk due to reduced physical function is not certain. The aim was therefore to investigate if treatment with SSRIs is associated with impaired bone microstructure, bone density, or physical function in older women. From an ongoing population-based study, 1057 women (77.7 ± 1.5 years) were included. Validated questionnaires were used to assess information regarding medical ...


Onset Symptoms, Tobacco Smoking, And Progressive-Onset Phenotype Are Associated With A Delayed Onset Of Multiple Sclerosis, And Marijuana Use With An Earlier Onset, Chunrong Tao, Steve Simpson Jr, Bruce V. Taylor, Leigh Blizzard, Robyn M. Lucas, Anne-Louise Ponsonby, Simon Broadley, Auslong/Ausimmune Investigators Group, Ingrid Van Der Mei Jan 2018

Onset Symptoms, Tobacco Smoking, And Progressive-Onset Phenotype Are Associated With A Delayed Onset Of Multiple Sclerosis, And Marijuana Use With An Earlier Onset, Chunrong Tao, Steve Simpson Jr, Bruce V. Taylor, Leigh Blizzard, Robyn M. Lucas, Anne-Louise Ponsonby, Simon Broadley, Auslong/Ausimmune Investigators Group, Ingrid Van Der Mei

Faculty of Health Sciences Publications

Background: Age at symptom onset (ASO) is a prognostic factor that could affect the accrual of disability in multiple sclerosis (MS) patients. Some factors are known to influence the risk of multiple sclerosis (MS), but their influence on the ASO is less well-investigated. Objective: Examine the associations between known or emerging MS risk factors and ASO. Methods: This was a multicenter study, incident cases (n = 279) with first clinical diagnosis of demyelinating event aged 18–59 years recruited at four Australian centres (latitudes 27°-43°S), from 1 November 2003 to 31 December 2006. Environmental/behavioral variables and initial symptoms ...


Treatment Of Personality Disorder Using A Whole Of Service Stepped Care Approach: A Cluster Randomized Controlled Trial, Brin F. S. Grenyer, Kate L. Lewis, Mahnaz Fanaian, Beth Kotze Jan 2018

Treatment Of Personality Disorder Using A Whole Of Service Stepped Care Approach: A Cluster Randomized Controlled Trial, Brin F. S. Grenyer, Kate L. Lewis, Mahnaz Fanaian, Beth Kotze

Faculty of Health Sciences Publications

Background and objectives: People with personality disorders are prevalent in emergency and inpatient mental health services. We examined whether implementing a stepped care model of psychological therapy reduces demand on hospital units by people with personality disorder, in a cluster randomized controlled trial. Method: A total of 642 inpatients (average age 36.8, 50.5% female) with a primary ICD-10 personality disorder were recruited during 18 months baseline, then monitored during an 18 month active trial phase. In the active trial phase two equivalent sites were randomised to either treatment as usual (TAU), or a whole of service intervention that ...


Costs Of Potentially Inappropriate Medication Use In Residential Aged Care Facilities, S. L. Harrison, L. K. O'Donnell, R. Milte, S. M. Dyer, E. S. Gnanamanickam, C. Bradley, Enwu Liu, S. N. Hilmer, M. Crotty Jan 2018

Costs Of Potentially Inappropriate Medication Use In Residential Aged Care Facilities, S. L. Harrison, L. K. O'Donnell, R. Milte, S. M. Dyer, E. S. Gnanamanickam, C. Bradley, Enwu Liu, S. N. Hilmer, M. Crotty

Faculty of Health Sciences Publications

Background: The potential harms of some medications may outweigh their potential benefits (inappropriate medication use). Despite recommendations to avoid the use of potentially inappropriate medications (PIMs) in older adults, the prevalence of PIM use is high in different settings including residential aged care. However, it remains unclear what the costs of these medications are in this setting. The main objective of this study was to determine the costs of PIMs in older adults living in residential care. A secondary objective was to examine if there was a difference in costs of PIMs in a home-like model of residential care compared ...


