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
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- 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
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
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- 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 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
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- 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.
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
- Full Text:
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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.
Cardiac response to exercise in normal ageing : What can we learn from masters athletes?
- Authors: Beaumont, Alexander , Campbell, Amy , Grace, Fergal , Sculthorpe, Nicholas
- Date: 2018
- Type: Text , Journal article , Review
- Relation: Current Cardiology Reviews Vol. 14, no. 4 (2018), p. 245-253
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- Description: Background: Ageing is associated with an inexorable decline in cardiac and vascular function, resulting in an increased risk of Cardiovascular Disease (CVD). Lifestyle factors such as exercise have emerged as a primary therapeutic target in the prevention of CVD, yet older individuals are frequently reported as being the least active, with few meeting the recommended physical activity guidelines. In contrast, well trained older individuals (Masters athletes) have superior functional capacity than their sedentary peers and are often comparable with young non-athletes. Therefore, the 'masters' athlete may be viewed as a unique non-pharmacological model which may allow researchers to disentangle the inexorable from the preventable and the magnitude of the unavoidable 'true' reduction in cardiac function due to ageing. Conclusion: This review examines evidence from studies which have compared cardiac structure and function in well trained older athletes, with age-matched controls but otherwise healthy. © 2018 Bentham Science Publishers.
Early post-operative mortality after major lower limb amputation : A systematic review of population and regional based studies
- Authors: Van Netten, Jaap , Fortington, Lauren , Hinchliffe, Robert , Hijmans, Juha
- Date: 2016
- Type: Text , Journal article
- Relation: European Journal of Vascular and Endovascular Surgery Vol. 51, no. 2 (2016), p. 248-258
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- Description: Objective Lower limb amputation is often associated with a high risk of early post-operative mortality. Mortality rates are also increasingly being put forward as a possible benchmark for surgical performance. The primary aim of this systematic review is to investigate early post-operative mortality following a major lower limb amputation in population/regional based studies, and reported factors that might influence these mortality outcomes. Methods Embase, PubMed, Cinahl and Psycinfo were searched for publications in any language on 30 day or in hospital mortality after major lower limb amputation in population/regional based studies. PRISMA guidelines were followed. A self developed checklist was used to assess quality and susceptibility to bias. Summary data were extracted for the percentage of the population who died; pooling of quantitative results was not possible because of methodological differences between studies. Results Of the 9,082 publications identified, results were included from 21. The percentage of the population undergoing amputation who died within 30 days ranged from 7% to 22%, the in hospital equivalent was 4-20%. Transfemoral amputation and older age were found to have a higher proportion of early post-operative mortality, compared with transtibial and younger age, respectively. Other patient factors or surgical treatment choices related to increased early post-operative mortality varied between studies. Conclusions Early post-operative mortality rates vary from 4% to 22%. There are very limited data presented for patient related factors (age, comorbidities) that influence mortality. Even less is known about factors related to surgical treatment choices, being limited to amputation level. More information is needed to allow comparison across studies or for any benchmarking of acceptable mortality rates. Agreement is needed on key factors to be reported. © 2015 European Society for Vascular Surgery.
Cognitive behaviour therapy for older adults experiencing insomnia and depression in a community mental health setting: Study protocol for a randomised controlled trial
- Authors: Sadler, Paul , McLaren, Suzanne , Klein, Britt , Jenkins, Megan , Harvey, Jack
- Date: 2015
- Type: Text , Journal article
- Relation: Trials Vol. 16, no. 1 (2015), p.1-12
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- Description: Background: Cognitive behaviour therapy for insomnia (CBT-I) is a well-established treatment; however, the evidence is largely limited to homogenous samples. Although emerging research has indicated that CBT-I is also effective for comorbid insomnia, CBT-I has not been tested among a complex sample of older adults with comorbid insomnia and depression. Furthermore, no study has explored whether modifying CBT-I to target associated depressive symptoms could potentially enhance sleep and mood outcomes. Therefore, this study aims to report a protocol designed to test whether an advanced form of CBT for insomnia and depression (CBT-I-D) is more effective at reducing insomnia and depressive symptoms compared to a standard CBT-I and psychoeducation control group (PCG) for older adults in a community mental health setting. Methods/Design: We aim to recruit 150 older adults with comorbid insomnia who have presented to community mental health services for depression. Eligible participants will be randomly allocated via block/cluster randomisation to one of three group therapy conditions: CBT-I, CBT-I-D, or PCG. Participants who receive CBT-I will only practice strategies designed to improve their sleep, whereas participants who receive CBT-I-D will practice additional strategies designed to also improve their mood. This trial will implement a mixed-methods design involving quantitative outcome measures and qualitative focus groups. The primary outcome measures are insomnia and depression severity, and secondary outcomes are anxiety, hopelessness, beliefs about sleep, comorbid sleep conditions, and health. Outcomes will be assessed at pre-intervention (week 0), post-intervention (week 8), and 3-month follow-up (week 20). Discussion: This CBT study protocol has been designed to address comorbid insomnia and depression for older adults receiving community mental health services. The proposed trial will determine whether CBT-I is more effective for older adults with comorbid insomnia and depression compared to a PCG. It will also establish whether an advanced form of CBT-I-D generates greater reductions in insomnia and depression severity compared to standard CBT-I. The results from the proposed trial are anticipated to have important clinical implications for older adults, researchers, therapists, and community mental health services. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN: 12615000067572 , Date Registered 12 December 2014. © 2015 Sadler et al.
