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Find video protocols related to scientific articles indexed in Pubmed.
Prediction of Cardiovascular and All-Cause Mortality at 10 Years in the Hypertensive Aged Population.
Am. J. Hypertens.
PUBLISHED: 11-16-2014
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We have previously developed a score for predicting cardiovascular events in the intermediate term in an elderly hypertensive population. In this study, we aimed to extend this work to predict 10-year cardiovascular and all-cause mortality in the hypertensive aged population.
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'Neonatal' Nav1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour.
Hum. Mol. Genet.
PUBLISHED: 11-06-2014
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Developmentally regulated alternative splicing produces 'neonatal' and 'adult' isoforms of four Na(+) channels in human brain, NaV1.1, NaV1.2, NaV1.3 and NaV1.6. Heterologously expressed 'neonatal' NaV1.2 channels are less excitable than 'adult' channels; however, functional importance of this difference is unknown. We hypothesized that the 'neonatal' NaV1.2 may reduce neuronal excitability and have a seizure-protective role during early brain development. To test this hypothesis, we generated NaV1.2(adult) mice expressing only the 'adult' NaV1.2, and compared the firing properties of pyramidal cortical neurons, as well as seizure susceptibility, between the NaV1.2(adult) and wild-type (WT) mice at postnatal day 3 (P3), when the 'neonatal' isoform represents 65% of the WT NaV1.2. We show significant increases in action potential firing in NaV1.2(adult) neurons and in seizure susceptibility of NaV1.2(adult) mice, supporting our hypothesis. At postnatal day 15 (P15), when 17% of the WT NaV1.2 is 'neonatal', the firing properties of NaV1.2(adult) and WT neurons converged. However, inhibitory postsynaptic currents in NaV1.2(adult) neurons were larger and the expression level of Scn2a mRNA was 24% lower compared with the WT. The enhanced seizure susceptibility of the NaV1.2(adult) mice persisted into adult age. The adult NaV1.2(adult) mice also exhibited greater risk-taking behaviour. Overall, our data reveal a significant impact of 'neonatal' NaV1.2 on neuronal excitability, seizure susceptibility and behaviour and may contribute to our understanding of NaV1.2 roles in health and diseases such as epilepsy and autism.
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Amino-terminal-pro-B-type natriuretic peptide levels and low diastolic blood pressure: potential relevance to the diastolic J-curve.
J. Hypertens.
PUBLISHED: 10-03-2014
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There is debate whether the J-curve relationship between cardiac event risk and DBP is because of inherent cardiac risk or is a consequence of blood pressure (BP) lowering therapy.
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Small-molecule inhibitors of the pseudaminic Acid biosynthetic pathway: targeting motility as a key bacterial virulence factor.
Antimicrob. Agents Chemother.
PUBLISHED: 09-29-2014
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Helicobacter pylori is motile by means of polar flagella, and this motility has been shown to play a critical role in pathogenicity. The major structural flagellin proteins have been shown to be glycosylated with the nonulosonate sugar, pseudaminic acid (Pse). This glycan is unique to microorganisms, and the process of flagellin glycosylation is required for H. pylori flagellar assembly and consequent motility. As such, the Pse biosynthetic pathway offers considerable potential as an antivirulence drug target, especially since motility is required for H. pylori colonization and persistence in the host. This report describes screening the five Pse biosynthetic enzymes for small-molecule inhibitors using both high-throughput screening (HTS) and in silico (virtual screening [VS]) approaches. Using a 100,000-compound library, 1,773 hits that exhibited a 40% threshold inhibition at a 10 ?M concentration were identified by HTS. In addition, VS efforts using a 1.6-million compound library directed at two pathway enzymes identified 80 hits, 4 of which exhibited reasonable inhibition at a 10 ?M concentration in vitro. Further secondary screening which identified 320 unique molecular structures or validated hits was performed. Following kinetic studies and structure-activity relationship (SAR) analysis of selected inhibitors from our refined list of 320 compounds, we demonstrated that three inhibitors with 50% inhibitory concentrations (IC50s) of approximately 14 ?M, which belonged to a distinct chemical cluster, were able to penetrate the Gram-negative cell membrane and prevent formation of flagella.
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Comparison of Predictive Performance of Renal Function Estimation Equations for All-Cause and Cardiovascular Mortality in an Elderly Hypertensive Population.
Am. J. Hypertens.
PUBLISHED: 09-21-2014
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The Modifications of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are 2 equations commonly used to estimate glomerular filtration rate (eGFR). The predictive performance offered by these equations, particularly in relation to clinical outcomes in elderly hypertensive patients, is not clear.
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A review of valve surgery for rheumatic heart disease in Australia.
BMC Cardiovasc Disord
PUBLISHED: 08-02-2014
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Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects older non-Indigenous Australians and Aboriginal Australians and/or Torres Strait Islander peoples. Factors associated with the choice of treatment for advanced RHD remain variable and poorly understood.
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Acute risk change for cardiothoracic admissions to intensive care: A new measure of quality in cardiac surgery.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 07-22-2014
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Quality of cardiac surgical care may vary between institutions. Mortality is low and large numbers are required to discriminate between hospitals. Measures other than mortality may provide better comparisons.
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Prolonged effectiveness of coronary artery bypass surgery versus drug-eluting stents in diabetics with multi-vessel disease: an updated systematic review and meta-analysis.
