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Showing 701–720 of 2058 publications.
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Su, Qian Peter; Ju, Lining ArnoldThe focus of the cell biology field is now shifting from characterizing cellular activities to organelle and molecular behaviors. This process accompanies the development of new biophysical visualization techniques that offer high spatial and temporal resolutions with ultra-sensitivity and low cell toxicity. They allow the biology research community to observe dynamic behaviors from scales of single molecules, organelles, cells to organoids, and even live animal tissues. In this review, we summarize these biophysical techniques into two major classes: the mechanical nanotools like dynamic force spectroscopy (DFS) and the optical nanotools like single-molecule and super-resolution microscopy. We also discuss their applications in elucidating molecular dynamics and functionally mapping of interactions between inter-cellular networks and intra-cellular components, which is key to understanding cellular processes such as adhesion, trafficking, inheritance, and division. 2018, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature.
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Nasir-Ahmad, Subha; Cordina, Rachael Louise; Liew, Gerald; McCluskey, Peter Joseph; Celermajer, David S.In recent years, there has been a rise in the number patients with CHD surviving into adulthood. Many have complications related to their CHD or its treatments, outside the heart, including ocular abnormalities. The objective of this review is to highlight the ocular abnormalities that occur in adults with CHD, either from their condition or related to the common drugs prescribed to manage it. In particular, we reviewed the effects of cyanosis, coarctation of the aorta, endocarditis, and the side effects of Sildenafil and Amiodarone. A change in the retinal vasculature is a common observation with cyanosis or coarctation of the aorta. Occlusion of the retinal vessels may also be observed in cyanotic patients, as well as those with infectious endocarditis. Sildenafil has established ocular side effects; here they are explored in the context of therapy for pulmonary hypertension. Similarly, Amiodarone has established ocular risks, which are summarised. The high prevalence of ocular consequences in adult CHD patients reinforces the need for knowledge of the risks involved and for frequent ophthalmological screening where appropriate. Cambridge University Press 2018.
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Maller, Jerome Joseph; Broadhouse, Kathryn M.; Rush, Augustus John; Gordon, Evian; Koslow, Stephen H.; Grieve, Stuart M.Studies of patients with major depressive disorder (MDD) have consistently reported reduced hippocampal volumes; however, the exact pattern of these volume changes in specific anatomical subfields and their functional significance is unclear. We sought to clarify the relationship between hippocampal tail volumes and (i) a diagnosis of MDD, and (ii) clinical remission to anti-depressant medications (ADMs). Outpatients with nonpsychotic MDD (n=202) based on DSM-IV criteria and a 17-item Hamilton Rating Scale for Depression (HRSD<inf>17</inf>) score ?16 underwent pretreatment magnetic resonance imaging as part of the international Study to Predict Optimized Treatment for Depression (iSPOT-D). Gender-matched healthy controls (n=68) also underwent MRI scanning. An automated pipeline was used to objectively measure hippocampal subfield and whole brain volumes. Remission was defined as an HRSD<inf>17</inf> of ?7 following 8 weeks of randomized open-label treatment ADMs: escitalopram, sertraline or venlafaxine-extended release. After controlling for age and total brain volume, hippocampal tail volume was larger in the MDD cohort compared to control subjects. Larger hippocampal tail volume was positively related to clinical remission, independent of total hippocampal volume, total brain volume and age. These data provide convergent evidence of the importance of the hippocampus in the development or treatment of MDD. Hippocampal tail volume is proposed as a potentially useful biomarker of sensitivity to ADM treatment. 2018, Springer Nature Limited.