Self-care interventions that reduce hospital readmissions in patients with heart failure; towards the identification of change agents
- 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
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- 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.
Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22
- 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
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- 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.
Ambulatory blood pressure may be designed as the primary efficacy outcome in clinical trials on renal denervation
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Letter , Journal article
- Relation: International Journal of Cardiology Vol. 176, no. 3 (2014), p. 1262-1263
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
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Dynamics of IL-4 and IL-13 expression in the airways of sheep following allergen challenge
- Authors: Liravi, Bahar , Piedrafita, David , Nguyen, Gary , Bischof, Robert
- Date: 2015
- Type: Text , Journal article
- Relation: BMC Pulmonary Medicine Vol. 15, no. 1 (2015), p. 1-11
- Full Text:
- Reviewed:
- Description:
Background: IL-4 and IL-13 play a critical yet poorly understood role in orchestrating the recruitment and activation of effector cells of the asthmatic response and driving the pathophysiology of allergic asthma. The house dust mite (HDM) sheep asthma model displays many features of the human condition and is an ideal model to further elucidate the involvement of these critical Th
2 cytokines. We hypothesized that airway exposure to HDM allergen would induce or elevate the expression profile of IL-4 and IL-13 during the allergic airway response in this large animal model of asthma. Methods: Bronchoalveolar lavage (BAL) samples were collected from saline-and house dust mite (HDM)-challenged lung lobes of sensitized sheep from 0 to 48h post-challenge. BAL cytokines (IL-4, IL-13, IL-6, IL-10, TNF-aα) were each measured by ELISA. IL-4 and IL-13 expression was assessed in BAL leukocytes by flow cytometry and in airway tissue sections by immunohistology. Results: IL-4 and IL-13 were increased in BAL samples following airway allergen challenge. HDM challenge resulted in a significant increase in BAL IL-4 levels at 4h compared to saline-challenged airways, while BAL IL-13 levels were elevated at all time-points after allergen challenge. IL-6 levels were maintained following HDM challenge but declined after saline challenge, while HDM administration resulted in an acute elevation in IL-10 at 4h but no change in TNF-aα levels over time. Lymphocytes were the main early source of IL-4, with IL-4 release by alveolar macrophages (AMs) prominent from 24h post-allergen challenge. IL-13 producing AMs were increased at 4 and 24h following HDM compared to saline challenge, and tissue staining provided evidence of IL-13 expression in airway epithelium as well as immune cells in airway tissue. Conclusion: In a sheep model of allergic asthma, airway inflammation is accompanied by the temporal release of key cytokines following allergen exposure that primarily reflects the Th2 -driven nature of the immune response in asthma. The present study demonstrates for the first time the involvement of IL-4 and IL-13 in a relevant large animal model of allergic airways disease. © 2015 Liravi et al.
It may be not suitable to perform renal denervation in renal arteries with significant stenosis
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Journal article , Letter
- Relation: International Journal of Cardiology Vol. 174, no. 3 (2014), p. 750
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
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Experimental and human evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin NGAL ) in the development of cardiac hypertrophy and heart failure
- Authors: Marques, Francine , Prestes, Priscilla , Byars, Sean , Ritchie, Scott , Wurtz, Peter , Patel, Sheila , Booth, Scott , Rana, Indrajeetsinh , Minoda, Yosuke , Berzins, Stuart , Curl, Claire , Bell, James , Wai, Bryan , Srivastava, Piyush , Kangas, Antti , Soininen, Pasi , Ruohonen, Saku , Kahonen, Mika , Lehtimaki, Terho , Raitoharju, Emma , Havulinna, Aki , Perola, Markus , Raitakari, Olli , Salomaa, Veikko , Ala-Korpela, Mika , Kettunen, Johannes , McGlynn, Maree , Kelly, Jason , Wlodek, Mary , Lewandowski, Paul , Delbridge, Lea , Burrell, Louise , Inouye, Michael , Harrap, Stephen , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article
- Relation: Journal of the American Heart Association Vol. 6, no. 6 (2017), p. 1-58
- Relation: http://purl.org/au-research/grants/nhmrc/1034371
- Full Text:
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- Description: Background-Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. Methods and Results-We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. Conclusions-Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure.
Limitations in current clinical trials on renal denervation
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Journal article , Letter
- Relation: International Journal of Cardiology Vol. 174, no. 1 (2014), p. 225
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
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:
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Renal nerves contribute to hypertension in Schlager BPH/2J mice
- 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:
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- 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.
It is urgent to investigate predictors of the response of blood pressure to renal denervation
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Journal article , Letter
- Relation: Canadian Journal of Cardiology Vol. 30, no. 4 (2014), p. 465.e7
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
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The efficacy of different modes of analgesia in postoperative pain management and early mobilization in postoperative cardiac surgical patients : A systematic review
- 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
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- 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.
Coronary artery disease : Why we should consider the Y chromosome
- Authors: Molina, Elsa , Clarence, Elyse , Ahmady, Farah , Chew, Guatsiew , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article , Review
- Relation: Heart Lung and Circulation Vol. 25, no. 8 (Aug 2016), p. 791-801
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
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- Description: Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality globally. In the last few years our understanding of the genetic and molecular mechanisms that promote CAD in individuals has increased with the advent of the genome era. This complex inflammatory disease has well-defined environmental risk factors. However, in the last 10 years, studies including genome-wide association studies (GWAS) have clearly demonstrated a genetic influence on CAD. Recently, studies on the human Y chromosome have also demonstrated that genetic variation within the male-specific region of the Y chromosome (MSY) could play a part in determining cardiovascular risk in men, confirming the notion that the increased risk for CAD in men cannot be fully explained through common CAD risk factors. Here, we review the literature about the pathophysiology of CAD, its potential causes and environmental risk factors known so far. Furthermore, we review the genetics of CAD, especially the latest discoveries regarding the implication of the Y chromosome, the most underexplored portion of the human genome to date, highlighting methods and difficulties arising in this research field, and discussing the importance of considering the Y chromosome in CAD research.
Bronchial thermoplasty reduces airway resistance
- Authors: Langton, David , Bennetts, Kim , Noble, Peter , Plummer, Virginia , Thien, Francis
- Date: 2020
- Type: Text , Journal article
- Relation: Respiratory Research Vol. 21, no. 1 (2020), p.
- Full Text:
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- Description: Background: The mechanism for symptomatic improvement after bronchial thermoplasty (BT) is unclear, since spirometry reveals little or no change. In this study, the effects of BT on airway resistance were examined using two independent techniques. Methods: Eighteen consecutive patients, with severe asthma (57.6 ± 14.2 years) were evaluated by spirometry and plethysmography at three time points: (i) baseline, (ii) left lung treated but right lung untreated and (iii) 6 weeks after both lungs were treated with BT. At each assessment, total and specific airway resistance (Raw, sRaw) were measured. High resolution CT scans were undertaken at the first two assessments, and measurements of lobar volume, airway volume and airway resistance were made. The Asthma Control Questionnaire (ACQ) was administered at each assessment. Results: The baseline ACQ score was 3.5 ± 0.9, and improved progressively to 1.8 ± 1.2 (p < 0.01). At baseline, severe airflow obstruction was observed, FEV1 44.8 ± 13.7% predicted, together with gas trapping, and elevated Raw at 342 ± 173%predicted. Following BT, significant improvements in Raw and sRaw were observed, as well as a reduction in Residual Volume, increase in Vital Capacity and no change in FEV1. The change in Raw correlated with the change in ACQ (r = 0.56, p < 0.05). CT scans demonstrated reduced airway volume at baseline, which correlated with the increased Raw determined by plethysmography (p = - 0.536, p = < 0.05). Following BT, the airway volume increased in the treated lung, and this was accompanied by a significant reduction in CT-determined local airway resistance. Conclusion: Symptomatic improvement after BT is mediated by increased airway volume and reduced airway resistance. © 2020 The Author(s).