Genetic Determinants Of Circulating Estrogen Levels And Evidence Of A Causal Effect Of Estradiol On Bone Density In Men, Anna L. Eriksson, John R. B. Perry, Andreas D. Coviello, Graciela E. Delgado, Luigi Ferrucci, Andrew R. Hoffman, Ilpo T. Huhtaniemi, M. Arfan Ikram, Magnus K. Karlsson, Marcus E. Kleber, Gail A. Laughlin, Yongmei Liu, Mattias Lorentzon, Kathryn L. Lunetta, Dan Mellström, Joanne M. Murabito, Anna Murray, Maria Nethander, Carrie M. Nielson, Inga Prokopenko, Stephen R. Pye, Leslie J. Raffel, Fernando Rivadeneira, Priya Srikanth, Lisette Stolk, Alexander Teumer, Thomas G. Travison, André G. Uitterlinden, Dhananjay Vaidya, Dirk Vanderschueren, Joseph M. Zmuda, Winfried März, Eric S. Orwoll, Pamela Ouyang, Liesbeth Vandenput, Frederick C. W. Wu, Frank H. De Jong, Shalender Bhasin, Douglas P. Kiel, Claes Ohlsson Jan 2018

Genetic Determinants Of Circulating Estrogen Levels And Evidence Of A Causal Effect Of Estradiol On Bone Density In Men, Anna L. Eriksson, John R. B. Perry, Andreas D. Coviello, Graciela E. Delgado, Luigi Ferrucci, Andrew R. Hoffman, Ilpo T. Huhtaniemi, M. Arfan Ikram, Magnus K. Karlsson, Marcus E. Kleber, Gail A. Laughlin, Yongmei Liu, Mattias Lorentzon, Kathryn L. Lunetta, Dan Mellström, Joanne M. Murabito, Anna Murray, Maria Nethander, Carrie M. Nielson, Inga Prokopenko, Stephen R. Pye, Leslie J. Raffel, Fernando Rivadeneira, Priya Srikanth, Lisette Stolk, Alexander Teumer, Thomas G. Travison, André G. Uitterlinden, Dhananjay Vaidya, Dirk Vanderschueren, Joseph M. Zmuda, Winfried März, Eric S. Orwoll, Pamela Ouyang, Liesbeth Vandenput, Frederick C. W. Wu, Frank H. De Jong, Shalender Bhasin, Douglas P. Kiel, Claes Ohlsson

Faculty of Health Sciences Publications

Context Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability. Objective To investigate the genetic regulation of serum E2 and E1 in men. Design, Setting, and Participants Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts. Main Outcome Measures Genetic determinants of serum E2 and E1 levels. Results Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10−8) and Xq27.3, rs5951794 (P ...


The Development Of Toad Toxins As Potential Therapeutic Agents, Ji Qi, Abu Hasanat Zulfiker, Chun Li, David Good, Ming Q. Wei Jan 2018

The Development Of Toad Toxins As Potential Therapeutic Agents, Ji Qi, Abu Hasanat Zulfiker, Chun Li, David Good, Ming Q. Wei

Faculty of Health Sciences Publications

Toxins from toads have long been known to contain rich chemicals with great pharmaceutical potential. Recent studies have shown more than 100 such chemical components, including peptides, steroids, indole alkaloids, bufogargarizanines, organic acids, and others, in the parotoid and skins gland secretions from different species of toads. In traditional Chinese medicine (TCM), processed toad toxins have been used for treating various diseases for hundreds of years. Modern studies, including both experimental and clinical trials, have also revealed the molecular mechanisms that support the development of these components into medicines for the treatment of inflammatory diseases and cancers. More recently, there ...


Autophagy And Protein Turnover Responses To Exercise-Nutrient Interactions In Human Skeletal Muscle, William J. Smiles Jun 2017

Autophagy And Protein Turnover Responses To Exercise-Nutrient Interactions In Human Skeletal Muscle, William J. Smiles

Theses

Skeletal muscle is a dynamic tissue comprising the largest protein reservoir of the human body with a rate of turnover of ~1-2% per day. Protein turnover is regulated by the coordination of intracellular systems regulating protein synthesis and breakdown that converge in a spatiotemporal manner on lysosomal organelles responsible for integrating a variety of contractile and nutritional stimuli. One such system, autophagy, which literally means to ‘self-eat,’ involves capturing of cellular material for deliver to, and disintegration by, the lysosome. The autophagic ‘cargo’ is subsequently recycled for use in synthetic reactions and thus maintenance of protein balance. As a dynamic ...


