Screening, referral and treatment of depression by Australian cardiologists
- Authors: Hare, David , Stewart, Andrew , Driscoll, Andrea , Mathews, Stephanie , Toukhsati, Samia
- Date: 2020
- Type: Text , Journal article
- Relation: Heart Lung and Circulation Vol. 29, no. 3 (2020), p. 401-404
- Full Text: false
- Reviewed:
- Description: Background: Depression is common in cardiovascular disease (CVD). Clinical practice guidelines recommend routine depression screening by cardiologists. The aim of the study was to undertake a national survey of Australian cardiologists’ clinical practice behaviours in relation to depression screening, referral, and treatment. Methods: The Cardiovascular Disease and Depression Questionnaire was sent to 827 eligible cardiologist members of Cardiac Society of Australia and New Zealand, of which a total of 524 were returned (63%). Results: Most Australian cardiologists do not routinely ask their patients about depression and only 3% routinely use depression screening instruments. Most cardiologists (>70%) think that General Practitioners (Primary Care Physicians) are primarily responsible for identifying and treating depression in CVD. Cardiologists, who understand the prognostic risks of depression in CVD and feel confident to identify and treat depression, were more likely to screen, refer and/or treat patients for depression. Conclusions: Australian cardiologists rarely use validated depression screening measures. Several brief instruments are available for use and can be easily integrated into routine patient care without taking additional consultation time. © 2019
- Description: This work was supported by the Beyond Blue Victorian Centre of Excellence in Depression and Anxiety. Prof Andrea Driscoll was supported by a Heart Foundation Future Leader fellowship 100472 from the National Heart Foundation of Australia.
Neural suppression of miRNA-181a in the kidney elevates renin expression and exacerbates hypertension in Schlager mice
- Authors: Jackson, Kristy , Gueguen, Cindy , Lim, Kyungjoon , Eikelis, Nina , Stevenson, Emily , Charchar, Fadi , Lambert, Gavin , Burke, Sandra , Paterson, Madeleine , Marques, Francine , Head, Geoffrey
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Research Vol. 43, no. 11 (2020), p. 1152-1164
- Full Text: false
- Reviewed:
- Description: BPH/2J mice are a genetic model of hypertension with overactivity of the sympathetic nervous system (SNS) and renin–angiotensin system (RAS). BPH/2J display higher renal renin mRNA and low levels of its negative regulator microRNA-181a (miR-181a). We hypothesise that high renal SNS activity may reduce miR-181a expression, which contributes to elevated RAS activity and hypertension in BPH/2J. Our aim was to determine whether in vivo administration of a renal-specific miR-181a mimic or whether renal denervation could increase renal miR-181a abundance to reduce renal renin mRNA, RAS activity and hypertension in BPH/2J mice. Blood pressure (BP) in BPH/2J and normotensive BPN/3J mice was measured via radiotelemetry probes. Mice were administered miR-181a mimic or a negative control (1–25 nmol, i.v., n = 6–10) with BP measured for 48 h after each dose or they underwent renal denervation or sham surgery (n = 7–9). Injection of 5–25 nmol miR-181a mimic reduced BP in BPH/2J mice after 36–48 h (−5.3 ± 1.8, −6.1 ± 1.9 mmHg, respectively, P < 0.016). Treatment resulted in lower renal renin and inflammatory marker (TLR4) mRNA levels in BPH/2J. The mimic abolished the hypotensive effect of blocking the RAS with enalaprilat (P < 0.01). No differences between mimic or vehicle were observed in BPN/3J mice except for a higher level of renal angiotensinogen in the mimic-treated mice. Renal miR-181a levels that were lower in sham BPH/2J mice were greater following renal denervation and were thus similar to those of BPN/3J. Our findings suggest that the reduced renal miR-181a may partially contribute to the elevated BP in BPH/2J mice, through an interaction between the renal sympathetic nerves and miR-181a regulation of the RAS. © 2020, The Japanese Society of Hypertension.