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Freedman, Ben Ben[No abstract available]
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Akhavan, Behnam; Michl, Thomas Danny; Giles, Carla; Kit Ho, Kitty Ka; Martin, Lewis J.; Sharifahmadian, Omid; Wise, Steven G.; Coad, Bryan R.; Kumar, Naresh Sampath; Griesser, Hans J.; Bilek, Marcela M.M.In the oral cavity, dental implants are exposed to an environment rich in various microbes that can produce infectious biofilms on the implant surface. Here we report the development of two distinct antimicrobial coatings that prevent biofilm formation by fungi or bacteria. The antimicrobial peptides Mel4 and caspofungin were immobilized on titanium surfaces through reactions with radicals embedded within a mechanically robust, ion-assisted plasma polymerized (PP) film. The immobilization does not require additional chemical reagents and is achieved by simply incubating the surfaces at room temperature in a buffer solution containing the antimicrobial agent. The antibiotic-functionalized surfaces were rigorously washed with hot sodium dodecyl sulphate (SDS) to remove physisorbed molecules, and analyzed by time of flight secondary ion mass spectrometry (ToF-SIMS), which revealed characteristic fragments of the peptides and provided strong evidence for the covalent nature of the binding between the molecules and the PP coating. Both Candida albicans and Staphylococcus aureus pathogens were significantly inhibited in their ability to colonize the surfaces and form biofilms. Our findings suggest that antimicrobial surfaces fabricated using ion-assisted plasma polymerization have great potential for coatings on biomedical devices where activity against fungal and bacterial pathogens is required. 2018 Elsevier Ltd
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Ngo, Linh Thi Hai; Vu, Van Ba; Nguyen, Huu Cong; Le, Tien Dung; Hoang, Trung Kien; Freedman, Ben Ben; Lowres, NicoleIntroduction Atrial fibrillation (AF) developing after cardiac surgery is the most common postoperative complication with an incidence up to 50%. The presence of postoperative AF is associated with significant morbidity, mortality and economic burden. However, in Vietnam, data on AF postcardiac surgery are limited, in part due to a shortage of screening equipment. This project aims to identify the incidence, risk factors and postoperative complications of new-onset postoperative AF after cardiac surgery, and the feasibility of introducing a novel screening strategy using the combination of two portable devices to detect AF. Methods and analysis This is a feasibility study examining patients who are (1) ?18 years old; (2) undergoing coronary artery bypass graft and/or valve surgery and (3) in normal sinus rhythm prior to their operation. Patients with congenital heart disease, a prior history of AF or those who require a pacemaker after surgery will be excluded. All patients will be followed up for the duration of their hospitalisation. The screening strategy will include monitoring the continuous ECG tracing in the intensive care unit, and if AF is suspected, a 30 s lead-1 ECG will be recorded using the smartphone-based AliveCor Kardia Mobile. On the postoperative wards, blood pressure will be measured three times daily using a modified blood pressure device (Microlife BP200 Afib): and if AF is suspected a 30 s ECG will be recorded using the AliveCor Kardia Mobile. A 12-lead ECG may be ordered subsequently if clinically indicated. The primary outcome is the incidence of postoperative AF. Secondary outcomes include establishing the risk factors and complications associated with postoperative AF; and the barriers and facilitators of the screening strategy. Ethics and dissemination Ethics approval was granted by Scientific Board of Cardiovascular Centre, E Hospital on 28 September, 2017. Study results will be disseminated through local and international conferences and peer-reviewed publications. Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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Bonnitcha, Paul D.; Grieve, Stuart M.; Figtree, Gemma A.Tissue hypoxia is a key feature of many important causes of morbidity and mortality. In pathologies such as stroke, peripheral vascular disease and ischaemic heart disease, hypoxia is largely a consequence of low blood flow induced ischaemia, hence perfusion imaging is often used as a surrogate for hypoxia to guide clinical diagnosis and treatment. Importantly, ischaemia and hypoxia are not synonymous conditions as it is not universally true that well perfused tissues are normoxic or that poorly perfused tissues are hypoxic. In pathologies such as cancer, for instance, perfusion imaging and oxygen concentration are less well correlated, and oxygen concentration is independently correlated to radiotherapy response and overall treatment outcomes. In addition, the progression of many diseases is intricately related to maladaptive responses to the hypoxia itself. Thus there is potentially great clinical and scientific utility in direct measurements of tissue oxygenation. Despite this, imaging assessment of hypoxia in patients is rarely performed in clinical settings. This review summarises some of the current methods used to clinically evaluate hypoxia, the barriers to the routine use of these methods and the newer agents and techniques being explored for the assessment of hypoxia in pathological processes. 2018 Elsevier Inc.