Int. J. Cardiol.
PUBLISHED: 07-06-2014
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Currently, the appropriateness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) for patients with diabetes (DM) and multi-vessel disease (MVD) is uncertain due to limited evidence from few randomised controlled trials (RCTs). We aimed to compare the clinical effectiveness of CABG versus PCI-DES in DM-MVD patients using an evidence-based approach.
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Effect of dietary prebiotic supplementation on advanced glycation, insulin resistance and inflammatory biomarkers in adults with pre-diabetes: a study protocol for a double-blind placebo-controlled randomised crossover clinical trial.
BMC Endocr Disord
PUBLISHED: 06-30-2014
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Advanced glycation endproducts (AGEs) contribute to the development of vascular complications of diabetes and have been recently implicated in the pathogenesis of diabetes. Since AGEs are generated within foodstuffs upon food processing, it is increasingly recognised that the modern diet is replete with AGEs. AGEs are thought to stimulate chronic low-grade inflammation and promote oxidative stress and have been linked to the development of insulin resistance. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of type 2 diabetes in susceptible individuals. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host, but its effect on advanced glycation is unknown. The aim of this article is to describe the methodology of a double-blind placebo-controlled randomised crossover trial designed to determine the effect of 12 week consumption of a prebiotic dietary supplement on the advanced glycation pathway, insulin sensitivity and chronic low-grade inflammation in adults with pre-diabetes.
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Assessment of vitamin D and its association with cardiovascular disease risk factors in an adult migrant population: an audit of patient records at a Community Health Centre in Kensington, Melbourne, Australia.
BMC Cardiovasc Disord
PUBLISHED: 06-19-2014
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Vitamin D deficiency is a global public health problem associated with increased risk of cardio-metabolic diseases and osteoarthritis. Migrants with dark skin settled in temperate climates are at greater risk of both vitamin D deficiency and cardiovascular diseases. This study aims to identify the risk of vitamin D deficiency and associations with cardiovascular disease in a migrant population in Australia.
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Epilepsy, energy deficiency and new therapeutic approaches including diet.
Pharmacol. Ther.
PUBLISHED: 05-27-2014
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Metabolic dysfunction leading to epilepsy is well recognised. Dietary therapy, in particular the ketogenic diet, is now considered an effective option. Recent genetic studies have highlighted the central role that metabolism can play in setting seizure susceptibility. Here we discuss various metabolic disorders implicated in epilepsy focusing on energy deficiency due to genetic and environmental causes. We argue that low, uncompensated brain glucose levels can precipitate seizures. We will also explore mechanisms of disease and therapy in an attempt to identify common metabolic pathways involved in modulating seizure susceptibility. Finally, newer therapeutic approaches based on diet manipulation in the context of energy deficiency are discussed.
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Mapping somatosensory connectivity in adult mice using diffusion MRI tractography and super-resolution track density imaging.
Neuroimage
PUBLISHED: 04-20-2014
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In this study we combined ultra-high field diffusion MRI fiber tracking and super-resolution track density imaging (TDI) to map the relay locations and connectivity of the somatosensory pathway in paraformaldehyde fixed, C57Bl/6J mouse brains. Super-resolution TDI was used to achieve 20?m isotropic resolution to inform the 3D topography of the relay locations including thalamic barreloids and brainstem barrelettes, not described previously using MRI methodology. TDI-guided mapping results for thalamo-cortical connectivity were consistent with thalamo-cortical projections labeled using virus mediated fluorescent protein expression. Trigemino-thalamic TDI connectivity maps were concordant with results obtained using anterograde dye tracing from brainstem to thalamus. Importantly, TDI mapping overcame the constraint of tissue distortion observed in mechanically sectioned tissue, enabling 3D reconstruction and long-range connectivity data. In conclusion, our results showed that diffusion micro-imaging at ultra-high field MRI revealed the stereotypical pattern of somatosensory connectivity and is a valuable tool to complement histologic methods, achieving 3D spatial preservation of whole brain networks for characterization in mouse models of human disease.
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Reduced dendritic arborization and hyperexcitability of pyramidal neurons in a Scn1b-based model of Dravet syndrome.
Brain
PUBLISHED: 04-17-2014
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Epileptic encephalopathies, including Dravet syndrome, are severe treatment-resistant epilepsies with developmental regression. We examined a mouse model based on a human ?1 sodium channel subunit (Scn1b) mutation. Homozygous mutant mice shared phenotypic features and pharmaco-sensitivity with Dravet syndrome. Patch-clamp analysis showed that mutant subicular and layer 2/3 pyramidal neurons had increased action potential firing rates, presumably as a consequence of their increased input resistance. These changes were not seen in L5 or CA1 pyramidal neurons. This raised the concept of a regional seizure mechanism that was supported by data showing increased spontaneous synaptic activity in the subiculum but not CA1. Importantly, no changes in firing or synaptic properties of gamma-aminobutyric acidergic interneurons from mutant mice were observed, which is in contrast with Scn1a-based models of Dravet syndrome. Morphological analysis of subicular pyramidal neurons revealed reduced dendritic arborization. The antiepileptic drug retigabine, a K+ channel opener that reduces input resistance, dampened action potential firing and protected mutant mice from thermal seizures. These results suggest a novel mechanism of disease genesis in genetic epilepsy and demonstrate an effective mechanism-based treatment of the disease.
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A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk.