Increased Cortical Porosity Is Associated With Daily, Not Weekly, Administration Of Equivalent Doses Of Teriparatide, Roger Zebaze, Ryoko Takao-Kawabata, Yu Peng, Ali Ghasem Zadeh, Kyoko Hirano, Hiroshi Yamane, Aya Takakura, Yukihiro Isogai, Toshinori Ishizuya, Ego Seeman Jan 2017

Increased Cortical Porosity Is Associated With Daily, Not Weekly, Administration Of Equivalent Doses Of Teriparatide, Roger Zebaze, Ryoko Takao-Kawabata, Yu Peng, Ali Ghasem Zadeh, Kyoko Hirano, Hiroshi Yamane, Aya Takakura, Yukihiro Isogai, Toshinori Ishizuya, Ego Seeman

Faculty of Health Sciences Publications

Introduction: The pharmacokinetic profile of parathyroid hormone (PTH) determines its effects on bone resorption and formation. When administered intermittently, anabolic effects are favored in comparison with the continuous treatment. Among the intermittent treatment regimens, lower frequency of administration may have a lower effect on bone remodeling. We therefore hypothesized that weekly administration of teriparatide will produce less increase in intracortical remodeling and porosity than reported using daily treatment. Methods: We treated 17 female New Zealand white rabbits aged 6 months for 1 month with teriparatide [human PTH(1-34)] as follows. (i) Vehicle-treated Control (n = 4); (ii) 20 μg/kg daily ...


Effects Of Acarbose On Cardiovascular And Diabetes Outcomes In Patients With Coronary Heart Disease And Impaired Glucose Tolerance (Ace): A Randomised, Double-Blind, Placebo-Controlled Trial [Accepted Manuscript], Rury R. Holman, Ruth L. Coleman, Juliana C. N. Chan, Jean-Louis Chiasson, Huimei Feng, Junbo Ge, Hertzel C. Gerstein, Richard Gray, Yong Huo, Zhihui Lang, John J. Mcmurray, Lars Rydén, Stefan Schröder, Yihong Sun, Michael J. Theodorakis, Michal Tendera, Lynne Tucker, Jaakko Tuomilehto, Yidong Wei, Wenying Yang, Duolao Wang, Dayi Hu, Changyu Pan Jan 2017

Effects Of Acarbose On Cardiovascular And Diabetes Outcomes In Patients With Coronary Heart Disease And Impaired Glucose Tolerance (Ace): A Randomised, Double-Blind, Placebo-Controlled Trial [Accepted Manuscript], Rury R. Holman, Ruth L. Coleman, Juliana C. N. Chan, Jean-Louis Chiasson, Huimei Feng, Junbo Ge, Hertzel C. Gerstein, Richard Gray, Yong Huo, Zhihui Lang, John J. Mcmurray, Lars Rydén, Stefan Schröder, Yihong Sun, Michael J. Theodorakis, Michal Tendera, Lynne Tucker, Jaakko Tuomilehto, Yidong Wei, Wenying Yang, Duolao Wang, Dayi Hu, Changyu Pan

Faculty of Health Sciences Publications

Background: The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. Methods: The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in ...


Rewriting The Transcriptome: Adenosine-To-Inosine Rna Editing By Adars, Carl Walkley, Jin Billy Li Jan 2017

Rewriting The Transcriptome: Adenosine-To-Inosine Rna Editing By Adars, Carl Walkley, Jin Billy Li

Faculty of Health Sciences Publications

One of the most prevalent forms of post-transcritpional RNA modification is the conversion of adenosine nucleosides to inosine (A-to-I), mediated by the ADAR family of enzymes. The functional requirement and regulatory landscape for the majority of A-to-I editing events are, at present, uncertain. Recent studies have identified key in vivo functions of ADAR enzymes, informing our understanding of the biological importance of A-to-I editing. Large-scale studies have revealed how editing is regulated both in cis and in trans. This review will explore these recent studies and how they broaden our understanding of the functions and regulation of ADAR-mediated RNA editing.


Practical Issues In Evidence-Based Use Of Performance Supplements: Supplement Interactions, Repeated Use And Individual Responses, Louise M. Burke Jan 2017

Practical Issues In Evidence-Based Use Of Performance Supplements: Supplement Interactions, Repeated Use And Individual Responses, Louise M. Burke

Faculty of Health Sciences Publications

Current sports nutrition guidelines recommend that athletes only take supplements following an evidence-based analysis of their value in supporting training outcomes or competition performance in their specific event. While there is sound evidence to support the use of a few performance supplements under specific scenarios (creatine, beta-alanine, bicarbonate, caffeine, nitrate/beetroot juice and, perhaps, phosphate), there is a lack of information around several issues needed to guide the practical use of these products in competitive sport. First, there is limited knowledge around the strategy of combining the intake of several products in events in which performance benefits are seen with ...