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Cholan, Pradeep Manuneedhi; Cartland, Si; Dang, Lei; Rayner, Benjamin Saul; Patel, Sanjay; Thomas, Shane R.; Kavurma, Mary M.The vascular endothelium is critical for maintenance of cardiovascular homeostasis. Endothelial dysfunction is a key event of atherosclerosis, with oxidative stress mediated by reactive oxygen species (ROS) playing a major role. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is increasingly recognised to play a protective role in atherosclerosis, however the molecular mechanisms by which it exerts its beneficial effects are unclear. Here we examined if TRAIL could attenuate vascular oxidative stress and improve endothelial cell (EC) function. In coronary artery disease patients, plasma TRAIL levels were significantly reduced compared to healthy individuals, and negatively correlated with the levels of circulating 8-iso Prostaglandin F<inf>2?</inf>, a marker of in vivo oxidative stress. In vivo, high-fat fed, atherosclerotic Trail-/-Apoe-/- mice exhibited a significant impairment in endothelial-dependent vasorelaxation, which correlated with increased vascular ROS and 4-hydroxynonenal compared to Apoe-/- mice. Endothelial permeability measured by Evan's blue dye extravasation was increased in several organs of Trail-/- mice compared to wild-type mice, which correlated with a decrease in VE-cadherin expression. In vitro in ECs, angiotensin II (AngII)-induced ROS generation involving the mitochondria, NADPH oxidase-4 (NOX-4) and eNOS, was inhibited by pre-treatment with TRAIL. Furthermore, AngII-augmented VCAM-1 expression and monocyte adhesion to ECs was inhibited by TRAIL. Finally, AngII reduced VE-cadherin expression and redistributed this protein, all of which was brought back to baseline by TRAIL pre-treatment. These findings demonstrate for the first time that TRAIL protects against several forms of endothelial dysfunction involving its ability to control EC ROS generation. Understanding the role TRAIL plays in normal physiology and disease, may lead to potential new therapies to improve endothelial function and atherosclerosis. 2018 Elsevier Inc.
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Callaghan, Fraser Maurice; Grieve, Stuart M.Wall shear stress (WSS) plays a governing role in vascular remodeling and a pathogenic role in vessel wall diseases. However, little is known of the normal WSS patterns in the aorta as there is currently no practical means to routinely measure WSS and no normal ranges derived from population data exist. WSS measurements were made on the aorta of 224 subjects with normal anatomy using four-dimensional flow MRI with multiple encoding velocities and an optimized postprocessing routine. The spatial and temporal variation in WSS and oscillatory shear index was analyzed using a flat map representation of the unfolded aorta. The influence of aortic shape and velocity on WSS was evaluated using regression analysis. WSS in the thoracic aorta is dominated by axial flow. Average peak systolic WSS was 1.79 0.71 Pa in the aortic arch and was significantly higher at 2.23 1.04 Pa in the descending aorta, with a strong negative correlation with advancing age. The spatial distribution of WSS is highly heterogeneous, with a localized region of elevated WSS along the length of the anterior wall seen across all individuals. Our data demonstrate that accurate four-dimensional flow-derived WSS measurement is feasible, and we further provide a standardized parametric approach for presentation and analysis. We present a normal range for WSS across the lifespan, demonstrating a decrease in WSS with advancing age as well as illustrating the high degree of spatial and temporal variation. NEW & NOTEWORTHY With the use of four-dimensional flow MRI and postprocessing, accurate direct measurement of wall shear stress (WSS) was performed in a population of normal thoracic aortas (n = 224). WSS was higher in the descending aorta compared with the aortic arch and decreased with age. A heterogeneous pattern of elevated WSS along the length of the aorta anterior wall was consistent across the population. This work provides normal data across the adult age range, permitting comparison with pathology. 2018 American Physiological Society. All rights reserved.
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Orchard, Jessica Joan; Lowres, Nicole; Neubeck, Lis; Freedman, Ben Ben[No abstract available]
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Callaghan, Fraser Maurice; Maller, Jerome Joseph; Welton, Thomas; Middione, Matthew J.; Shankaranarayanan, Ajit; Grieve, Stuart M.Diffusion MRI (dMRI) tractography is a uniquely powerful tool capable of demonstrating structural brain network abnormalities across a range of psychiatric disorders; however, it is not currently clinically useful. This is because limitations on sensitivity effectively restrict its application to scientific studies of cohorts, rather than individual patients. Recent improvements in dMRI hardware, acquisition, processing and analysis techniques may, however, overcome these measurement limitations. We therefore acquired the highest-ever angular resolution in vivo tractographic data set, and used these data to ask the question: 'is cutting-edge, optimised dMRI now sensitive enough to measure brain network abnormalities at a level that may enable personalised psychiatry?' The fibre tracking performance of this 'gold standard' data set of 1150 unique directions (11 shells) was compared to a conventional 64-direction protocol (single shell) and a clinically practical, highly optimised and accelerated 9-min protocol of 140 directions (3 shells). Three major tracts of relevance to psychiatry were evaluated: the cingulate bundle, the uncinate fasciculus and the corticospinal tract. We found up to a 34-fold improvement in tracking accuracy using the 1150-direction data set compared to the 64-direction data set, while 140-direction data offered a maximum 17-fold improvement. We also observed between 20 and 50% improvements in tracking efficiency for the 140-direction data set, a finding we then replicated in a normal cohort (n = 53). We found evidence that lower angular resolution data may introduce systematic anatomical biases. These data highlight the imminent potential of dMRI as a clinically meaningful technique at a personalised level, and should inform current practice in clinical studies. 2018 The Author(s).