Eur J Prev Cardiol
PUBLISHED: 03-29-2014
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Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications.
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Predictors of health care use among patients with or at high risk of atherothrombotic disease: two-year follow-up data.
Int. J. Cardiol.
PUBLISHED: 03-24-2014
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Atherothrombotic diseases are the leading health problems in the world, both in terms of morbidity and mortality. This study aimed to identify and quantify the predictors of medication, hospital and outpatient service use among patients with or at high risk of atherothrombotic disease.
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Prolonged impact of home versus clinic-based management of chronic heart failure: extended follow-up of a pragmatic, multicentre randomized trial cohort.
Int. J. Cardiol.
PUBLISHED: 03-10-2014
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We compared the longer-term impact of the two most commonly applied forms of post-discharge management designed to minimize recurrent hospitalization and prolong survival in typically older patients with chronic heart failure (CHF).
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A propensity-score matched analysis on the impact of postoperative atrial fibrillation on the early and late outcomes after concomitant aortic valve replacement and coronary artery bypass graft surgery.
J Cardiovasc Med (Hagerstown)
PUBLISHED: 02-28-2014
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Postoperative atrial fibrillation (POAF) is a known complication of cardiac surgery. There is a paucity of data on the effects of POAF on short-term and long-term outcomes after concomitant aortic valve replacement and coronary artery bypass grafting (AVR-CABG ).
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KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine.
Ann. Neurol.
PUBLISHED: 02-21-2014
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Mutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of infancy with migrating focal seizures (EIMFS). More recently, a whole exome sequencing study of epileptic encephalopathies identified an additional de novo mutation in 1 proband with EIMFS. We aim to investigate the electrophysiological and pharmacological characteristics of hKCNT1 mutations and examine developmental expression levels.
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Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence.
J. Am. Soc. Nephrol.
PUBLISHED: 02-07-2014
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Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P<0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence.
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Impact of socioeconomic status and rurality on early outcomes and mid-term survival after CABG: insights from a multicentre registry.
Heart Lung Circ
PUBLISHED: 02-01-2014
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We examined whether socioeconomic status and rurality influenced outcomes after coronary surgery.
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Systolic blood pressure variability is an important predictor of cardiovascular outcomes in elderly hypertensive patients.
J. Hypertens.
PUBLISHED: 02-01-2014
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In hypertensive persons aged 60 years or below, visit-to-visit SBP variability is directly associated with cardiovascular events, especially stroke. It is unclear whether such a relationship exists for older persons. We investigated whether there is a relationship between visit-to-visit SBP variability and cardiovascular events in an elderly population, and identified the factors associated with increased SBP variability.
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The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration --improving the quality of cardiovascular care in the Asia Pacific region.
Int. J. Cardiol.
PUBLISHED: 02-01-2014
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Clinicians and other stakeholders recognize the need for clinical registries to monitor data in order to improve the outcome and quality of care in the delivery of medical interventions. The establishment of a collaboration across the Asia Pacific Region to inform on variations in patient and procedural characteristics and associated clinical outcomes would enable regional benchmarking of quality.
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AusSCORE II in predicting 30-day mortality after isolated coronary artery bypass grafting in Australia and New Zealand.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 01-29-2014
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To update the Australian System for Cardiac Operative Risk Evaluation (AusSCORE) model for operative estimation of 30-day mortality risk after isolated coronary artery bypass grafting in the Australian population.
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Follistatin promotes adipocyte differentiation, browning, and energy metabolism.
J. Lipid Res.
PUBLISHED: 01-17-2014
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Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-? superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1? was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells. Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism.
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Enhanced in vitro CA1 network activity in a sodium channel ?1(C121W) subunit model of genetic epilepsy.
Epilepsia
PUBLISHED: 01-15-2014
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A NaV ?1(C121W) mouse model of human genetic epilepsy has enhanced neuronal excitability and temperature sensitivity attributed to a decreased threshold for action potential firing in the axon initial segment. To investigate the network consequences of this neuronal dysfunction and to establish a genetic disease state model we developed an in vitro assay to investigate CA1 network properties and antiepileptic drug sensitivity.
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Development and validation of the Emergency Department Assessment of Chest pain Score and 2 h accelerated diagnostic protocol.
Emerg Med Australas
PUBLISHED: 01-15-2014
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Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED, saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol (ADP) that could safely increase the proportion of patients suitable for early discharge.
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HCN channelopathy and cardiac electrophysiologic dysfunction in genetic and acquired rat epilepsy models.
Epilepsia
PUBLISHED: 01-13-2014
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Evidence from animal and human studies indicates that epilepsy can affect cardiac function, although the molecular basis of this remains poorly understood. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate pacemaker activity and modulate cellular excitability in the brain and heart, with altered expression and function associated with epilepsy and cardiomyopathies. Whether HCN expression is altered in the heart in association with epilepsy has not been investigated previously. We studied cardiac electrophysiologic properties and HCN channel subunit expression in rat models of genetic generalized epilepsy (Genetic Absence Epilepsy Rats from Strasbourg, GAERS) and acquired temporal lobe epilepsy (post-status epilepticus SE). We hypothesized that the development of epilepsy is associated with altered cardiac electrophysiologic function and altered cardiac HCN channel expression.
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Impact of renal function in patients with multi-vessel coronary disease on long-term mortality following coronary artery bypass grafting compared with percutaneous coronary intervention.