Design, Synthesis, And Biological Activity Of 1,2,3-Triazolobenzodiazepine Bet Bromodomain Inhibitors [Accepted Manuscript], Phillip P. Sharp, Jean-Marc Garnier, Tamas Hatfaludi, Zhen Xu, David Segal, Kate E. Jarman, Hélène Jousset, Alexandra Garnham, John T. Feutrill, Anthony Cuzzupe, Peter Hall, Scott Taylor, Carl Walkley, Dean Tyler, Mark A. Dawson, Peter Czabotar, Andrew F. Wilks, Stefan Glaser, David C. S. Huang, Christopher J. Burns Jan 2017

Design, Synthesis, And Biological Activity Of 1,2,3-Triazolobenzodiazepine Bet Bromodomain Inhibitors [Accepted Manuscript], Phillip P. Sharp, Jean-Marc Garnier, Tamas Hatfaludi, Zhen Xu, David Segal, Kate E. Jarman, Hélène Jousset, Alexandra Garnham, John T. Feutrill, Anthony Cuzzupe, Peter Hall, Scott Taylor, Carl Walkley, Dean Tyler, Mark A. Dawson, Peter Czabotar, Andrew F. Wilks, Stefan Glaser, David C. S. Huang, Christopher J. Burns

Faculty of Health Sciences Publications

A number of diazepines are known to inhibit bromo- and extra-terminal domain (BET) proteins. Their BET inhibitory activity derives from the fusion of an acetyl-lysine mimetic heterocycle onto the diazepine framework. Herein we describe a straightforward, modular synthesis of novel 1,2,3-triazolobenzodiazepines and show that the 1,2,3-triazole acts as an effective acetyl-lysine mimetic heterocycle. Structure-based optimization of this series of compounds led to the development of potent BET bromodomain inhibitors with excellent activity against leukemic cells, concomitant with a reduction in c-MYC expression. These novel benzodiazepines therefore represent a promising class of therapeutic BET inhibitors.


Protein Recoding By Adar1-Mediated Rna Editing Is Not Essential For Normal Development And Homeostasis, Jacki E. Heraud-Farlow, Alistair M. Chalk, Sandra Linder, Qin Li, Scott Taylor, Joshua M. White, Lokman Pang, Brian J. Liddicoat, Ankita Gupte, Jin Billy Li, Carl Walkley Jan 2017

Protein Recoding By Adar1-Mediated Rna Editing Is Not Essential For Normal Development And Homeostasis, Jacki E. Heraud-Farlow, Alistair M. Chalk, Sandra Linder, Qin Li, Scott Taylor, Joshua M. White, Lokman Pang, Brian J. Liddicoat, Ankita Gupte, Jin Billy Li, Carl Walkley

Faculty of Health Sciences Publications

Background
Adenosine-to-inosine (A-to-I) editing of dsRNA by ADAR proteins is a pervasive epitranscriptome feature. Tens of thousands of A-to-I editing events are defined in the mouse, yet the functional impact of most is unknown. Editing causing protein recoding is the essential function of ADAR2, but an essential role for recoding by ADAR1 has not been demonstrated. ADAR1 has been proposed to have editing-dependent and editing-independent functions. The relative contribution of these in vivo has not been clearly defined. A critical function of ADAR1 is editing of endogenous RNA to prevent activation of the dsRNA sensor MDA5 (Ifih1). Outside of this ...


Individual And Combined Effects Of Cannabis And Tobacco On Drug Reward Processing In Non-Dependent Users, Chandni Hindocha, Will Lawn, Tom P. Freeman, H. Valerie Curran Jan 2017

Individual And Combined Effects Of Cannabis And Tobacco On Drug Reward Processing In Non-Dependent Users, Chandni Hindocha, Will Lawn, Tom P. Freeman, H. Valerie Curran

Faculty of Health Sciences Publications

Rationale: Cannabis and tobacco are often smoked simultaneously in joints, and this practice may increase the risks of developing tobacco and/or cannabis use disorders. Currently, there is no human experimental research on how these drugs interact on addiction-related measures. Objectives: This study aimed to investigate how cannabis and tobacco, each alone and combined together in joints, affected individuals’ demand for cannabis puffs and cigarettes, explicit liking of drug and non-drug-related stimuli and craving. Method: A double-blind, 2 (active cannabis, placebo cannabis) × 2 (active tobacco, placebo tobacco) crossover design was used with 24 non-dependent cannabis and tobacco smokers. They completed ...