- Description: This work was supported by a grant from the National Health & Medical Research Council of Australia (NHMRC, Project grant 1065714) and in part by the Victorian Government’s OIS Program. Investigators were supported by NHMRC/National Heart Foundation (NHF) Postdoctoral Fellowships (NHMRC APP1091688 to KLJ, NHMRC APP1052659 and NHF PF12M6785 and 101185 to FZM) and NHMRC Research Fellowships (APP1042492 to GWL and APP1002186 to GAH).
Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia
- Authors: Rosenberg, Philip , Alter, Blanche , Link, Daniel , Stein, Steven , Rodger, Elin , Bolyard, Audrey , Aprikyan, Andrew , Bonilla, Mary Ann , Dror, Yigal , Kannourakis, George , Newburger, Peter , Boxer, Laurence , Dale, David
- Date: 2008
- Type: Text , Journal article
- Relation: British Journal of Haematology Vol. 140, no. 2 (2008), p. 210-213
- Full Text: false
- Reviewed:
- Description: Severe congenital neutropenia (SCN) is a heterogeneous bone marrow failure syndrome predisposing to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We studied 82 North American and Australian SCN patients enrolled in the Severe Chronic Neutropenia International Registry who were on long-term treatment with granulocyte colony-stimulating factor and for whom the neutrophil elastase (ELA2) gene was sequenced. There was no significant difference in the risk of MDS/AML in patients with mutant versus wild-type ELA2: the respective cumulative incidences at 15 years were 36% and 25% (P = 0.96). Patients with either mutant or wild-type ELA2 should be followed closely for leukaemic transformation.
- Description: C1
Short and long term mortality rates after a lower limb amputation
- Authors: Fortington, Lauren , Geertzen, Jan , Van Netten, Jaap , Postema, Klaas , Rommers, Gerardus , Dijkstra, Pieter
- Date: 2013
- Type: Text , Journal article
- Relation: European Journal of Vascular and Endovascular Surgery Vol. 46, no. 1 (July 2013), p. 124-131
- Full Text: false
- Reviewed:
- Description: Objective: To determine mortality rates after a first lower limb amputation and explore the rates for different subpopulations. Methods: Retrospective cohort study of all people who underwent a first amputation at or proximal to transtibial level, in an area of 1.7 million people. Analysis with Kaplan-Meier curves and Log Rank tests for univariate associations of psycho-social and health variables. Logistic regression for odds of death at 30-days, 1-year and 5-years. Results: 299 people were included. Median time to death was 20.3 months (95%CI: 13.1; 27.5). 30-day mortality = 22%; odds of death 2.3 times higher in people with history of cerebrovascular disease (95%CI: 1.2; 4.7, P = 0.016). 1 year mortality = 44%; odds of death 3.5 times higher for people with renal disease (95%CI: 1.8; 7.0, P < 0.001). 5-years mortality = 77%; odds of death 5.4 times higher for people with renal disease (95%CI: 1.8; 16.0,P = 0.003). Variation in mortality rates was most apparent in different age groups; people 75-84 years having better short term outcomes than those younger and older. Conclusions: Mortality rates demonstrated the frailty of this population, with almost one quarter of people dying within 30-days, and almost half at 1 year. People with cerebrovascular had higher odds of death at 30 days, and those with renal disease and 1 and 5 years, respectively.
- Description: C1
Male-specific region of the y chromosome and cardiovascular risk phylogenetic analysis and gene expression studies
- Authors: Bloomer, Lisa , Nelson, Christopher , Eales, James , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Moore, Jasbir , Consortium, Cardiogenics , Zukowska-Szczechowska, Ewa , Goodall, Alison , Thompson, John , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2013
- Type: Text , Journal article
- Relation: Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 33, no. 7 (2013), p. 1722-1727
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Objective-Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the malespecific region may explain this association. Approach and Results-A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had 0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene (UTY) and protein kinase, Y-linked, pseudogene (PRKY) in macrophages (P=0.0001 and P=0.002, respectively). Conclusions-Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors. © 2013 American Heart Association, Inc.