Int. J. Cardiol.
PUBLISHED: 01-11-2014
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Comorbidities, such as diabetes, affect revascularization strategy for coronary disease. We sought to determine if the degree of renal impairment affected long-term mortality after percutaneous coronary intervention (PCI) compared to coronary artery bypass grafting (CABG) in patients with multi-vessel coronary disease (MVD).
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Cardiovascular medication use following percutaneous coronary intervention: the Australian experience.
Cardiovasc Ther
PUBLISHED: 01-08-2014
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Despite the guidelines, a "treatment gap" exists in the delivery of pharmacotherapy for secondary prevention. We aimed to analyze the trend in guideline-based medication usage following percutaneous coronary intervention (PCI) using the Melbourne Interventional Group (MIG) registry over a 6-year period (2005-2010).
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The effects of fungal volatile organic compounds on bone marrow stromal cells.
Can. J. Microbiol.
PUBLISHED: 01-08-2014
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Evidence has shown that individuals exposed to indoor toxic molds for extended periods of time have elevated risk of developing numerous respiratory illnesses. It is not clear at the cellular level what impact mold exposure has on the immune system. Herein, we show that 2 fungal volatiles (E)-2-octenal and oct-1-en-3-ol have cytotoxic effects on murine bone marrow stromal cells. To further analyze alterations to the cell, we evaluated the impact these volatile organic compounds have on membrane composition and hence fluidity. Both (E)-2-octenal and oct-1-en-3-ol exposure caused a shift to unsaturated fatty acids and lower cholesterol levels in the membrane. This indicates that the volatile organic compounds under investigation increased membrane fluidity. These vast changes to the cell membrane are known to contribute to the breakdown of normal cell function and possibly lead to death. Since bone marrow stromal cells are vital for the appropriate development and activation of immune cells, this study provides the foundation for understanding the mechanism at a cellular level for how mold exposure can lead to immune-related disease conditions.
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Predictors of mean arterial pressure morning rate of rise and power function in subjects undergoing ambulatory blood pressure recording.
PLoS ONE
PUBLISHED: 01-01-2014
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We determined clinical predictors of the rate of rise (RoR) in blood pressure in the morning as well as a novel measure of the power of the BP surge (BP(power)) derived from ambulatory blood pressure recordings.
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Short- and long-term survival in treated elderly hypertensive patients with or without diabetes: findings from the second Australian national blood pressure study.
Am. J. Hypertens.
PUBLISHED: 11-18-2013
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We sought to determine the incidence of newly diagnosed diabetes in treated elderly hypertensive patients and the prognostic impact of diabetes on long-term survival.
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Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials.
Br. J. Nutr.
PUBLISHED: 11-13-2013
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Complex relationships exist between the gut microflora and their human hosts. Emerging evidence suggests that bacterial dysbiosis within the colon may be involved in the pathogenesis of the metabolic syndrome, type 2 diabetes and CVD. The use of dietary prebiotic supplements to restore an optimal balance of intestinal flora may positively affect host metabolism, representing a potential treatment strategy for individuals with cardiometabolic disorders. The present review aimed to examine the current evidence supporting that dietary prebiotic supplementation in adults has beneficial effects on biochemical parameters associated with the development of metabolic abnormalities including obesity, glucose intolerance, dyslipidaemia, hepatic steatosis and low-grade chronic inflammation. Between January 2000 and September 2013, eight computer databases were searched for randomised controlled trials published in English. Human trials were included if at least one group received a dietary prebiotic intervention. In the present review, twenty-six randomised controlled trials involving 831 participants were included. Evidence indicated that dietary prebiotic supplementation increased self-reported feelings of satiety in healthy adults (standardised mean difference - 0·57, 95 % CI - 1·13, - 0·01). Prebiotic supplementation also significantly reduced postprandial glucose ( - 0·76, 95 % CI - 1·41, - 0·12) and insulin ( - 0·77, 95 % CI - 1·50, - 0·04) concentrations. The effects of dietary prebiotics on total energy intake, body weight, peptide YY and glucagon-like peptide-1 concentrations, gastric emptying times, insulin sensitivity, lipids, inflammatory markers and immune function were contradictory. Dietary prebiotic consumption was found to be associated with subjective improvements in satiety and reductions in postprandial glucose and insulin concentrations. Additional evidence is required before recommending prebiotic supplements to individuals with metabolic abnormalities. Large-scale trials of longer duration evaluating gut microbial growth and activity are required.
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Impact of Smoking Status on Outcomes after Concomitant Aortic Valve Replacement and Coronary Artery Bypass Graft Surgery.