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Stevens, Michael Charles; Callaghan, Fraser Maurice; Forrest, Paul; Bannon, Paul Gerard; Grieve, Stuart M.Peripheral veno-arterial extra corporeal membrane oxygenation (VA-ECMO) is an established technique for short-to-medium support of patients with severe cardiac failure. However, in patients with concomitant respiratory failure, the residual native circulation will provide deoxygenated blood to the upper body, and may cause differential hypoxemia of the heart and brain. In this paper, we present a general computational framework for the identification of differential hypoxemia risk in VA-ECMO patients. A range of different VA-ECMO patient scenarios for a patient-specific geometry and vascular resistance were simulated using transient computational fluid dynamics simulations, representing a clinically relevant range of values of stroke volume and ECMO flow. For this patient, regardless of ECMO flow rate, left ventricular stroke volumes greater than 28 mL resulted in all aortic arch branch vessels being perfused by poorly-oxygenated systemic blood sourced from the lungs. The brachiocephalic artery perfusion was almost entirely derived from blood from the left ventricle in all scenarios except for those with stroke volumes less than 5 mL. Our model therefore predicted a strong risk of differential hypoxemia in nearly all situations with some residual cardiac function for this combination of patient geometry and vascular resistance. This simulation highlights the potential value of modelling for optimising ECMO design and procedures, and for the practical utility for personalised approaches in the clinical use of ECMO. 2018 Elsevier Ltd
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Stewart, Callum A.C.; Akhavan, Behnam; Santos, Miguel; Hung, Juichien; Hawkins, Clare L.; Bao, Shishan San; Wise, Steven G.; Bilek, Marcela M.M.Biomolecule-functionalization, through the presentation of biological motifs that promote optimal cellular responses, has the capacity to improve the tissue integration of biomedical devices and hence patients quality of life. Radical-functionalized plasma polymer films (rPPFs) readily immobilize bioactive molecules on exposure to a biomolecule-containing aqueous solution without the need for chemical reagents. However, the potential for damage to cells and tissues due to the high local concentration of radicals in freshly deposited radical-functionalized plasma polymer films is of concern. In this study, we compared a fresh (4 h post-deposition) rPPF with one that had been aged for 11 days to explore the effect of the different radical fluxes on cellular responses. Primary osteoblasts and MG63 bone osteosarcoma cells were used to determine whether rPPFs at early aging times exhibited radical-induced cytotoxicity. The aging behavior of the rPPFs demonstrated a connection between the radical decay kinetics and the surface chemistry and wettability. Significant increases in cell attachment and spreading compared to bare Ti were observed for both cell lineages on the rPPF surfaces. The proliferation assays showed equivalent proliferation rates on both the fresh and aged surfaces, and no evidence of cytotoxicity was observed. Overall, we demonstrated that the high flux of radicals emerging to the surface has minimal influence on the biocompatibility of radical-functionalized plasma polymer films. 2018
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Cohen, E. Myfanwy; Farnham, M. M. J.; Kakall, Zohra Mohtat; Kim, Seung Jae; Nedoboy, Polina E.; Pilowsky, Paul M.Respiration and blood pressure are primarily controlled by somatic and autonomic motor neurones, respectively. Central cardiorespiratory control is critical in moment-to-moment survival, but it also has a role in the development and maintenance of chronic pathological conditions such as hypertension. The glial cells of the brain are non-neuronal cells with metabolic, immune, and developmental functions. Recent evidence shows that glia play an active role in supporting and regulating the neuronal circuitry which drives the cardiorespiratory system. Here we will review the activities of two key types of glial cell, microglia and astrocytes, in assisting normal central cardiorespiratory control and in pathology. 2018
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Machaalani, Rita; Ghazavi, Emma; Hinton, Tina; Makris, Angela; Hennessy, AnnemarieIntroduction: Cigarette smoking (CS) and preeclampsia (PE), regulate the expression of nicotinic acetylcholine receptor (nAChR) subunits in the placenta, yet no data exist at the histological level. Methods: Using immunohistochemistry of formalin fixed and paraffin embedded placental tissue, this study quantified the expression of nine nAChR subunits (?2, ?3, ?4, ?5, ?7, ?9, ?1, ?2, ?) and compared the expression amongst four groups of non-smoker non-PE (controls, n = 8), smokers (n = 8), PE (n = 8), and those who were smokers with PE (smoke + PE, n = 4). Quantification was of the percentage of villi with positive cells stained (% villi with +ve), percentage of positive stained cells per villous (% +ve cells/villous), percentage of positive cells in the decidua (%+ve Decidua), and intensity of staining in the outer villous trophoblast layer. Results: Changes were restricted to the villi (as opposed to the decidua), and were specific to the ?9 (smoke + PE), ?1 (smokers), and ?2 (PE) subunits when compared to controls. CS seemed to have a protective effect for the ?2 subunit and an additive effect for the ?9 and ?1 subunits within the villous core/stroma cells and not the trophoblast layer. Discussion: These findings support that both CS and PE affect nAChRs in the placenta, but that this is restricted to the villi. 2018 Elsevier Ltd
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Gatt, Justine Megan; Oakley, Karen L.; Routledge, Kylie M.; Grasby, Katrina L.; Korgaonkar, Mayuresh S.; Grieve, Stuart M.; Schofield, Peter R.; Harris, Anthony W.F.; Clark, Christopher Richard; Williams, Leanne M.Background: Associations between well-being, resilience to trauma and the volume of grey-matter regions involved in affective processing (e.g., threat/reward circuits) are largely unexplored, as are the roles of shared genetic and environmental factors derived from multivariate twin modelling. Methods: This study presents, to our knowledge, the first exploration of well-being and volumes of grey-matter regions involved in affective processing using a region-of-interest, voxel-based approach in 263 healthy adult twins (60% monozygotic pairs, 61% females, mean age 39.69 yr). To examine patterns for resilience (i.e., positive adaptation following adversity), we evaluated associations between the same brain regions and well-being in a trauma-exposed subgroup. Results: We found a correlated effect between increased well-being and reduced grey-matter volume of the pontine nuclei. This association was strongest for individuals with higher resilience to trauma. Multivariate twin modelling suggested that the common variance between the pons volume and well-being scores was due to environmental factors. Limitations: We used a cross-sectional sample; results need to be replicated longitudinally and in a larger sample. Conclusion: Associations with altered grey matter of the pontine nuclei suggest that basic sensory processes, such as arousal, startle, memory consolidation and/or emotional conditioning, may have a role in well-being and resilience. 2018 Joule Inc.
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Lip, Gregory Y.H.; Banerjee, Amitava; Boriani, Giuseppe; Chiang, Chernen; Fargo, Ramiz A.; Freedman, Ben Ben; Lane, Deirdre A.; Ruff, Christian Thomas; Turakhia, Minang P.; Werring, David John; Patel, Sheena; Moores, Lisa K.Background: The risk of stroke is heterogeneous across different groups of patients with atrial fibrillation (AF), being dependent on the presence of various stroke risk factors. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: Systematic literature reviews were conducted to identify relevant articles published from the last formal search perfomed for the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). The overall quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted, voted on, and revised until consensus was reached. Results: For patients with AF without valvular heart disease, including those with paroxysmal AF, who are at low risk of stroke (eg, CHA<inf>2</inf>DS<inf>2</inf>-VASc [congestive heart failure, hypertension, age ? 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)] score of 0 in males or 1 in females), we suggest no antithrombotic therapy. The next step is to consider stroke prevention (ie, oral anticoagulation therapy) for patients with 1 or more non-sex CHA<inf>2</inf>DS<inf>2</inf>-VASc stroke risk factors. For patients with a single non-sex CHA<inf>2</inf>DS<inf>2</inf>-VASc stroke risk factor, we suggest oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel; and for those at high risk of stroke (eg, CHA<inf>2</inf>DS<inf>2</inf>-VASc ? 2 in males or ? 3 in females), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest using a non-vitamin K antagonist oral anticoagulant drug rather than adjusted-dose vitamin K antagonist therapy. With the latter, it is important to aim for good quality anticoagulation control with a time in therapeutic range > 70%. Attention to modifiable bleeding risk factors (eg, uncontrolled BP, labile international normalized ratios, concomitant use of aspirin or nonsteroidal antiinflammatory drugs in an anticoagulated patient, alcohol excess) should be made at each patient contact, and HAS-BLED (hypertension, abnormal renal/liver function [1 point each], stroke, bleeding history or predisposition, labile international normalized ratio, elderly (0.65), drugs/alcohol concomitantly [1 point each]) score used to assess the risk of bleeding where high risk patients (? 3) should be reviewed and followed up more frequently. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF with ?1 non-sex CHA<inf>2</inf>DS<inf>2</inf>-VASc stroke risk factor(s). 2018 American College of Chest Physicians
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Kulkarni, Ketav P.; Hung, Juichien; Fulcher, Alex James; Chan, Alex H.P.; Hong, Andrew; Forsythe, John S.; Aguilar, Marie Isabel; Wise, Steven G.; del Borgo, Mark P.?3-peptides uniquely form shear thinning hydrogels which are proteolytically stable and biocompatible. Herein we describe the synthesis, material and optical characterization of a new class of fluorescently labeled hydrogelators based on a helical N-acetylated ?3-peptide backbone. The resulting hydrogels were analyzed using fluorescence microscopy to confirm successful incorporation of the fluorophore within the fiber matrix without compromising the ?3-peptide self-assembly. Serial, noninvasive conscious animal imaging was used to monitor the injected hydrogel, delivered via subcutaneous injection, while tracking their degradation patterns in real-time. The hydrogels demonstrated persistent, high-intensity fluorescence when monitored over a 14-day period. 2018 American Chemical Society.
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Neubeck, Lis; Freedman, Ben Ben; Lowres, Nicole; Hyun, Karice K.; Orchard, Jessica Joan; Briffa, Tom G.; Bauman, Adrian Ernest; Rogers, Kris D.; Redfern, JulieBackground: Globally, attendance at cardiac rehabilitation (CR) is between 15 and 30%. Alternative models of individualised care are recommended to promote participation in CR, however there has been no prospective testing of different durations of such models. We aimed to replicate the previously proven Choice of Health Options In prevention of Cardiovascular Events (CHOICE) intervention, and to determine if an extended version (CHOICEplus) would confer additional benefits. Methods: Acute coronary syndrome (ACS) survivors not accessing centre-based CR (n = 203) were randomised to CHOICE for 3 months (n = 100) or CHOICEplus for 24 months (n = 103) at four urban hospitals. The program comprised telephone-based tailored risk-factor reduction. Results: CHOICE and CHOICEplus were equivalent demographically and in risk profile at baseline. At 24 months, lipid profiles improved significantly and fewer patients had ?3 risk factors above target compared to baseline in both groups. There were no significant differences between groups. Conclusions: The 24-month CHOICEplus program did not confer additional benefit above the brief 3-month CHOICE intervention. However, participation in either CHOICE and CHOICEplus significantly improved cardiovascular risk profile in ACS survivors. Importantly, the study was feasible, and the intervention translated readily across four hospitals. Overall, this study adds to the existing evidence for brief individualised approaches to CR. 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ)
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Ju, Lining Arnold; McFadyen, James D.; Al-Daher, Saheb; Alwis, Imala D.; Chen, Yunfeng; Tnesen, Lotte L.; Maiocchi, Sophie L.; Coulter, Brianna; Calkin, Anna C.; Felner, Eric I.; Cohen, N. D.; Yuan, Yuping; Schoenwaelder, Simone M.; Cooper, Mark Emmanuel; Zhu, Cheng; Jackson, Shaun P.Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin ?<inf>IIb</inf>?<inf>3</inf> on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion. Analysis of discoid platelet aggregation in the mesenteric circulation of mice confirmed that diabetes leads to a marked enhancement in the formation and stability of discoid platelet aggregates, via a mechanism that is not inhibited by therapeutic doses of aspirin and clopidogrel, but is eliminated by PI 3-kinase inhibition. These studies demonstrate the existence of a compression force sensing mechanism linked to ?<inf>IIb</inf>?<inf>3</inf> adhesive function that leads to a distinct prothrombotic phenotype in diabetes. 2018 The Author(s).