- Description: 2003011132
Genetic mechanisms of vascular and renal damage
- Authors: Marques, Francine , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2013
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 31, no. 11 (2013), p. 2128-2129
- Full Text: false
- Reviewed:
- Description: Document type (note)
- Description: C4
Glycogen storage disease
- Authors: Kannourakis, George
- Date: 2002
- Type: Text , Journal article
- Relation: Seminars in Hematology Vol. 39, no. 2 (2002), p. 103-106
- Full Text: false
- Reviewed:
- Description: Glycogen storage disease (GSD) is a rare autosomal-recessive disorder characterized by hypoglycemia, hepatosplenomegaly, seizures, and failure to thrive in infants. Neutropenia and/or neutrophil dysfunction develops in GSD1b, but not in other types. GSD1b results from a deficiency of the glucose-6-phosphate translocase enzyme and the genetic defect maps to chromosome 11q23. Patients with GSD1b are susceptible to recurrent bacterial infections, commonly involving the perirectal area, ears, skin, and urinary tract, although life-threatening infections, such as septicemia, pneumonia, and meningitis occur less frequently. Although the exact mechanism of neutropenia in patients with GSD1b is not known, treatment with recombinant human granulocyte colony-stimulating factor (G-CSF) has reduced the incidence of infections and has improved the quality of life of these patients. Defects in neutrophil chemotaxis and intracellular bacterial killing have been described and appear to be corrected by the use of G-CSF. To date, no cases of myelodysplasia or acute myeloid leukemia have been observed in patients with GSD1b treated with G-CSF. A significant complication of cytokine therapy is the development of hypersplenism, requiring either a reduction in the dosage of G-CSF or splenectomy. Copyright 2002, Elsevier Science (USA). All rights reserved.
Severe chronic neutropenia : Treatment and follow-up of patients in the severe chronic neutropenia international registry
- Authors: Dale, David , Cottle, Tammy , Fier, Carol , Bolyard, Audrey , Bonilla, Mary Ann , Boxer, Laurence , Cham, Bonnie , Freedman, Melvin , Kannourakis, George , Kinsey, Sally , Davis, Robert , Scarlata, Debra , Schwinzer, Beate , Zeidler, Cornelia , Welte, Karl
- Date: 2003
- Type: Text , Journal article
- Relation: American Journal of Hematology Vol. 72, no. 2 (Feb 2003), p. 82-93
- Full Text: false
- Reviewed:
- Description: Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than 0.5 x 10(9)/L, lasting for months or years. Congenital, cyclic, and idiopathic neutropenia are principal categories of SCN. Since 1994, the Severe Chronic Neutropenia International Registry (SCNIR) has collected data to monitor the clinical course, treatments, and disease outcomes for SCN patients. This report summarizes data for 853 patients, almost all treated with daily or alternate-day recombinant human granulocyte colony-stimulating factor (G-CSF or Filgrastim). G-CSF treatment increased the ANC overall from 0.34 x 10(9)/L +/- 0.018 pre-treatment to 3.70 x 10(9)/L +/- 0.18 during the first year of treatment. For most patients, the responses were durable with patients remaining on the same dose of G-CSF for many years. Long-term hematological observations showed stable mean leukocyte and neutrophil counts and gradually increasing hemoglobin levels. Thrombocytopenia developed in 4% of patients. As of January 1, 2000, myelodysplasia (MDS) or. acute myelogenous leukemia (AML) has occurred in 35 of 387 patients with congenital neutropenia with a cumulative risk of 13% after 8 years of G-CSF treatment. This event occurred without a predictable relationship to the duration or dose of G-CSF treatment. No patients with cyclic or idiopathic neutropenia developed MDS or AML. Other important adverse events included hepatomegaly, osteoporosis, vasculitis, glomerulonephritis, and deaths in 4 of 14 cases requiring splenectomy. Growth and development and the outcome of pregnancy appeared to be unaffected by G-CSF treatment. These data indicate that congenital, cyclic, and idiopathic neutropenia can be effectively treated with long-term GCSF. The risk of leukemia, osteoporosis, other potentially adverse events, and pregnancy outcome need to be further evaluated with continuing long-term observations. (C) 2003 Wiley-Liss, Inc.
- Description: C1
Out & Online effectiveness of a tailored online multi-symptom mental health and wellbeing program for same-sex attracted young adults: Study protocol for a randomised controlled trial
- Authors: Abbott, Jo-Anne , Klein, Britt , McLaren, Suzanne , Austin, David , Molloy, Mari , Meyer, Denny , McLeod, Bronte
- Date: 2014
- Type: Text , Journal article
- Relation: Trials Vol. 15, no. 1 (2014), p. 1-19
- Full Text:
- Reviewed:
- Description: Background: Same-sex attracted young adults have been found to experience higher rates of mental health problems and greater difficulties in accessing specialist mental health care services compared to their heterosexual peers. Internet-based mental health interventions have the potential to be more engaging and accessible to young adults compared to those delivered face-to-face. However, they are rarely inclusive of lesbian women and gay men. Thus, the current study aims to evaluate the effectiveness of an online mental health and wellbeing program, Out & Online (http://www.outandonline.org.au), in comparison to a wait-list control group, for reducing anxiety and depressive symptoms in same-sex attracted young adults aged between 18 and 25 years. Methods/Design: We are recruiting, through media and community organisations, 200 same-sex attracted young adults with anxiety and/or depressive symptoms and mild to moderate psychological distress (Kessler-10 score between 16 to 21). Participants will be randomly allocated to the intervention (the online program) or the wait-list control group based on a permuted blocked randomisation method to allow for stratification by gender. Participants in the intervention group will receive a tailored program for up to three types of mental health difficulties simultaneously. The primary outcome of anxiety and/or depressive symptoms, and secondary outcomes related to psychological distress, wellbeing and health behaviour will be measured at pre-intervention (0 week), post-intervention (8 weeks) and at a 3-month follow-up (20 weeks). Discussion: This online mental health and wellbeing program will be one of the first online interventions to be designed specifically to be relevant for same-sex attracted individuals. If the program is found to be effective it will improve access to specialist same-sex attracted-relevant mental health services for young adults and will facilitate wellbeing outcomes for these individuals. This program will also be a significant development in the delivery of tailored interventions that target multiple types of mental health conditions simultaneously. © 2014 Abbott et al.
A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice
- Authors: Jackson, Kristy , Marques, Francine , Watson, Anna , Palma-Rigo, Keisia , Nguyen-Huu, Thu-Phuc , Morris, Brian , Charchar, Fadi , Davern, Pamela , Head, Geoffrey
- Date: 2013
- Type: Text , Journal article
- Relation: Hypertension Vol. 62 , no. 4 (2013), p. 775-781
- Full Text: false
- Reviewed:
- Description: Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.
Leading the change: Second International Society of Hypertension New Investigators' Symposium
- Authors: Veerabhadrappa, Praveen , Charchar, Fadi , Burger, Dylan , Tomaszewski, Maciej , Carlberg, Bo
- Date: 2013
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 31, no. 2 (February 2013), p. 429-430
- Full Text: false
- Reviewed:
Meta-analysis of genome-wide gene expression differences in onset and maintenance phases of genetic hypertension
- Authors: Marques, Francine , Campain, Anna , Yang, Yee , Morris, Brian
- Date: 2010
- Type: Text , Journal article
- Relation: Hypertension Vol. 56, no. 2 (August 2010), p. 319-324
- Full Text: false
- Reviewed:
- Description: Gene expression differences accompany both the onset and established phases of hypertension. By an integrated genome-transcriptome approach we performed a meta-analysis of data from 74 microarray experiments available on public databases to identify genes with altered expression in the kidney, adrenal, heart, and artery of spontaneously hypertensive and Lyon hypertensive rats. To identify genes responsible for the onset of hypertension we used a statistical approach that sought to eliminate expression differences that occur during maturation unrelated to hypertension. Based on this adjusted fold-difference statistic, we found 36 genes for which the expression differed between the prehypertensive phase and established hypertension. Genes having possible relevance to hypertension onset included Actn2, Ankrd1, ApoE, Cd36, Csrp3, Me1, Myl3, Nppa, Nppb, Pln, Postn, Spp1, Slc21a4, Slc22a2, Thbs4, and Tnni3. In established hypertension 102 genes exhibited altered expression after Bonferroni correction (P<0.05). These included Atp5o, Ech1, Fabp3, Gnb3, Ldhb, Myh6, Lpl, Pkkaca, Vegfb, Vcam1, and reduced nicotinamide-adenine dinucleotide dehydrogenases. Among the genes identified, there was an overrepresentation of gene ontology terms involved in energy production, fatty acid and lipid metabolism, oxidation, and transport. These could contribute to increases in reactive oxygen species. Our meta-analysis has revealed many new genes for which the expression is altered in hypertension, so pointing to novel potential causative, maintenance, and responsive mechanisms and pathways.
- Description: C1
121 Telomere attrition is attenuated in ultra-marathon runners
- Authors: Denham, Joshua , Nankervis, Scott , Debiec, Radek , Harvey, Jack , Pascoe, Deborah , Marques, Francine , O’Brien, Brendan , Zukowska-Szczechowska, Ewa , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 30, no. e-Supplement (September 2012), p. e37
- Full Text: false
- Reviewed:
- Description: Background: Leukocyte telomere length is a marker of biological ageing and its shortening is associated with cardiovascular disease. Engagement in regular moderate-intensity physical activity is a recognised method of cardiovascular disease prevention. However, it is not clear whether repeated exposure to ultra-strenuous physical exercise is beneficial long-term and whether it may attenuate biological ageing. Methods: We compared leukocyte telomere length in context of inflammation and endothelial dysfunction between 67 male ultra-marathon runners and 67 age-, sex- and BMI-matched apparently healthy controls. Genomic DNA was extracted from peripheral blood and leukocyte telomere length was measured by quantitative polymerase chain reaction assays. Adhesion molecules (sICAM-1, sE-selectin) and inflammatory markers (IL-6, C-reactive protein) concentrations were measured in 67 ultra-marathon runners by quantitative sandwich enzyme immunoassay technique, high-sensitive immunoassay and ultra-sensitive double antibody sandwich ELISA, respectively. Results: Adjusted (for age, BMI, blood pressure and lipids) leukocyte telomere length was approximately 13.8% greater in the ultra-marathon runners than in the controls (P<0.001). This translates into approximately 32.9 years difference in age-related telomere length attrition. There was a strong negative linear correlation between sICAM-1 and leukocyte telomere length in the ultra-marathon runners (r=-0.33; P=0.007) and this association retained its statistical significance after adjustment for age, BMI, blood pressure and lipids in multiple regression (P=0.026). Conclusion: Prolonged, intense physical exercise may attenuate cellular ageing possibly through a protective effect on endothelial function.
- Description: C1
Meaningful and effective consultation and the construction industry of Victoria, Australia
- Authors: Ayers, Gerard , Culvenor, John , Sillitoe, Jim , Else, Dennis
- Date: 2013
- Type: Text , Journal article
- Relation: Construction Management and Economics Vol. 31, no. 6 (2013), p. 542-567
- Full Text: false
- Reviewed:
- Description: Consultation between employers and employees is mandated under Australian occupational health and safety legislation. For consultation to be considered meaningful and effective, it is generally accepted that moral and ethical principles such as trust, honesty, commitment and respect need to be recognized and applied by individuals during consultation. It is also considered that an organization's level of cultural maturity is an important element in the ability of individuals to freely engage in meaningful and effective consultation. If the value of consultation is best reflected in the degree of input and control that workers have regarding the very decisions that affect them, and if the level of worker involvement is a reflection of an organization's level of cultural maturity, it is debateable whether the notion of applying moral and ethical principles during consultation, and the adoption of the paradigm of organizational and cultural maturity, have been successfully developed and embraced in the commercial and industrial sector of the construction industry of Victoria, Australia. © 2013 Taylor and Francis Group, LLC.
- Description: C1
A phase II trial for the efficacy of physiotherapy intervention for early-onset hip osteoarthritis: Study protocol for a randomised controlled trial
- Authors: Kemp, Joanne , Moore, Kate , Fransen, Marlene , Russell, Trevor , Crossley, Kay
- Date: 2015
- Type: Text , Journal article
- Relation: Trials Vol. 16, no. 1 (2015), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: Early-onset hip osteoarthritis is commonly seen in people undergoing hip arthroscopy and is associated with increased pain, reduced ability to participate in physical activity, reduced quality of life and reduced range of motion and muscle strength. Despite this, the efficacy of non-surgical interventions such as exercise therapies remains unknown. The primary aim is to establish the feasibility of a phase III randomised controlled trial investigating a targeted physiotherapy intervention for people with early-onset hip osteoarthritis. The secondary aims are to determine the size of treatment effects of a physiotherapy intervention, targeted to improve hip joint range and hip-related symptoms in early-onset hip osteoarthritis following hip arthroscopy, compared to a health-education control. Methods: This protocol describes a randomised, assessor- and participant-blind, controlled clinical trial. We will include 20 participants who are (i) aged between 18 and 50 years; (ii) have undergone hip arthroscopy during the past six to 12 months; (iii) have early-onset hip osteoarthritis (defined as chondrolabral pathology) at the time of hip arthroscopy; and (iv) experience hip-related pain during activities. Primary outcome will be the feasibility of a phase III clinical trial. Secondary outcomes will be (i) perceived global change score; (ii) hip-related symptoms (measured using the Hip disability and Osteoarthritis Outcome Score (HOOS) pain subscale, activity subscale, and sport and recreation subscale); (iii) hip quality of life (measured using the HOOS quality of life subscale and International Hip Outcome tool; (iv) hip muscle strength and (v) hip range of motion. The physiotherapy intervention is semi-standardised, including joint and soft tissue mobilisation and stretching, hip and trunk muscle retraining and functional and activity-specific retraining and education. The control intervention encompasses individualised health education, with the same frequency and duration as the intervention. The trial primary end-point is the conclusion of the 12-week intervention, and follow-up measures will be collected at the 12-week post-baseline assessment. Discussion: The findings of this study will provide guidance regarding the feasibility of a full-scale phase III randomised controlled trial, prior to its undertaking. Trial registration: The trial protocol was registered with the Australian Clinical Trials Registry (number: 12614000426684) on 17 April 2014. © Kemp et al.
Abnormal microRNA expression in cardiac hypertrophy and the regulation of the Endog gene
- Authors: Quarrell, Sean , Marques, Francine , Jayaswal, Vivek , Curl, Claire , Nankervis, Scott , Yang, Jean , Delbridge, Lea , Harrap, Stephen , Charchar, Fadi
- Date: 2012
- Type: Text , Journal article
- Relation: Heart, Lung and Circulation Vol. 21, no. Supplement 1 (2012), p. s7
- Full Text: false
- Reviewed:
- Description: A deficiency in the gene for endonuclease G (Endog) was recently described as a genetic determinant of cardiac hypertrophy. The mechanisms involved in the regulation of Endog, however, are still to be elucidated. Therefore we hypothesised that Endog, being regulated by small regulatory non-coding RNAs called microRNAs (miRNAs), could contribute to the cardiac hypertrophy of the Hypertrophic Heart Rat (HHR), a human polygenic model of cardiac hypertrophy. From birth the HHR has less and smaller cardiomyocytes, which leads to hypertrophy and cardiac failure later in life. In this study, we examined genome-wide miRNA expression by Agilent Rat miRNA Microarray Kit Release 16.0 and Endog mRNA levels by real-time PCR in the left ventricle of neonatal HHR compared to age-matched rats from its authentic control, the Normal Heart Rat (NHR). Endog mRNA was significantly under-expressed in the HHR (fold change=−4.7; P=0.0001). Sixty-seven miRNAs (FDR P<0.05 and fold change>1.1) were differentially expressed between HHR and NHR (n=16). We then performed an in silico analysis to predict the miRNAs that are able to bind to the 3′ untranslated region of Endog mRNA, and therefore could regulate Endog levels. We discovered that the miRNAs let-7b, miR-338 and miR-347 are predicted to bind to Endog mRNA. Functional studies are being undertaken to determine whether these miRNAs can regulate Endog mRNA levels in vitro and their role in the pathological processes leading to cardiac hypertrophy. These miRNAs could be a new target for the prevention and treatment of cardiac hypertrophy in humans
Angiotensin II, Sympathetic nerve activity and chronic heart failure
- Authors: Wang, Yutang , Seto, Sai-Wang , Golledge, Jonathan
- Date: 2014
- Type: Text , Journal article
- Relation: Heart Failure Reviews Vol. 19, no. 2 (2014), p. 187-198
- Full Text: false
- Reviewed:
- Description: Sympathetic nerve activity has been reported to be increased in both humans and animals with chronic heart failure. One of the mechanisms believed to be responsible for this phenomenon is increased systemic and cerebral angiotensin II signaling. Plasma angiotensin II is increased in humans and animals with chronic heart failure. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic heart failure. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus, the rostral ventrolateral medulla and the area postrema. Blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the paraventricular nucleus. Injection of an angiotensin receptor blocker into the area postrema activates the sympathoinhibitory baroreflex. In peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity seen in chronic heart failure. Increased circulating angiotensin II during chronic heart failure may enhance the sympathoexcitatory chemoreflex and inhibit the sympathoinhibitory baroreflex. In addition, increased circulating angiotensin II can directly act on the central nervous system via the subfornical organ and the area postrema to increase sympathetic outflow. Inhibition of angiotensin II formation and its type 1 receptor has been shown to have beneficial effects in chronic heart failure patients. © 2012 Springer Science+Business Media New York.
Cardiovascular risk and androgenic anabolic steroids
- Authors: Sculthorpe, Nicholas , Grace, Fergal , Angell, Peter , Baker, Julien , George, Keith
- Date: 2013
- Type: Text , Journal article
- Relation: British Journal of Cardiac Nursing Vol. 7, no. 6 (2013), p. 266-275
- Full Text: false
- Reviewed:
- Description: Although several drugs are purported to improve exercise performance, androgenic anabolic steroids (AAS) are the most widespread. Furthermore, unlike other drugs, their use has expanded beyond competition, to non-competitive and recreational athletes. Correspondingly health professionals are more likely to come into contact with users of AAS than with users of other performance-enhancing drugs. While there are numerous reports outlining serious cardiovascular consequences to high-dose AAS abuse, this evidence is often limited by difficulties in gaining access to users due to the legal status of AAS. Additionally the co-abuse of other substances (as additional muscle mass enhancers, or to mitigate possible side effects) is a further confounding factor. This review examines the evidence for AAS having a negative effect on the cardiac and vascular tissue and the corresponding risk of developing cardiovascular disease. Possible mechanisms of action by which AAS bring about these changes are also discussed.
The acute effects of intense cardiorespiratory exercise on human telomerase reverse transcriptase and sirtuin 6 expression in white blood cells
- Authors: Chilton, Warrick , Marques, Francine , O'Brien, Brendan , Charchar, Fadi
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 30, no. e-Supplement (September 2012), p. e49
- Full Text: false
- Reviewed:
- Description: Background: Compelling epidemiological data demonstrates that regular physical exercise reduces cardiovascular mortality. Telomeres are specialised DNA structures located at the end of linear chromosomes where they protect them from degradation during DNA replication. Telomerase reverse transcriptase (TERT) expression is essential for telomere length maintenance. Accelerated telomere shortening is associated with increased risk of cardiovascular disease (CVD). Sirtuin 6 (SIRT6) is associated with increased longevity and protection against cardiac hypertrophy. Importantly, SIRT6 maintains genomic stability by specifically associating with telomeric chromatin. We hypothesized that acute cardiorespiratory exercise will affect the immediate expression of TERT and SIRT6. Methods: Twenty four healthy adults (19-39 years old) undertook 30 minutes of continuous treadmill running at 80% of maximal oxygen uptake (VO2max). Blood samples were taken before and immediately after exercise. Total RNA was extracted from white blood cells using TRIzol(R) LS reagent. TERT and SIRT6 mRNA expression were measured by real-time PCR. Results: There was no difference in TERT (P = 0.13) and SIRT6 (P = 0.73) mRNA levels immediately after acute cardiorespiratory exercise. Resting TERT levels, however, were negatively correlated with body mass index (BMI) (P = 0.03), waist to hip ratio (P = 0.01) and diastolic blood pressure (BP) (P = 0.05), while a marginal negative correlation was observed with systolic BP (P = 0.07). Conclusions: The results indicate that intense cardiorespiratory exercise does not result in acute modulation of TERT and SIRT6 mRNA. The negative correlations between BP, BMI, waist to hip ratio and TERT levels may provide a mechanistic insight into the established negative correlations between telomere length, hypertension and obesity.
- Description: C1
Factors contributing to COPD hospitalisations from 2010 to 2015 : Variation among rural and metropolitan Australians
- Authors: Terry, Daniel , Nguyen, Hoang , Kim, Jeong-Ah , Islam, Rafiqul
- Date: 2019
- Type: Text , Journal article
- Relation: Clinical Respiratory Journal Vol. 13, no. 5 (2019), p. 306-313
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- Description: Introduction: Rural and remote populations experience the greatest burden of chronic obstructive pulmonary disease (COPD), the fifth leading cause of death in Australia. Currently there is a need to prioritise health services to improve health outcomes among those at higher risk of COPD. Objectives: To investigate the differences in COPD hospitalisation between rural and urban populations and determine predictive factors contributing to COPD hospitalisation. Methods: Statewide hospitalisation data from 2010 to 2015 were obtained through the Victorian Admitted Episodes Dataset and other key data sets. The rates of hospitalisation were analysed using hierarchical multiple regression to examine the association between COPD hospitalisations and a number of predictor variables. Results: The highest COPD incidence occurred in metropolitan males aged 85 years of age and older (35.092 hospitalisations per 1000 population). Among metropolitan residents, smoking, population density and household income had a significant association with COPD hospitalisations for both sexes. Among rural males, smoking rates, household income and rural land use (farming) were significant predictors of COPD hospitalisations. There was an overall stability in statewide COPD hospitalisation over the 5 years to 2015, P = 0.420. Conclusion: This investigation highlights many rural and regional areas have much lower COPD hospitalisation rates than metropolitan areas. Between males and females, there are heterogenetic factors that contribute to the significant variation associated with COPD hospitalisation in metropolitan and rural areas, such as rural land use among rural males. This indicates that risk factor assessments, beyond smoking alone, need to be individualised and prioritised in practice to optimise care.