Thorac Cardiovasc Surg
PUBLISHED: 10-25-2013
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Background There is a paucity of data on the impact of smoking status on outcomes after concomitant aortic valve replacement and coronary artery bypass graft (AVR-CABG) surgery.Methods Data obtained prospectively between June 2001 and December 2009 by the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program were retrospectively analyzed. Demographic and operative data were compared between patients who were nonsmokers, previous smokers, and current smokers using chi-square test and t-test. The independent impact of smoking status on 14 short-term complications and long-term mortality was determined using binary logistic and Cox regression, respectively.Results Concomitant AVR-CABG surgery was performed in 2,563 patients; smoking status was recorded in 2,558 (99.8%) patients. Of these, 1,052 (41.1%) patients had no previous smoking history, 1,345 (52.6%) patients were previous smokers, and 161 (6.3%) patients were current smokers. The 30-day mortality rate was 3.5% in nonsmokers, 4.1% in previous smokers, and 3.1% in current smokers (p = nonsignificant). The incidence of perioperative complications was similar in the three groups. The mean follow-up period for this study was 36 months (range, 0-105 months). After adjusting for differences in patient variables, the incidence of late mortality was higher in previous smokers (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.14-1.81; p = 0.002) compared with nonsmokers. A trend toward increased late mortality in current smokers was noted (HR, 1.34; 95% CI, 0.86-2.08; p = 0.201).Conclusion Smoking is not associated with adverse outcomes after concomitant AVR-CABG surgery. Smoking status should not, therefore, preclude these patients from undergoing this procedure. Given the adverse effect of smoking on overall cardiovascular morbidity and mortality and late postoperative mortality, patients should be encouraged to quit smoking.
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Functional analysis of SleC from Clostridium difficile: an essential lytic transglycosylase involved in spore germination.
Microbiology (Reading, Engl.)
PUBLISHED: 10-18-2013
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Clostridium difficile is the most common cause of enteric disease and presents a major burden on healthcare systems globally due in part to the observed rapid rise in antibiotic resistance. The ability of C. difficile to form endospores is a key feature in the organisms pathogenesis and transmission, and contributes greatly to its resilient nature. Endospores are highly resistant to disinfection, allowing them to persist on hospital surfaces. In order for the organism to cause disease, the spores must germinate and revert to a vegetative form. While spore germination in Bacillus spp. is well understood, very little is known about this process in Clostridia. Here we report the characterization of SleC (CD0551) from C. difficile 630. Bioinformatic analysis of SleC indicated a multi-domained protein possessing a peptidoglycan-binding (PGB) domain, a SpoIID/LytB domain and an undefined N-terminal region. We have confirmed that SleC is an exo-acting lytic transglycosylase with the catalytic activity localized to the N-terminal region. Additionally, we have shown that both the N-terminal catalytic domain and the C-terminal PGB domain require muramyl-?-lactam for substrate binding. As with carbohydrate-binding modules from cellulases and xylanases, the PGB domain may be responsible for increasing the processivity of SleC by concentrating the enzyme at the surface of the substrate.
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Overview of pharmacoeconomic modelling methods.
Br J Clin Pharmacol
PUBLISHED: 09-21-2013
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In the current climate of burgeoning health care costs, pharmacoeconomics is becoming increasingly important, but knowledge about pharmacoeconomic methods is limited among most clinicians. This review provides an introduction to, and overview of, common methods used in pharmacoeconomic modelling: decision analysis, Markov modelling, discounting and uncertainty analyses via Monte Carlo simulation. It will conclude with a suggested approach to reading and appraising published pharmacoeconomic analyses.
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Spike-and-wave discharge mediated reduction in hippocampal HCN1 channel function associates with learning deficits in a genetic mouse model of epilepsy.
Neurobiol. Dis.
PUBLISHED: 09-13-2013
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The GABAA?2(R43Q) mouse is an established model of absence epilepsy displaying spontaneous spike-and-wave discharges (SWD) and associated behavioral arrest. Absence epilepsy typically results from cortico-thalamic networks. Nevertheless, there is increasing evidence for changes in hippocampal metabolism and electrical behavior, consistent with a link between absence seizures and hippocampus-related co-morbidities. Hyperpolarization-activated-cyclic-nucleotide-gated (HCN) channels are known to be transcriptionally regulated in a number of seizure models. Here we investigate the expression and function of these channels in the hippocampus of the genetic epilepsy model. A reduction in HCN1, but not HCN2 transcript, was observed in GABAA?2(R43Q) mice relative to their littermate controls. In contrast, no change in HCN1 transcript was noted at an age prior to seizure expression or in a SWD-free model in which the R43Q mutation has been crossed into a seizure-resistant genetic background. Whole-cell recordings from CA1 pyramidal neurons confirm a reduction in Ih in the GABAA?2(R43Q) mouse. Further, a left-shift in half-activation of the Ih conductance-voltage relationship is consistent with a reduction in HCN1 with no change in HCN2 channel expression. Behavioral analysis using the Morris water maze indicates that GABAA?2(R43Q) mice are unable to learn as effectively as their wildtype littermates suggesting a deficit in hippocampal-based learning. SWD-free mice harboring the R43Q mutation had no learning deficit. We conclude that SWDs reduce hippocampal HCN1 expression and function, and that the reduction associates with a spatial learning deficit.
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Smoking and primary total hip or knee replacement due to osteoarthritis in 54,288 elderly men and women.
BMC Musculoskelet Disord
PUBLISHED: 09-02-2013
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The reported association of smoking with risk of undergoing a total joint replacement (TJR) due to osteoarthritis (OA) is not consistent. We evaluated the independent association between smoking and primary TJR in a large cohort.
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Impact of left ventricular dysfunction on early and late outcomes in patients undergoing concomitant aortic valve replacement and coronary artery bypass graft surgery.
Cardiol J
PUBLISHED: 07-26-2013
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An increasing proportion of patients present for concomitant aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) with left ventricular (LV) dysfunction. The aim of this study was to evaluate the early outcomes and late survival of patients with different degrees of LV function undergoing concomitant AVR and CABG.
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Impact of smoking status on early and late outcomes after isolated aortic valve replacement surgery.
J. Heart Valve Dis.
PUBLISHED: 06-27-2013
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Currently, insufficient data exist relating to the impact of smoking status on outcomes after isolated aortic valve replacement (AVR) surgery.
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Acute effect of carbamazepine on corticothalamic 5-9-Hz and thalamocortical spindle (10-16-Hz) oscillations in the rat.
Eur. J. Neurosci.
PUBLISHED: 06-19-2013
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A major side effect of carbamazepine (CBZ), a drug used to treat neurological and neuropsychiatric disorders, is drowsiness, a state characterized by increased slow-wave oscillations with the emergence of sleep spindles in the electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular recordings in freely moving or lightly anesthetized rats to explore the impact of CBZ within the intact corticothalamic (CT)-thalamocortical (TC) network, more specifically on CT 5-9-Hz and TC spindle (10-16-Hz) oscillations. Two to three successive 5-9-Hz waves were followed by a spindle in the cortical EEG. A single systemic injection of CBZ (20 mg/kg) induced a significant increase in the power of EEG 5-9-Hz oscillations and spindles. Intracellular recordings of glutamatergic TC neurons revealed 5-9-Hz depolarizing wave-hyperpolarizing wave sequences prolonged by robust, rhythmic spindle-frequency hyperpolarizing waves. This hybrid sequence occurred during a slow hyperpolarizing trough, and was at least 10 times more frequent under the CBZ condition than under the control condition. The hyperpolarizing waves reversed at approximately -70 mV, and became depolarizing when recorded with KCl-filled intracellular micropipettes, indicating that they were GABAA receptor-mediated potentials. In neurons of the GABAergic thalamic reticular nucleus, the principal source of TC GABAergic inputs, CBZ augmented both the number and the duration of sequences of rhythmic spindle-frequency bursts of action potentials. This indicates that these GABAergic neurons are responsible for the generation of at least the spindle-frequency hyperpolarizing waves in TC neurons. In conclusion, CBZ potentiates GABAA receptor-mediated TC spindle oscillations. Furthermore, we propose that CT 5-9-Hz waves can trigger TC spindles.
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Prediction of acute kidney injury within 30 days of cardiac surgery.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 05-27-2013
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To predict acute kidney injury after cardiac surgery.
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Low glycaemic index diet reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy.
Epilepsy Res.
PUBLISHED: 05-13-2013
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Clinical evidence suggests that low glycaemic index diets are effective at reducing seizure frequency potentially through the stabilization of blood glucose levels. Here we investigate if diets containing carbohydrates with varying glycaemic index (GI) can modulate seizure susceptibility in a mouse model of generalized epilepsy.
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Effect of lipid exposure on graft patency and clinical outcomes: arteries and veins are different.
Eur J Cardiothorac Surg
PUBLISHED: 05-12-2013
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OBJECTIVES: We evaluated the influence of lipid exposure upon conduit patency in long-term follow-up after primary CABG. METHODS: From a prospectively compiled database, we identified 1207 grafts (436 SV and 771 mixed arterial grafts) among 413 CABG patients with 9.4 ± 2.4 years of follow-up (range 3-13). Surveillance angiography was performed as part of a randomized trial. All available lipid assays were collected from pathology laboratories, and from these, mean annualized lipid exposure was calculated for total cholesterol, HDL, LDL and triglycerides. Angiographical and clinical data were analysed against lipid exposure. Graft failure was defined as occlusion, string sign or >80% stenosis. RESULTS: Six thousand and seventy-seven lipid measurements were obtained, and there were 154 failed grafts. Three hundred and eleven patients received at least one vein graft, and all 413 patients received at least one arterial graft. Overall, only HDL levels were inversely correlated with graft failure, with total cholesterol and LDL showing no associations in a mixed pool of arterial and venous grafts. To assess whether total/LDL cholesterol had no effect or were exerting competing effects in arteries and veins, separate multivariate analyses were performed. Venous graft failure was associated with increased total cholesterol/HDL (P = 0.006) and LDL/HDL (P = 0.032). By contrast, elevated total cholesterol was correlated with a reduced risk of arterial graft failure (OR for graft failure 0.705, P = 0.023) with increasing LDL cholesterol following a similar trend (OR for graft failure 0.729, P = 0.051). CONCLUSION: Sub-fractions of dyslipidaemia known to be risk factors for native vessel disease appear to similarly influence vein grafts. Arterial conduits are at least more resistant to the effects of high lipid exposure, and appear to be protective. These results favour the use of arterial grafts in patients with poorly controlled dyslipidaemia.
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The Impact of Lost Therapeutic Benefit (LTB) in High-Risk Hypertensive Patients: 2-Year Follow-Up Data from the Australian REACH Registry.
Cardiovasc Ther
PUBLISHED: 04-16-2013
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The aim of the study is to determine the extent of lost therapeutic benefit (LTB) in the hypertensive patients, and to determine the relationship between the presence of LTB and clinical outcomes.
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Training surgeon status is not associated with an increased risk of early or late mortality after isolated aortic valve replacement surgery.
Cardiol J
PUBLISHED: 04-14-2013
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Few studies have addressed the effect of "trainee surgeon" status on outcomes after isolated aortic valve replacement (AVR).
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Predicting the impact of polypill use in a metabolic syndrome population: an effectiveness and cost-effectiveness analysis.
Am J Cardiovasc Drugs
PUBLISHED: 03-28-2013
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Individuals with metabolic syndrome (MetS) are at increased risk of cardiovascular disease (CVD), often requiring combination drug therapy for control of risk factors and subsequent risk reduction. This study aims to compare the long-term effectiveness and cost effectiveness of the polypill (a multi-component tablet), and its components (alone or in combination), in a MetS population.
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Does the addition of a radial artery graft improve survival after higher risk coronary artery bypass grafting? A propensity-score analysis of a multicentre database.
Eur J Cardiothorac Surg
PUBLISHED: 03-18-2013
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The use of the radial artery as a second arterial graft during coronary surgery has grown in popularity due to high patency and low harvest site complication rates. We sought to assess whether higher risk patients derive prognostic benefit.
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Transfusion practice varies widely in cardiac surgery: Results from a national registry.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 03-17-2013
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Evidence is accumulating of adverse outcomes associated with transfusion of blood components. If there are differences in perioperative transfusion rates in cardiac surgery, and what hospital factors may contribute, requires further investigation.
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NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular dysfunction: Results of the SCReening Evaluation of the Evolution of New Heart Failure Study (SCREEN-HF).
Int. J. Cardiol.
PUBLISHED: 03-10-2013
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We assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP).
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Health-risk factors and the prevalence of hypertension: cross-sectional findings from a national cohort of 87,143 Thai Open University students.
Glob J Health Sci
PUBLISHED: 03-10-2013
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Thailand is undergoing a health-risk transition which increases chronic diseases, particularly hypertension, as a result of a rapid transition from a developing to a developed country. This study analyzes the effect of health-risk factors such as demography, socioeconomic status (SES) and body mass index (BMI) on the prevalence of hypertension.
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Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy.
Neurology
PUBLISHED: 03-06-2013
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The human ?-aminobutyric acid type A (GABAA)?2R43Q (R43Q) mutation is associated with genetic epilepsy with febrile seizures. R43Q mice in the C57Bl/6J background do not display spontaneous seizures, but are significantly more susceptible to hyperthermic seizures, providing a model with enhanced seizure susceptibility without the confounding influence of ongoing epileptic activity. Because of GABAs role in brain development, we sought to determine whether the R43Q mutation alters brain structure before the appearance of seizures.
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Multiple molecular mechanisms for a single GABAA mutation in epilepsy.
Neurology
PUBLISHED: 02-13-2013
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To understand the molecular basis and differential penetrance of febrile seizures and absence seizures in patients with the ?2(R43Q) GABA receptor mutation.
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Outcomes and excess costs among patients with cardiovascular disease.
Heart Lung Circ
PUBLISHED: 02-10-2013
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To report on two-year cardiovascular (CV) event rates and quantify the cost of cardiovascular disease using the Australian Reduction of Atherothrombosis for Continued Health (REACH) registry.
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Effect of ramipril on walking times and quality of life among patients with peripheral artery disease and intermittent claudication: a randomized controlled trial.
JAMA
PUBLISHED: 02-07-2013
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Approximately one-third of patients with peripheral artery disease experience intermittent claudication, with consequent loss of quality of life.
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Patient preferences and willingness-to-pay for a home or clinic based program of chronic heart failure management: findings from the Which? trial.
PLoS ONE
PUBLISHED: 02-04-2013
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Beyond examining their overall cost-effectiveness and mechanisms of effect, it is important to understand patient preferences for the delivery of different modes of chronic heart failure management programs (CHF-MPs). We elicited patient preferences around the characteristics and willingness-to-pay (WTP) for a clinic or home-based CHF-MP.
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An unusual cause of severe persistent neutropenia in a child with nephrotic syndrome.
BMJ Case Rep
PUBLISHED: 02-01-2013
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A 5-year-old boy presented with neutropenia 9 weeks following the administration of rituximab for management of his steroid-dependent nephrotic syndrome. Extensive investigations failed to identify any underlying cause. In keeping with adult reports, rituximab was thought to be the likely cause for this late-onset neutropenia (LOP). He was treated successfully with granulocyte-colony-stimulating factor. Patients treated with rituximab need to be carefully monitored for LOP.
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Cardiovascular readmissions and excess costs following percutaneous coronary intervention in patients with chronic kidney disease: data from a large multi-centre Australian registry.
Int. J. Cardiol.
PUBLISHED: 01-29-2013
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Chronic kidney disease (CKD) is a well-established risk factor for adverse events in patients undergoing percutaneous coronary intervention (PCI). However, few data exists on the subsequent healthcare resource use and related incremental costs in this patient subgroup. The present study compares the rates of cardiac-related hospitalisations and the associated direct costs, post-PCI in patients with and without CKD.
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Interventions for impaired bladders in paediatric renal transplant recipients with lower urinary tract dysfunction.
Transpl. Int.