Sulfonylurea Drug Pretreatment And Functional Outcome In Diabetic Patients With Acute Intracerebral Hemorrhage [Accepted Manuscript], Jason J. Chang, Yasser Khorchid, Ali Kerro, L. Goodwin Burgess, Nitin Goyal, Anne W. Alexandrov, Andrei V. Alexandrov, Georgios Tsivgoulis Jan 2017

Sulfonylurea Drug Pretreatment And Functional Outcome In Diabetic Patients With Acute Intracerebral Hemorrhage [Accepted Manuscript], Jason J. Chang, Yasser Khorchid, Ali Kerro, L. Goodwin Burgess, Nitin Goyal, Anne W. Alexandrov, Andrei V. Alexandrov, Georgios Tsivgoulis

Faculty of Health Sciences Publications

Purpose: Intracerebral hemorrhage (ICH) is associated with poor clinical outcome and high mortality. Sulfonylurea (SFU) use may be a viable therapy for inhibiting sulfonylurea receptor-1 and NCCa-ATP channels and reducing perihematomal edema and blood-brain barrierdisruption. We sought to evaluate the effects of prehospital SFU use with outcomes in diabetic patients with acute ICH. Methods: We retrospectively analyzed a cohort of diabetic patients presenting with acute ICH at a tertiary care center. Study inclusion criteria included spontaneous ICH etiology and age > 18 years. Baseline clinical severity was documented using ICH-score. Hematoma volumes (HV) on admission were calculated using ABC/2 formula ...


Psilocybin For Treatment-Resistant Depression: Fmri-Measured Brain Mechanisms, Robin L. Carhart-Harris, Leor Roseman, Mark Bolstridge, Lysia Demetriou, J. Nienke Pannekoek, Matthew B. Wall, Mark Tanner, Mendel Kaelen, John Mcgonigle, Kevin Murphy, Robert Leech, H. Valerie Curran, David J. Nutt Jan 2017

Psilocybin For Treatment-Resistant Depression: Fmri-Measured Brain Mechanisms, Robin L. Carhart-Harris, Leor Roseman, Mark Bolstridge, Lysia Demetriou, J. Nienke Pannekoek, Matthew B. Wall, Mark Tanner, Mendel Kaelen, John Mcgonigle, Kevin Murphy, Robert Leech, H. Valerie Curran, David J. Nutt

Faculty of Health Sciences Publications

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex ...


Hippocampal Harms, Protection And Recovery Following Regular Cannabis Use, Murat Yücel, Valentina Lorenzetti, C. Suo, Andrew Zalesky, Alex Fornito, Michael J. Takagi, Dan I. Lubman, Nadia Solowij Jan 2016

Hippocampal Harms, Protection And Recovery Following Regular Cannabis Use, Murat Yücel, Valentina Lorenzetti, C. Suo, Andrew Zalesky, Alex Fornito, Michael J. Takagi, Dan I. Lubman, Nadia Solowij

Faculty of Health Sciences Publications

Shifting policies towards legalisation of cannabis for therapeutic and recreational use raise significant ethical issues for health-care providers seeking evidence-based recommendations. We investigated whether heavy cannabis use is associated with persistent harms to the hippocampus, if exposure to cannabidiol offers protection, and whether recovery occurs with abstinence. To do this, we assessed 111 participants: 74 long-term regular cannabis users (with an average of 15.4 years of use) and 37 non-user healthy controls. Cannabis users included subgroups of participants who were either exposed to Δ9-tetrahydrocannabinol (THC) but not to cannabidiol (CBD) or exposed to both, and former users with sustained ...


Psilocybin With Psychological Support For Treatment-Resistant Depression: An Open-Label Feasibility Study, Robin L. Carhart-Harris, Mark Bolstridge, James Rucker, Camilla M. J. Day, David Erritzoe, Mendel Kaelen, Michael A. P. Bloomfield, James A. Rickard, Ben Forbes, Amanda Feilding, David Taylor, Steve Pilling, Valerie H. Curran, David J. Nutt Jan 2016

Psilocybin With Psychological Support For Treatment-Resistant Depression: An Open-Label Feasibility Study, Robin L. Carhart-Harris, Mark Bolstridge, James Rucker, Camilla M. J. Day, David Erritzoe, Mendel Kaelen, Michael A. P. Bloomfield, James A. Rickard, Ben Forbes, Amanda Feilding, David Taylor, Steve Pilling, Valerie H. Curran, David J. Nutt

Faculty of Health Sciences Publications

Background: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. Methods: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological ...