Wnt signaling pathway inhibitor Sclerostin inhibits angiotensin II-induced aortic aneurysm and atherosclerosis
- Krishna, Smriti, Seto, Sai-Wang, Jose, Roby, Li, Jiaze, Morton, Susan, Biros, Erik, Wang, Yutang, Nsengiyumva, Vianne, Lindeman, Jan, Loots, Gabriela, Rush, Catherine, Craig, Jeffrey, Golledge, Jonathan
- Authors: Krishna, Smriti , Seto, Sai-Wang , Jose, Roby , Li, Jiaze , Morton, Susan , Biros, Erik , Wang, Yutang , Nsengiyumva, Vianne , Lindeman, Jan , Loots, Gabriela , Rush, Catherine , Craig, Jeffrey , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 37, no. 3 (2017), p. 553-566
- Full Text:
- Reviewed:
- Description: Objective-Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. Approach and Results-SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOSTTg. ApoE(-/-)) and administration of recombinant mouse Sost inhibited angiotensin II-induced AA and atherosclerosis. Serum concentrations of several proinflammatory cytokines were significantly reduced in SOSTTg. ApoE(-/-) mice. Compared with controls, the aortas of mice receiving recombinant mouse Sost and SOSTTg. ApoE(-/-) mice showed reduced matrix degradation, reduced elastin breaks, and preserved collagen. Decreased inflammatory cell infiltration and a reduction in the expression of wingless-type mouse mammary virus integration site/beta-catenin responsive genes, including matrix metalloproteinase-9, osteoprotegerin, and osteopontin, were observed in the aortas of SOSTTg. ApoE(-/-) mice. SOST expression was downregulated and the winglesstype mouse mammary virus integration site/beta-catenin pathway was activated in human AA samples. The cytosinephosphate- guanine islands in the SOST gene promoter showed significantly higher methylation in human AA samples compared with controls. Incubation of vascular smooth muscle cells with the demethylating agent 5-azacytidine resulted in upregulation of SOST, suggesting that SOST is epigenetically regulated. Conclusions-This study identifies that SOST is expressed in the aorta and downregulated in human AA possibly because of epigenetic silencing. Upregulating SOST inhibits AA and atherosclerosis development, with potential important implications for treating these vascular diseases.
- Authors: Krishna, Smriti , Seto, Sai-Wang , Jose, Roby , Li, Jiaze , Morton, Susan , Biros, Erik , Wang, Yutang , Nsengiyumva, Vianne , Lindeman, Jan , Loots, Gabriela , Rush, Catherine , Craig, Jeffrey , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 37, no. 3 (2017), p. 553-566
- Full Text:
- Reviewed:
- Description: Objective-Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. Approach and Results-SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOSTTg. ApoE(-/-)) and administration of recombinant mouse Sost inhibited angiotensin II-induced AA and atherosclerosis. Serum concentrations of several proinflammatory cytokines were significantly reduced in SOSTTg. ApoE(-/-) mice. Compared with controls, the aortas of mice receiving recombinant mouse Sost and SOSTTg. ApoE(-/-) mice showed reduced matrix degradation, reduced elastin breaks, and preserved collagen. Decreased inflammatory cell infiltration and a reduction in the expression of wingless-type mouse mammary virus integration site/beta-catenin responsive genes, including matrix metalloproteinase-9, osteoprotegerin, and osteopontin, were observed in the aortas of SOSTTg. ApoE(-/-) mice. SOST expression was downregulated and the winglesstype mouse mammary virus integration site/beta-catenin pathway was activated in human AA samples. The cytosinephosphate- guanine islands in the SOST gene promoter showed significantly higher methylation in human AA samples compared with controls. Incubation of vascular smooth muscle cells with the demethylating agent 5-azacytidine resulted in upregulation of SOST, suggesting that SOST is epigenetically regulated. Conclusions-This study identifies that SOST is expressed in the aorta and downregulated in human AA possibly because of epigenetic silencing. Upregulating SOST inhibits AA and atherosclerosis development, with potential important implications for treating these vascular diseases.
Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22
- Prestes, Priscilla, Marques, Francine, Lopez-Campos, Guillermo, Booth, Scott, McGlynn, Maree, Lewandowski, Paul, Delbridge, Lea, Harrap, Stephen, Charchar, Fadi
- Authors: Prestes, Priscilla , Marques, Francine , Lopez-Campos, Guillermo , Booth, Scott , McGlynn, Maree , Lewandowski, Paul , Delbridge, Lea , Harrap, Stephen , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 34, no. 5 (May 2016), p. 950-958
- Relation: http://purl.org/au-research/grants/nhmrc/1034371
- Full Text:
- Reviewed:
- Description: Background:Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR).Methods and results:To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHRxNHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P<0.05) and reduced protein expression. Trim55 mRNA levels were negatively correlated with LV mass in the F2 cross (r=-0.16, P=0.025). In exon nine of Trim55 in HHR, we found one missense mutation that functionally alters protein structure. This mutation was strongly associated with Trim55 mRNA expression in F2 rats (F=10.35, P<0.0001). Similarly, in humans, we found reduced Trim55 expression in hearts of subjects with idiopathic dilated cardiomyopathy.Conclusion:Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure.
- Authors: Prestes, Priscilla , Marques, Francine , Lopez-Campos, Guillermo , Booth, Scott , McGlynn, Maree , Lewandowski, Paul , Delbridge, Lea , Harrap, Stephen , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 34, no. 5 (May 2016), p. 950-958
- Relation: http://purl.org/au-research/grants/nhmrc/1034371
- Full Text:
- Reviewed:
- Description: Background:Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR).Methods and results:To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHRxNHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P<0.05) and reduced protein expression. Trim55 mRNA levels were negatively correlated with LV mass in the F2 cross (r=-0.16, P=0.025). In exon nine of Trim55 in HHR, we found one missense mutation that functionally alters protein structure. This mutation was strongly associated with Trim55 mRNA expression in F2 rats (F=10.35, P<0.0001). Similarly, in humans, we found reduced Trim55 expression in hearts of subjects with idiopathic dilated cardiomyopathy.Conclusion:Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure.
The prevalence of cardiovascular risk factors and cardiovascular disease among primary care patients in Poland : results from the LIPIDOGRAM2015 study
- Jóźwiak, Jacek, Studziński, Krzysztof, Tomasik, Tomasz, Windak, Adam, Charchar, Fadi
- Authors: Jóźwiak, Jacek , Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: Atherosclerosis Supplements Vol. 42, no. (2020), p. e15-e24
- Full Text:
- Reviewed:
- Description: Background and aim: To estimate the prevalence of cardiovascular (CV) disease and CV risk factors among Polish patients. Methods: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the 4th quarter of 2015 and 1st and 2nd quarters of 2016; 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. Results: Nearly 19% of men and approximately 12% of women had cardiovascular disease (CVD). Over 60% of the recruited patients had hypertension (HTN), >80% had dyslipidaemia and <15% of patients were diagnosed with diabetes (DM). All of these disorders were more frequent in men. In 80% of patients the waist circumference exceed norm for the European population. Less than half of the patients were current smokers or had smoked in the past. Patients with CVD had significantly higher blood pressure and glucose levels but lower low density lipoprotein-cholesterol level. Conclusions: The prevalence of CVD and CV risk factors among patients in Poland is high. CVD is more common in men than in women. The most common CV risk factors are excess waist circumference, dyslipidaemia and HTN. Family physicians should conduct activities to prevent, diagnose early and treat CVD in the primary health care population. © 2021 Elsevier B.V. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Jóźwiak, Jacek , Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: Atherosclerosis Supplements Vol. 42, no. (2020), p. e15-e24
- Full Text:
- Reviewed:
- Description: Background and aim: To estimate the prevalence of cardiovascular (CV) disease and CV risk factors among Polish patients. Methods: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the 4th quarter of 2015 and 1st and 2nd quarters of 2016; 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. Results: Nearly 19% of men and approximately 12% of women had cardiovascular disease (CVD). Over 60% of the recruited patients had hypertension (HTN), >80% had dyslipidaemia and <15% of patients were diagnosed with diabetes (DM). All of these disorders were more frequent in men. In 80% of patients the waist circumference exceed norm for the European population. Less than half of the patients were current smokers or had smoked in the past. Patients with CVD had significantly higher blood pressure and glucose levels but lower low density lipoprotein-cholesterol level. Conclusions: The prevalence of CVD and CV risk factors among patients in Poland is high. CVD is more common in men than in women. The most common CV risk factors are excess waist circumference, dyslipidaemia and HTN. Family physicians should conduct activities to prevent, diagnose early and treat CVD in the primary health care population. © 2021 Elsevier B.V. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
The efficacy of different modes of analgesia in postoperative pain management and early mobilization in postoperative cardiac surgical patients : A systematic review
- Nachiyunde, Brenda, Lam, Louisa
- Authors: Nachiyunde, Brenda , Lam, Louisa
- Date: 2018
- Type: Text , Journal article , Review
- Relation: Annals of Cardiac Anaesthesia Vol. 21, no. 4 (2018), p. 371-375
- Full Text:
- Reviewed:
- Description: Cardiac surgery induces severe postoperative pain and impairment of pulmonary function, increases the length of stay (LOS) in hospital, and increases mortality and morbidity; therefore, evaluation of the evidence is needed to assess the comparative benefits of different techniques of pain management, to guide clinical practice, and to identify areas of further research. A systematic search of the Cochrane Central Register of Controlled Trials, DARE database, Joanna Briggs Institute, Google scholar, PUBMED, MEDLINE, EMBASE, Academic OneFile, SCOPUS, and Academic search premier was conducted retrieving 1875 articles. This was for pain management postcardiac surgery in intensive care. Four hundred and seventy-one article titles and 266 abstracts screened, 52 full text articles retrieved for critical appraisal, and ten studies were included including 511 patients. Postoperative pain (patient reported), complications, and LOS in intensive care and the hospital were evaluated. Anesthetic infiltrations and intercostal or parasternal blocks are recommended the immediate postoperative period (4-6 h), and patient-controlled analgesia (PCA) and local subcutaneous anesthetic infusions are recommended immediate postoperative and 24-72 h postcardiac surgery. However, the use of mixed techniques, that is, PCA with opioids and local anesthetic subcutaneous infusions might be the way to go in pain management postcardiac surgery to avoid oversedation and severe nausea and vomiting from the narcotics. Adequate studies in the use of ketamine for pain management postcardiac surgery need to be done and it should be used cautiously.
- Authors: Nachiyunde, Brenda , Lam, Louisa
- Date: 2018
- Type: Text , Journal article , Review
- Relation: Annals of Cardiac Anaesthesia Vol. 21, no. 4 (2018), p. 371-375
- Full Text:
- Reviewed:
- Description: Cardiac surgery induces severe postoperative pain and impairment of pulmonary function, increases the length of stay (LOS) in hospital, and increases mortality and morbidity; therefore, evaluation of the evidence is needed to assess the comparative benefits of different techniques of pain management, to guide clinical practice, and to identify areas of further research. A systematic search of the Cochrane Central Register of Controlled Trials, DARE database, Joanna Briggs Institute, Google scholar, PUBMED, MEDLINE, EMBASE, Academic OneFile, SCOPUS, and Academic search premier was conducted retrieving 1875 articles. This was for pain management postcardiac surgery in intensive care. Four hundred and seventy-one article titles and 266 abstracts screened, 52 full text articles retrieved for critical appraisal, and ten studies were included including 511 patients. Postoperative pain (patient reported), complications, and LOS in intensive care and the hospital were evaluated. Anesthetic infiltrations and intercostal or parasternal blocks are recommended the immediate postoperative period (4-6 h), and patient-controlled analgesia (PCA) and local subcutaneous anesthetic infusions are recommended immediate postoperative and 24-72 h postcardiac surgery. However, the use of mixed techniques, that is, PCA with opioids and local anesthetic subcutaneous infusions might be the way to go in pain management postcardiac surgery to avoid oversedation and severe nausea and vomiting from the narcotics. Adequate studies in the use of ketamine for pain management postcardiac surgery need to be done and it should be used cautiously.
The effect of bronchial thermoplasty on airway volume measured 12 months post-procedure
- Langton, David, Banks, Ceri, Noble, Peter, Plummer, Virginia, Thien, Francis, Donovan, Graham
- Authors: Langton, David , Banks, Ceri , Noble, Peter , Plummer, Virginia , Thien, Francis , Donovan, Graham
- Date: 2020
- Type: Text , Journal article
- Relation: Erj Open Research Vol. 6, no. 4 (Oct 2020), p. 9
- Full Text:
- Reviewed:
- Description: Bronchial thermoplasty induces atrophy of the airway smooth muscle layer, but the mechanism whereby this improves patient health is unclear. In this study, we use computed tomography (CT) to evaluate the effects of bronchial thermoplasty on airway volume 12 months post-procedure. 10 consecutive patients with severe asthma were evaluated at baseline by the Asthma Control Questionnaire (ACQ), and high-resolution CT at total lung capacity (TLC) and functional residual capacity (FRC). The CT protocol was repeated 4 weeks after the left lung had been treated by bronchial thermoplasty, but prior to right lung treatment, and then again 12 months after both lungs were treated. The CT data were also used to model the implications of including the right middle lobe (RML) in the treatment field. The mean patient age was 62.7 +/- 7.7 years and forced expiratory volume in 1 s (FEV1) 42.9 +/- 11.5% predicted. 12 months post-bronchial-thermoplasty, the ACQ improved, from 3.4 +/- 1.0 to 1.5 +/- 0.9 (p=0.001), as did the frequency of oral steroid-requiring exacerbations (p=0.008). The total airway volume increased 12 months after bronchial thermoplasty in both the TLC (p=0.03) and the FRC scans (p=0.02). No change in airway volume was observed in the untreated central airways. In the bronchial thermoplasty-treated distal airways, increases in airway volume of 38.4 +/- 31.8% at TLC (p=0.03) and 30.0 +/- 24.8% at FRC (p=0.01) were observed. The change in distal airway volume was correlated with the improvement in ACQ (r=-0.71, p=0.02). Modelling outputs demonstrated that treating the RML conferred no additional benefit. Bronchial thermoplasty induces long-term increases in airway volume, which correlate with symptomatic improvement.
- Authors: Langton, David , Banks, Ceri , Noble, Peter , Plummer, Virginia , Thien, Francis , Donovan, Graham
- Date: 2020
- Type: Text , Journal article
- Relation: Erj Open Research Vol. 6, no. 4 (Oct 2020), p. 9
- Full Text:
- Reviewed:
- Description: Bronchial thermoplasty induces atrophy of the airway smooth muscle layer, but the mechanism whereby this improves patient health is unclear. In this study, we use computed tomography (CT) to evaluate the effects of bronchial thermoplasty on airway volume 12 months post-procedure. 10 consecutive patients with severe asthma were evaluated at baseline by the Asthma Control Questionnaire (ACQ), and high-resolution CT at total lung capacity (TLC) and functional residual capacity (FRC). The CT protocol was repeated 4 weeks after the left lung had been treated by bronchial thermoplasty, but prior to right lung treatment, and then again 12 months after both lungs were treated. The CT data were also used to model the implications of including the right middle lobe (RML) in the treatment field. The mean patient age was 62.7 +/- 7.7 years and forced expiratory volume in 1 s (FEV1) 42.9 +/- 11.5% predicted. 12 months post-bronchial-thermoplasty, the ACQ improved, from 3.4 +/- 1.0 to 1.5 +/- 0.9 (p=0.001), as did the frequency of oral steroid-requiring exacerbations (p=0.008). The total airway volume increased 12 months after bronchial thermoplasty in both the TLC (p=0.03) and the FRC scans (p=0.02). No change in airway volume was observed in the untreated central airways. In the bronchial thermoplasty-treated distal airways, increases in airway volume of 38.4 +/- 31.8% at TLC (p=0.03) and 30.0 +/- 24.8% at FRC (p=0.01) were observed. The change in distal airway volume was correlated with the improvement in ACQ (r=-0.71, p=0.02). Modelling outputs demonstrated that treating the RML conferred no additional benefit. Bronchial thermoplasty induces long-term increases in airway volume, which correlate with symptomatic improvement.
- Chilton, Warrick, Marques, Francine, O'Brien, Brendan, Charchar, Fadi
- 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
Single-sided renal denervation may be not suitable for patients with significant renal artery stenosis
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Journal article , Letter
- Relation: Clinical Research in Cardiology Vol. 103, no. 11 (2014), p. 950-951
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Journal article , Letter
- Relation: Clinical Research in Cardiology Vol. 103, no. 11 (2014), p. 950-951
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
Short and long term mortality rates after a lower limb amputation
- Fortington, Lauren, Geertzen, Jan, Van Netten, Jaap, Postema, Klaas, Rommers, Gerardus, Dijkstra, Pieter
- 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
- 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
- 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
Self-care interventions that reduce hospital readmissions in patients with heart failure; towards the identification of change agents
- Toukhsati, Samia, Jaarsma, Tiny, Babu, Abraham, Driscoll, Andrea, Hare, David
- Authors: Toukhsati, Samia , Jaarsma, Tiny , Babu, Abraham , Driscoll, Andrea , Hare, David
- Date: 2019
- Type: Text , Journal article , Review
- Relation: Clinical Medicine Insights: Cardiology Vol. 13, no. (2019), p. 1-8
- Full Text:
- Reviewed:
- Description: Unplanned hospital readmissions are the most important, preventable cost in heart failure (HF) health economics. Current professional guidelines recommend that patient self-care is an important means by which to reduce this burden. Patients with HF should be engaged in their care such as by detecting, monitoring, and managing their symptoms. A variety of educational and behavioural interventions have been designed and implemented by health care providers to encourage and support patient self-care. Meta-analyses support the use of self-care interventions to improve patient self-care and reduce hospital readmissions; however, efficacy is variable. The aim of this review was to explore methods to achieve greater clarity and consistency in the development and reporting of self-care interventions to enable ‘change agents’ to be identified. We conclude that advancement in this field requires more explicit integration and reporting on the behaviour change theories that inform the design of self-care interventions and the selection of behaviour change techniques. The systematic application of validated checklists, such as the Theory Coding Scheme and the CALO-RE taxonomy, will improve the systematic testing and refinement of interventions to enable ‘change agent/s’ to be identified and optimised.
- Authors: Toukhsati, Samia , Jaarsma, Tiny , Babu, Abraham , Driscoll, Andrea , Hare, David
- Date: 2019
- Type: Text , Journal article , Review
- Relation: Clinical Medicine Insights: Cardiology Vol. 13, no. (2019), p. 1-8
- Full Text:
- Reviewed:
- Description: Unplanned hospital readmissions are the most important, preventable cost in heart failure (HF) health economics. Current professional guidelines recommend that patient self-care is an important means by which to reduce this burden. Patients with HF should be engaged in their care such as by detecting, monitoring, and managing their symptoms. A variety of educational and behavioural interventions have been designed and implemented by health care providers to encourage and support patient self-care. Meta-analyses support the use of self-care interventions to improve patient self-care and reduce hospital readmissions; however, efficacy is variable. The aim of this review was to explore methods to achieve greater clarity and consistency in the development and reporting of self-care interventions to enable ‘change agents’ to be identified. We conclude that advancement in this field requires more explicit integration and reporting on the behaviour change theories that inform the design of self-care interventions and the selection of behaviour change techniques. The systematic application of validated checklists, such as the Theory Coding Scheme and the CALO-RE taxonomy, will improve the systematic testing and refinement of interventions to enable ‘change agent/s’ to be identified and optimised.
Screening, referral and treatment of depression by Australian cardiologists
- Hare, David, Stewart, Andrew, Driscoll, Andrea, Mathews, Stephanie, Toukhsati, Samia
- 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.
- Moran, Corey, Biros, Erik, Krishna, Smriti, Wang, Yutang, Tikellis, Chris, Moxon, Joseph, Cooper, Mark, Norman, Paul, Burrell, Louise, Thomas, Merlin, Golledge, Jonathan
- Authors: Moran, Corey , Biros, Erik , Krishna, Smriti , Wang, Yutang , Tikellis, Chris , Moxon, Joseph , Cooper, Mark , Norman, Paul , Burrell, Louise , Thomas, Merlin , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 37, no. 11 (2017), p. 2195-2203
- Full Text: false
- Reviewed:
- Description: Objective-Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. Approach and Results-Ace2 deletion in apolipoprotein-deficient mice (ApoE(-/-)Ace2(-/y)) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers. In humans, serum ACE2 activity was negatively associated with AAA diagnosis. ACE2 expression was lower in infrarenal biopsies of patients with AAA than organ donors. AAA was more severe in ApoE (-/-)Ace2(-/y) mice compared with controls in 2 experimental models. Resveratrol (0.05/100-g chow) inhibited growth of pre-established AAAs in ApoE(-/-) mice fed high-fat chow and infused with angiotensin II continuously for 56 days. Reduced suprarenal aorta dilatation in mice receiving resveratrol was associated with elevated serum ACE2 and increased suprarenal aorta tissue levels of ACE2 and sirtuin 1 activity. In addition, the relative phosphorylation of Akt and ERK (extracellular signal-regulated kinase) 1/2 within suprarenal aorta tissue and gene expression for nuclear factor of kappa light polypeptide gene enhancer in B cells 1, angiotensin type-1 receptor, and metallopeptidase 2 and 9 were significantly reduced. Upregulation of ACE2 in human aortic smooth muscle cells by resveratrol in vitro was sirtuin 1-dependent. Conclusions-This study provides experimental evidence of an important role for ACE2 in limiting AAA development and growth. Resveratrol upregulated ACE2 and inhibited AAA growth in a mouse model.
Renal nerves contribute to hypertension in Schlager BPH/2J mice
- Gueguen, Cindy, Jackson, Kristy, Marques, Francine, Eikelis, Nina, Phillips, Sarah, Stevenson, Emily, Charchar, Fadi, Lambert, Gavin, Davern, Pamela, Head, Geoffrey
- Authors: Gueguen, Cindy , Jackson, Kristy , Marques, Francine , Eikelis, Nina , Phillips, Sarah , Stevenson, Emily , Charchar, Fadi , Lambert, Gavin , Davern, Pamela , Head, Geoffrey
- Date: 2019
- Type: Text , Journal article
- Relation: Hypertension Research Vol. 42, no. 3 (2019), p. 306-318
- Full Text:
- Reviewed:
- Description: Schlager mice (BPH/2J) are hypertensive due to a greater contribution of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS). The kidneys of BPH/2J are hyper-innervated suggesting renal nerves may contribute to the hypertension. We therefore determined the effect of bilateral renal denervation (RD) on hypertension in BPH/2J. Mean arterial pressure (MAP) was measured by radiotelemetry before and for 3 weeks after RD in BPH/2J and BPN/3J. The effects of pentolinium and enalaprilat were examined to determine the contribution of the SNS and RAS, respectively. After 3 weeks, MAP was −10.9 ± 2.1 mmHg lower in RD BPH/2J compared to baseline and −2.1 ± 2.2 mmHg in sham BPH/2J (P < 0.001, n = 8–10). RD had no effect in BPN/3J (P > 0.1). The depressor response to pentolinium was greater in BPH/2J than BPN/3J, but in both cases the response in RD mice was similar to sham. Enalaprilat decreased MAP more in RD BPH/2J compared to sham (−12 vs −3 mmHg, P < 0.001) but had no effect in BPN/3J. RD reduced renal noradrenaline in both strains but more so in BPH/2J. RD reduced renin mRNA and protein, but not plasma renin in BPH/2J to levels comparable with BPN/3J mice. We conclude that renal nerves contribute to hypertension in BPH mice as RD induced a sustained fall in MAP, which was associated with a reduction of intrarenal renin expression. The lack of inhibition of the depressor effects of pentolinium and enalaprilat by RD suggests that vasoconstrictor effects of the SNS or RAS are not involved.
- Authors: Gueguen, Cindy , Jackson, Kristy , Marques, Francine , Eikelis, Nina , Phillips, Sarah , Stevenson, Emily , Charchar, Fadi , Lambert, Gavin , Davern, Pamela , Head, Geoffrey
- Date: 2019
- Type: Text , Journal article
- Relation: Hypertension Research Vol. 42, no. 3 (2019), p. 306-318
- Full Text:
- Reviewed:
- Description: Schlager mice (BPH/2J) are hypertensive due to a greater contribution of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS). The kidneys of BPH/2J are hyper-innervated suggesting renal nerves may contribute to the hypertension. We therefore determined the effect of bilateral renal denervation (RD) on hypertension in BPH/2J. Mean arterial pressure (MAP) was measured by radiotelemetry before and for 3 weeks after RD in BPH/2J and BPN/3J. The effects of pentolinium and enalaprilat were examined to determine the contribution of the SNS and RAS, respectively. After 3 weeks, MAP was −10.9 ± 2.1 mmHg lower in RD BPH/2J compared to baseline and −2.1 ± 2.2 mmHg in sham BPH/2J (P < 0.001, n = 8–10). RD had no effect in BPN/3J (P > 0.1). The depressor response to pentolinium was greater in BPH/2J than BPN/3J, but in both cases the response in RD mice was similar to sham. Enalaprilat decreased MAP more in RD BPH/2J compared to sham (−12 vs −3 mmHg, P < 0.001) but had no effect in BPN/3J. RD reduced renal noradrenaline in both strains but more so in BPH/2J. RD reduced renin mRNA and protein, but not plasma renin in BPH/2J to levels comparable with BPN/3J mice. We conclude that renal nerves contribute to hypertension in BPH mice as RD induced a sustained fall in MAP, which was associated with a reduction of intrarenal renin expression. The lack of inhibition of the depressor effects of pentolinium and enalaprilat by RD suggests that vasoconstrictor effects of the SNS or RAS are not involved.
Prevalence and risk factors of ischaemic stroke in the young : a regional Australian perspective
- Siriratnam, Pakeeran, Godfrey, Amelia, O’Connor, Ellie, Pearce, Dora, Hu, Chih, Low, Ashlea, Hair, Casey, Oqueli, Ernesto, Sharma, Anand, Kraemer, Thomas, Sahathevan, Ramesh
- Authors: Siriratnam, Pakeeran , Godfrey, Amelia , O’Connor, Ellie , Pearce, Dora , Hu, Chih , Low, Ashlea , Hair, Casey , Oqueli, Ernesto , Sharma, Anand , Kraemer, Thomas , Sahathevan, Ramesh
- Date: 2020
- Type: Text , Journal article
- Relation: Internal Medicine Journal Vol. 50, no. 6 (2020), p. 698-704
- Full Text:
- Reviewed:
- Description: Background: There is no universally accepted age cut-off for defining young strokes. Aims: We aimed to determine, based on the profile of young stroke patients in our regional centre, an appropriate age cut-off for young strokes. Methods: A retrospective analysis of all ischaemic stroke patients admitted to our centre from 2015 to 2017. We identified 391 ischaemic stroke patients; 30 patients between the ages of ≤50, 40 between 51–60 inclusive and 321 ≥ 61 years of age. We collected data on demographic profiles, risk factors and stroke classification using the Trial of Org 10 172 in Acute Stroke Treatment criteria. Results: We found significant differences between the ≤50 and ≥61 age groups for most of the risk factors and similarities between the 51–60 inclusive and ≥ 61 age groups. At least one of the six risk factors assessed in the study was present in 86.7% of the youngest group, 97.5% of the intermediate age group and 97.2% in the oldest group. In terms of the mechanisms of stroke, the youngest and oldest age groups in our study differed in the prevalence of cryptogenic, cardioembolic and other causes of stroke. The middle and older age groups had similar mechanisms of stroke. Conclusions: The prevalence of vascular risk factors and mechanisms of stroke likewise differed significantly across age groups. This study suggests that 50 years is an appropriate age cut-off for defining young strokes and reinforces the importance of primary prevention in all age groups. © 2019 Royal Australasian College of Physicians
- Authors: Siriratnam, Pakeeran , Godfrey, Amelia , O’Connor, Ellie , Pearce, Dora , Hu, Chih , Low, Ashlea , Hair, Casey , Oqueli, Ernesto , Sharma, Anand , Kraemer, Thomas , Sahathevan, Ramesh
- Date: 2020
- Type: Text , Journal article
- Relation: Internal Medicine Journal Vol. 50, no. 6 (2020), p. 698-704
- Full Text:
- Reviewed:
- Description: Background: There is no universally accepted age cut-off for defining young strokes. Aims: We aimed to determine, based on the profile of young stroke patients in our regional centre, an appropriate age cut-off for young strokes. Methods: A retrospective analysis of all ischaemic stroke patients admitted to our centre from 2015 to 2017. We identified 391 ischaemic stroke patients; 30 patients between the ages of ≤50, 40 between 51–60 inclusive and 321 ≥ 61 years of age. We collected data on demographic profiles, risk factors and stroke classification using the Trial of Org 10 172 in Acute Stroke Treatment criteria. Results: We found significant differences between the ≤50 and ≥61 age groups for most of the risk factors and similarities between the 51–60 inclusive and ≥ 61 age groups. At least one of the six risk factors assessed in the study was present in 86.7% of the youngest group, 97.5% of the intermediate age group and 97.2% in the oldest group. In terms of the mechanisms of stroke, the youngest and oldest age groups in our study differed in the prevalence of cryptogenic, cardioembolic and other causes of stroke. The middle and older age groups had similar mechanisms of stroke. Conclusions: The prevalence of vascular risk factors and mechanisms of stroke likewise differed significantly across age groups. This study suggests that 50 years is an appropriate age cut-off for defining young strokes and reinforces the importance of primary prevention in all age groups. © 2019 Royal Australasian College of Physicians
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
- Abbott, Jo-Anne, Klein, Britt, McLaren, Suzanne, Austin, David, Molloy, Mari, Meyer, Denny, McLeod, Bronte
- 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.
- 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.
Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia
- 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
- 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
- Jackson, Kristy, Gueguen, Cindy, Lim, Kyungjoon, Eikelis, Nina, Stevenson, Emily, Charchar, Fadi, Lambert, Gavin, Burke, Sandra, Paterson, Madeleine, Marques, Francine, Head, Geoffrey
- 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).
- Marques, Francine, Campain, Anna, Yang, Yee, Morris, Brian
- 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
Meaningful and effective consultation and the construction industry of Victoria, Australia
- Ayers, Gerard, Culvenor, John, Sillitoe, Jim, Else, Dennis
- 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
May measurement month 2019 the global blood pressure screening campaign of the International Society of Hypertension
- Beaney, Thomas, Schutte, Aletta, Stergiou, George, Borghi, Claudio, Burger, Dylan, Charchar, Fadi, Cro, Suzie, Diaz, Alejandro, Damasceno, Albertino, Espeche, Walter, Jose, Arun, Khan, Nadia, Kokubo, Yoshihiro, Maheshwari, Anuj, Marin, Marcos, More, Arun, Neupane, Dinesh, Nilsson, Peter, Patil, Mansi, Prabhakaran, Dorairaj, Ramirez, Agustin, Rodriguez, Pablo, Schlaich, Markus, Steckelings, Ulrike, Tomaszewski, Maciej, Unger, Thomas, Wainford, Richard, Wang, Jiguang, Williams, Bryan, Poulter, Neil, M. M. M. Investigators
- Authors: Beaney, Thomas , Schutte, Aletta , Stergiou, George , Borghi, Claudio , Burger, Dylan , Charchar, Fadi , Cro, Suzie , Diaz, Alejandro , Damasceno, Albertino , Espeche, Walter , Jose, Arun , Khan, Nadia , Kokubo, Yoshihiro , Maheshwari, Anuj , Marin, Marcos , More, Arun , Neupane, Dinesh , Nilsson, Peter , Patil, Mansi , Prabhakaran, Dorairaj , Ramirez, Agustin , Rodriguez, Pablo , Schlaich, Markus , Steckelings, Ulrike , Tomaszewski, Maciej , Unger, Thomas , Wainford, Richard , Wang, Jiguang , Williams, Bryan , Poulter, Neil , M. M. M. Investigators
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 76, no. 2 (Aug 2020), p. 333-341
- Full Text:
- Reviewed:
- Description: Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (>= 18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure >= 140 mm Hg, or a diastolic blood pressure >= 90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.
- Authors: Beaney, Thomas , Schutte, Aletta , Stergiou, George , Borghi, Claudio , Burger, Dylan , Charchar, Fadi , Cro, Suzie , Diaz, Alejandro , Damasceno, Albertino , Espeche, Walter , Jose, Arun , Khan, Nadia , Kokubo, Yoshihiro , Maheshwari, Anuj , Marin, Marcos , More, Arun , Neupane, Dinesh , Nilsson, Peter , Patil, Mansi , Prabhakaran, Dorairaj , Ramirez, Agustin , Rodriguez, Pablo , Schlaich, Markus , Steckelings, Ulrike , Tomaszewski, Maciej , Unger, Thomas , Wainford, Richard , Wang, Jiguang , Williams, Bryan , Poulter, Neil , M. M. M. Investigators
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 76, no. 2 (Aug 2020), p. 333-341
- Full Text:
- Reviewed:
- Description: Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (>= 18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure >= 140 mm Hg, or a diastolic blood pressure >= 90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.