PUBLISHED: 01-25-2013
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Dysfunctional bladders in paediatric patients were thought to be a contraindication for renal transplantation, but advances in surgical techniques have meant that surgical correction can allow safe transplantation. This study compares the outcomes of renal transplantation for different interventions, and the timing of such interventions, in relation to transplantation. We identified all paediatric renal transplant recipients with LUTD that received intervention for their impaired bladders at two hospitals between 2002 and 2010. Outcome measures included patient and graft survival, perioperative complications, UTI incidence, acute rejection episodes and serum creatinine levels. A total of 288 allografts were transplanted, 77 were in 75 children with LUTD, of which 46 received intervention. Patient survival was 100% in the intervention group and 97% in the nonintervention group (P = 0.815). Death-censored graft survival was 96% and 100% respectively (P = 0.688). In the groups receiving intervention pretransplant or post-transplant, graft survival rates were 95% and 100% respectively (P = 0.476). The follow-up serum creatinine levels were higher in the pretransplant intervention group (P < 0.001). Interventions for dysfunctional bladders can be performed safely in paediatric renal transplant recipients. The mode of intervention and timing of intervention, in relation to transplant, do not influence outcomes if guided by careful assessment and investigation.
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Perturbations in cortical development and neuronal network excitability arising from prenatal exposure to benzodiazepines in mice.
Eur. J. Neurosci.
PUBLISHED: 01-21-2013
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During brain development, many factors influence the assembly and final positioning of cortical neurons, and this process is essential for proper circuit formation and normal brain function. Among many important extrinsic factors that guide the maturation of embryonic cortical neurons, the secreted neurotransmitter GABA has been proposed to influence both their migratory behaviour and their terminal differentiation. The full extent of the short-term and long-term changes in brain patterning and function caused by modulators of the GABA system is not known. In this study, we specifically investigated whether diazepam, a commonly used benzodiazepine that modulates the GABAA receptor, alters neuronal positioning in vivo, and whether this can lead to lasting effects on brain function. We found that fetal exposure to diazepam did not change cell positioning within the embryonic day (E)14.5 mouse cerebral cortex, but significantly altered neuron positioning within the E18.5 cortex. In adult mice, diazepam treatment affected the distribution of cortical interneurons that express parvalbumin or calretinin, and also led to a decrease in the numbers of calretinin-expressing interneurons. In addition, we observed that neonatal exposure to diazepam altered the sensitivity of mice to a proconvulsant challenge. Therefore, exposure of the fetal brain to benzodiazepines has consequences for the positioning of neurons and cortical network excitability.
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Physically disconnected non-diffusible cell-to-cell communication between neuroblastoma SH-SY5Y and DRG primary sensory neurons.
Am J Transl Res
PUBLISHED: 01-21-2013
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Cell-cell communication occurs via a variety of mechanisms, including long distances (hormonal), short distances (paracrine and synaptic) or direct coupling via gap junctions, antigen presentation, or ligand-receptor interactions. We evaluated the possibility of neuro-hormonal independent, non-diffusible, physically disconnected pathways for cell-cell communication using dorsal root ganglion (DRG) neurons.
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N-terminal B-type natriuretic peptide and the association with left ventricular diastolic function in a population at high risk of incident heart failure: results of the SCReening Evaluationof the Evolution of New-Heart Failure Study (SCREEN-HF).
Eur. J. Heart Fail.
PUBLISHED: 01-20-2013
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Impaired diastolic function is associated with increased morbidity and mortality, but antecedents and predictors of progression to heart failure (HF) are not well understood. We examined associations between NT-proBNP, HF risk factors, and diastolic function in a population at high risk for incident HF.
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The demographic characteristics of children with chronic kidney disease stages 3-5 in South East England over a 5-year period.
Arch. Dis. Child.
PUBLISHED: 01-12-2013
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To analyse the demographics of children with moderate to severe chronic kidney disease (CKD) stages 3-5 over a 5-year period for the population of South East England.
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Preoperative atrial fibrillation is an independent risk factor for mid-term mortality after concomitant aortic valve replacement and coronary artery bypass graft surgery.
Interact Cardiovasc Thorac Surg
PUBLISHED: 01-03-2013
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Preoperative atrial fibrillation (PAF) has been associated with poorer early and mid-term outcomes after isolated valvular or coronary artery bypass graft surgery. Few studies, however, have evaluated the impact of PAF on early and mid-term outcomes after concomitant aortic valve replacement and coronary aortic bypass graft (AVR-CABG) surgery.
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Health risk factors and the incidence of hypertension: 4-year prospective findings from a national cohort of 60 569 Thai Open University students.
BMJ Open
PUBLISHED: 01-01-2013
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This study evaluates the impact of a number of demographic, biological, behavioural and lifestyle health risk factors on the incidence of hypertension in Thailand over a 4-year period.
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Sex differences in outcomes following isolated coronary artery bypass graft surgery in Australian patients: analysis of the Australasian Society of Cardiac and Thoracic Surgeons cardiac surgery database.
Eur J Cardiothorac Surg
PUBLISHED: 11-11-2011
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Women undergoing isolated coronary artery bypass graft (CABG) surgery have been previously shown to be at an independently increased risk for post-operative morbidity and mortality. The current study evaluates the impact of sex as an independent risk factor for early and late morbidity and mortality following isolated CABG surgery.
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A score for the prediction of cardiovascular events in the hypertensive aged.
Am. J. Hypertens.
PUBLISHED: 10-20-2011
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With few exceptions, tools used to estimate cardiovascular disease (CVD) risk in those without prior events are based mainly on data from middle-aged subjects. Given the ever increasing number of older people, many with hypertension, a risk score relevant to this group is warranted. Our aim was to develop a cardiovascular risk equation suitable for risk prediction in elderly, hypertensive populations.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.